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E Marin

Publications and source records attributed to E Marin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Somatic mutation of human immunoglobulin V genes in the X-linked HyperIgM syndrome.

Somatic mutation of Ig variable regions occurs prominently in germinal centers, but it has been debated whether the mutation process initiates in germinal centers or is activated before germinal center entry of B cells. We have analyzed for the presence of somatic mutation in Ig gene rearrangements of the nonpolymorphic human VH6 gene in the X-linked HyperIgM syndrome, which is associated with defective CD40 ligand expression and absence of germinal centers and generation of memory B lymphocytes. IgM and rare IgG VH6 productive rearrangements were isolated from PBL of patients with X-linked HyperIgM syndrome. Although the majority of both the IgM and IgG VH6 rearrangements had a germline VH6 sequence, 7 of 102 VH6 IgM and 1 of 6 IgG rearrangements had a mutated VH6 gene. The mutation frequency (mutations/bp) was 1.4% with a range of 2-9 mutations per clone, a mutation frequency lower, however, than that observed in IgM (3.2%) and IgG (5.4%) VH6 rearrangements of normal individuals. These results suggest that somatic mutation may be initiated in a CD40 ligand-independent pathway before entry of B cells into germinal centers, but fails to achieve the high mutation frequency observed in the presence of germinal centers.

Amino Acid Sequence↗
PubMed1994

Human splenic IgM immunoglobulin transcripts are mutated at high frequency.

Human spleen immunoglobulin gene rearrangements that used the VH6 gene and were expressed with IgM were characterized for their frequency of somatic hypermutation from PCR amplified spleen cDNA. A high frequency of rearrangements that were somatically mutated was demonstrated by restriction endonuclease analysis and sequencing of cloned rearrangements. The 24 rearrangements cloned from three different spleens had an overall mutation frequency of 3.1% mutations/bp sequenced and ranged from 0.4 to 6.0%. These mutations appeared to have been antigenically selected based on both the high frequency and high amino acid replacement to silent (R/S) ratios in the complementarity determining regions. Five clones that arose from two different rearrangements showed evidence of intraclonal diversification with both shared and unique mutations. The mutated clones of one spleen donor were lower in frequency and were not concentrated in the CDR, which suggested these mutations had not been antigenically selected. These findings support the dissociation of somatic mutation and isotype switching and the possibility that IgM-expressing B cells may serve as human memory B cells.

Amino Acid Sequence↗
PubMed1993

Use of the most JH-proximal human Ig H chain V region gene, VH6, in the expressed immune repertoire.

VH6, the most 3' human H chain V region gene, is preferentially expressed in the preimmune repertoire of the developing human fetus. To determine whether VH6 contributes to the immune repertoire, we amplified and sequenced from human spleen RNA VH6 rearrangements that were isotype-switched to IgG. Eighteen distinct in-frame VH6 clones were sequenced. Definitive assignment to C gamma 1 could be made in the majority of clones, and all had undergone extensive somatic hypermutation in the V region with an average of 14 (range, 2 to 25) mutations/281 bp in the VH6 segment. The overall frequency of somatic mutation was 5.2% of the total nucleotides sequenced. Replacement somatic mutations were targeted to the complementarity determining region, and the complementarity determining region had higher replacement to silent mutation ratios, consistent with antigenic selection. Silent somatic mutations were also significantly more frequent in the complementarity determining region compared to the framework region. Five clones were derived from the same VH6Dxp'1JH6 rearrangement, each containing unique and shared mutations. All DH segments used by independently arising clones were unique, and all DH reading frames were seen. N segments were lacking at either the 5'DH-JH junction or the 3'DH-JH junction in 7 of 13 independent rearrangements. DH-DH recombinations were frequently observed, and there was biased usage of JH3b and JH4b in the clones. The data imply that a high degree of diversity arises from use of this 3'-VH gene in the immune repertoire.

Amino Acid Sequence↗
PubMed1993

Solid organ transplantation: results and implications of acyclovir use in liver transplants.

