Search PubMed⌕ Search

Biomedical subjects

M David

Publications and source records attributed to M David.

At least 433 records · Page 24Linked to original sources

Erythema multiforme-like eruptions associated with etretinate therapy.

Mucocutaneous side-effects from etretinate are common and are usually dose-dependent, whereas hypersensitivity drug eruptions are rare. Two patients are described in whom erythema multiforme-like eruptions appeared several days after oral intake of etretinate. In one patient etretinate rechallenge again produced the skin eruption. A brief review of the less common skin manifestations of etretinate therapy is provided.

Drug Eruptions↗

Rhizobium meliloti fixGHI sequence predicts involvement of a specific cation pump in symbiotic nitrogen fixation.

We present genetic and structural analyses of a fix operon conserved among rhizobia, fixGHI from Rhizobium meliloti. The nucleotide sequence of the operon suggests it may contain a fourth gene, fixS. Adjacent open reading frames of this operon showed an overlap between TGA stop codons and ATG start codons in the form of an ATGA motif suggestive of translational coupling. All four predicted gene products contained probable transmembrane sequences. FixG contained two cysteine clusters typical of iron-sulfur centers and is predicted to be involved in a redox process. FixI was found to be homologous with P-type ATPases, particularly with K+ pumps from Escherichia coli and Streptococcus faecalis but also with eucaryotic Ca2+, Na+/K+, H+/K+, and H+ pumps, which implies that FixI is a pump of a specific cation involved in symbiotic nitrogen fixation. Since prototrophic growth of fixI mutants appeared to be unimpaired, the predicted FixI cation pump probably has a specifically symbiotic function. We suggest that the four proteins FixG, FixH, FixI, and FixS may participate in a membrane-bound complex coupling the FixI cation pump with a redox process catalyzed by FixG.

Adenosine Triphosphatases↗

Rhizobium meliloti regulatory gene fixJ activates transcription of R. meliloti nifA and fixK genes in Escherichia coli.

When present in Escherichia coli on the multicopy expression vector pUC19, a Rhizobium meliloti regulatory gene, fixJ, belonging to a two-component regulatory system, activated the expression of two R. meliloti symbiotic genes, nifA and fixK. Primer extension by reverse transcription showed that FixJ stimulates nifA expression in E. coli by activating pnifA.

Escherichia coli↗

Rearrangements and point mutations of P450c21 genes are distinguished by five restriction endonuclease haplotypes identified by a new probing strategy in 57 families with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is caused by disorders of the P450c21B gene, which, with the P450c21A pseudogene, lies in the HLA locus on chromosome 6. The near identity of nucleotide sequences and endonuclease cleavage sites in these A and B loci makes genetic analysis of this disease difficult. We used a genomic DNA probe that detects the P450c21 genes (A pseudogene, 3.2 kb; B gene, 3.7 kb in Taq I digests) and the 3' flanking DNA not detected with cDNA probes (A pseudogene, 2.4 kb; B gene, 2.5 kb) to examine Southern blots of genomic DNA from 68 patients and 165 unaffected family members in 57 families with CAH. Of 116 CAH-bearing chromosomes, 114 could be sorted into five easily distinguished haplotypes based on blots of DNA digested with Taq I and Bgl II. Haplotype I (76 of 116, 65.6%) was indistinguishable from normal and therefore bore very small lesions, presumably point mutations. Haplotype II (4 of 116, 3.4%) and haplotype III (8 of 116, 6.9%) had deletions and duplications of the P450c21A pseudogene but had structurally intact P450c21B genes presumably bearing point mutations; point mutation thus was the genetic defect in 88 of 116 chromosomes (75.9%). Haplotypes IV and V lack the 3.7-kb Taq I band normally associated with the P450c21B gene. Haplotype IV (13 of 116, 11.2%) retains all other bands, indicating that the P450c21B gene has undergone a gene conversion event, so that it is now also associated with a 3.2-kb band. Haplotype V (13 of 116, 11.2%) lacks the 2.4-kb Taq I fragment and the 12-kb Bgl II fragments normally associated with the P450c21A pseudogene, as well as lacking the 3.7-kb Taq I fragment, indicating deletion of approximately 30 kb of DNA, resulting in a single hybrid P450c21A/B gene. Most (114 of 116, 