CMV infection is a major cause of morbidity and mortality following liver transplantation (LT). A prospective study of 218 LT recipients showed that 55% of patients developed CMV infection during the 1st year post-transplantation. Symptomatic CMV infection developed in 25% of all patients, being a major cause of death (21% of all deaths). Of 62 episodes of documented organ invasion, liver was the major site (38 episodes), followed by lung (20), gastrointestinal (4), and retina (4). The main patient group at risk (according to CMV serology of the recipient [(R)/donor(D)]) was the R-/D+: 77% of patients developed CMV infection, all of them with symptoms. The lowest group at risk was the R-/D-: 13% of patients developed CMV infection, half of whom developed symptoms. Time-dependent multivariate statistical analysis of risk factors indicated that the R-/D+ group was the main risk factor for CMV infection (P < .02) and symptomatic infection (P < .0001). To decrease the incidence and severity of CMV infection following LT, a randomized study is ongoing to evaluate the efficacy of ganciclovir (5 mg/kg/IV/q 12 hours for the first 14 days post-LT) followed by acyclovir (800 mg/po/qid for 14 weeks) GCV + ACV (group I), versus acyclovir (same dose for 16 weeks, starting immediately post-LT) ACV (group II). These treatment groups are compared to matched historical controls (C). Preliminary analysis of 83 LT recipients indicates that in group I the median date for the first evidence of CMV infection is delayed (82 days) as compared to group II and C (41 and 33 days, respectively) (P = .004).(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗
PubMed1993

Transposition of the maize autonomous element Activator in transgenic Nicotiana plumbaginifolia plants.

The maize autonomous transposable element Ac was introduced into haploid Nicotiana plumbaginifolia via Agrobacterium tumefaciens transformation of leaf disks. All the regenerated transformants (R0) were diploid and either homozygous or heterozygous for the hygromycin resistance gene used to select primary transformants. The Ac excision frequency was determined using the phenotypic assay of restoration of neomycin phosphotransferase activity and expression of kanamycin resistance among progeny seedlings. Some of the R0 plants segregated kanamycin-resistant seedlings in selfed progeny at a high frequency (34 to 100%) and contained one or more transposed Ac elements. In the primary transformants Ac transposition probably occurred during plant regeneration or early development. Other R0 transformants segregated kanamycin-resistant plants at a low frequency (< or = 4%). Two transformants of this latter class, containing a unique unexcised Ac element, were chosen for further study in the expectation that their kanamycin resistant progeny would result from independent germinal transposition events. Southern blot analysis of 32 kanamycin-resistant plants (R1 or R2), selected after respectively one or two selfings of these primary transformants, showed that 27 had a transposed Ac at a new location and 5 did not have any Ac element. Transposed Ac copy number varied from one to six and almost all transposition events were independent. Southern analysis of the R2 and R3 progeny of these kanamycin-resistant plants showed that Ac continued to transpose during four generations, and its activity increased with its copy number. The frequency of Ac transposition, from different loci, remained low (< or = 7%) from R0 to R3 generations when only one Ac copy was present.(ABSTRACT TRUNCATED AT 250 WORDS)

Agrobacterium tumefaciens↗
PubMed1993

Enzymes of glutathione synthesis in dog skeletal muscles and their response to training.

The glutathione synthesizing enzymes, gamma-glutamyl cysteinyl synthetase and glutathione synthetase, were found in all skeletal muscles studied in dogs. Both occurred also in the liver, but only the former in the lung. The influence of physical training on these enzyme activities was also investigated. For 30 weeks the dogs ran 5 days week-1 on a treadmill at a 15 degrees uphill grade. A 1.5- to 2-fold increase in the gamma-glutamyl cysteinyl synthetase and 3-fold increase in the glutathione synthetase activities was observed in muscles affected by the training procedure (m. triceps, m. extensor carpi radialis and m. gastrocnemius). No training effect could be observed in the splenius and longissimus dorsi muscles or in the liver. The training increased total glutathione levels in the lung and gastrocnemius muscle as well as in the plasma. Glutathione disulfide levels were not altered. Acute physical exercise significantly decreased the plasma total glutathione concentrations in the trained dogs. The results indicate a training responsive adaptation of glutathione system in skeletal muscle.

Animals↗
PubMed1993

Advances in the diagnosis, treatment, and prevention of cytomegalovirus infections after liver transplantation.

CMV is one of the most frequent viral infections after orthotopic liver transplantation. Thus, there should be a high index of clinical suspicion, particularly in liver transplant recipients who have risk factors for the development of CMV disease, including donor CMV seropositivity, the use of antilymphocyte preparations, and retransplantation. The availability of effective antiviral therapy to treat CMV disease has emphasized the importance of an aggressive approach to the early diagnosis and treatment of this viral infection. Ganciclovir has been a major advancement in the treatment of severe CMV disease and has had a major impact on reducing the incidence and severity of CMV disease and its complications in the liver transplant recipient. Furthermore, these antiviral agents are now being evaluated for their prophylactic potential. Indeed, a number of these agents or combinations of these agents have been shown to be effective in reducing the incidence and severity of CMV disease, particularly in the CMV-seropositive transplant recipient; however, the cost-effectiveness of such therapy and its overall impact on long-term graft and patient outcome remain poorly defined at this time. Further investigations will be needed to define the role and importance of prophylactic therapy for the prevention of CMV infection and disease in the liver transplant recipient.

Cytomegalovirus Infections↗
PubMed1992

Interest in and limits to the utilization of reporter genes for the analysis of transcriptional regulation of nitrate reductase.

Reporter gene techniques and mutant analysis were used to identify the molecular basis of the regulation of the expression of nitrate reductase (NR) by nitrate and nitrate-, or ammonium-derived metabolites (N-metabolites), in the true diploïd species Nicotiana plumbaginifolia and in the amphidiploïd species Nicotiana tabacum. The N. plumbaginifolia mutant E23 results from the insertion of a Tnt1-like retrotransposon (Tnp2) in the first exon of the single-copy nia gene, which encodes nitrate reductase. One of the resulting transcripts ends in the 5' LTR (long terminal repeat) sequence of this retrotransposon, and another one in the 3' LTR. Nitrate and N-metabolites modulate the expression of these truncated transcripts, indicating that intron splicing and termination processes are not essential to these regulatory events. A GUS reporter sequence was transcriptionally linked to the promoter of the nia-1 gene of N. tabacum. This fusion was functional in transient expression assays done with protoplasts derived from mesophyll cells of N. tabacum. However none of the regulatory mechanisms known to affect steady-state levels of the nia-1 transcript were operative under these experimental conditions. Transgenic plants carrying either this fusion or translational fusions of GUS linked to the promoter of either the nia-1 or nia-2 gene of N. tabacum were obtained by Agrobacterium-mediated transfer. A low proportion of the transgenic plants (22 out of 105 independent transformants) expressed GUS activity although at a low level. Only 4 plants exhibited a detectable level of GUS mRNA. The concentration of this mRNA increased significantly in an NR-deficient background, indicating regulation by N-metabolites. Only 2 plants, however, showed regulation (induction) by nitrate. Attempts to use aux2 or nptII reporter sequences linked to either the nia-1 or nia-2 promoter as marker genes for the selection of regulatory mutants of the nitrate assimilation pathway were unsuccessful because of our inability to isolate transgenic plants in which these reporter genes were properly regulated by nitrate. The implications of these results are discussed.

Circadian Rhythm↗
PubMed1992

Cardiac fulguration, a new alternative therapy for atrioventricular nodal reentrant tachycardia.

Ten patients underwent endocardial catheter ablation of the atrioventricular junction for atrioventricular nodal reentrant tachycardias. Unipolar cathodic discharges at the distal electrode were administered against an external plate. Bipolar His and atrial deflections showed a mean of 0.15 mv and 0.5 mv respectively. Mean total energy used per patient was 195 J (range: 50-750), with a mean number of ablating discharges of 2.0 per patient, (range: 1-5). Complete atrioventricular block was achieved, but conduction reappeared in all except one patient, after a mean interval of 19.9 min. Electrophysiological evaluation was assessed 3-8 days after ablation. Sustained atrioventricular nodal reentrant tachycardias were no longer inducible in any patient. Retrograde conduction was abolished in six, and was slow and decremental in four. First-degree atrioventricular block, with intranodal delay was diagnosed in six, with an AH interval that ranged from 240 to 130 ms. Mean cycle length for appearance of Wenckebach atrioventricular block was 390 ms after ablation. One patient developed complete atrioventricular block after two discharges of 50 J, another required a repeat ablation for recurrence of intranodal tachycardia and also developed complete anterograde block in a new session of ablation with a 150 J discharge. In these two patients permanent pacing was needed. Eight patients were cured after a mean follow-up of 20 months. Less energy and fewer discharges should be administered to abolish functional dissociation of the atrioventricular node, without complete interruption of anterograde conduction.

Adult↗
PubMed1992

Skeletal muscle and liver glutathione homeostasis in response to training, exercise, and immobilization.

Female beagle dogs were treadmill trained 40 km/day at 5.5-6.8 km/h, 15% upgrade, 5 days/wk for 55 wk. With training, hepatic and red gastrocnemius (RG) total glutathione increased, glutathione peroxidase (GPX) and glutathione reductase (GRD) increased in all the leg muscles studied, and hepatic glutathione S-transferase (GST) activity increased. Joint immobilization (11 wk) did not affect GPX, GRD, and GST of RG, but total glutathione decreased. Male Han Wistar rats were treadmill trained 2 h/day at 2.1 km/h, 5 days/wk for 8 wk. With training, hepatic total glutathione and leg muscle GPX increased but GRD of RG decreased, perhaps because of an increased muscle flavo-protein breakdown during exhaustive training. gamma-Glutamyl transpeptidase was higher in the trained leg muscles. Exhaustive exercise decreased muscle gamma-glutamyl transpeptidase of only control leg muscle, depleted muscle (lesser extent in trained rats) and liver total glutathione of both groups, decreased GRD only in untrained RG, and increased hepatic GST. Endurance training elevated the antioxidant and detoxicant status of muscle and liver, respectively.

Animals↗
PubMed1991

Influence of aging, training and acute physical exercise on plasma glutathione and lipid peroxides in man.

In trained (long-distance runners) and untrained volunteers aged 22 to 57 years, basal plasma glutathione (GSH) concentration decreased significantly with increasing age. In most age groups basal GSH concentration of oxidized glutathione (GSSG) and lipid peroxides (LPO) was not influenced either by age or by training. Following acute physical exercise (bicycle ergometric test), which was maximal for each person and thus different in trained and untrained persons, plasma GSH, GSSG, and LPO concentrations were not changed at all in untrained volunteers. In trained persons, however, GSH concentration was significantly decreased by about 30%. Surprisingly, we observed a decrease in plasma LPO content by about 40%. GSSG content was not altered. The comparison with some physical-physiological parameters indicates that the changes in GSH and LPO concentrations depend on the extent of acute physical exercise rather than on previous training. Alterations of GSH and LPO in plasma could be of physiologic significance.

Adult↗
PubMed1990

Influence of acute physical exercise on glutathione and lipid peroxides in blood of rat and man.

In rats physical exercise (30 min running on a treadmill) lowered total glutathione, oxidized glutathione and lipid peroxide concentration in blood. In man (young healthy male volunteers, moderate to excellent physical condition) running (30 min) did not influence these parameters. It is concluded that by normal life and psychophysical vigilance the moderate oxidative stress could be compensated.

Adult↗
PubMed1981

Effect of carbon source on the accumulation of cytochrome P-450 in the yeast Saccharomyces cerevisiae.

The appearance of cytochrome P-450 in the yeast Saccharomyces cerevisiae depended on the substrate supporting growth. Cytochrome P-450 was apparent in yeast cells grown on a strongly fermentable sugar such as D-glucose, D-fructose or sucrose. When yeast was grown on D-galactose, D-mannose or maltose, where fermentation and respiration occurred concomitantly, cytochrome P-450 was also formed. The cytochrome P-450 concentration was maximal at the beginning of the stationary phase of the culture. Thereafter the concentration decreased, reaching zero at a late-stationary phase. When the yeast was grown on a medium that contained lactose or pentoses (L-arabinose, L-rhamnose, D-ribose and D-xylose), cytochrome P-450 did not occur. When a non-fermentable energy source (glycerol, lactate or ethanol) was used, no cytochrome P-450 was detectable. Transfer of cells from D-glucose medium to ethanol medium caused a slow disappearance of cytochrome P-450, although the amount of the haemoprotein still continued to increase in the control cultures. Cytochrome P-450 appeared thus to accumulate in conditions where the rate of growth was fast and fermentation occurred. Occurrence of this haemoprotein is not necessarily linked, however, with the repression of mitochondrial haemoprotein synthesis.

Aerobiosis↗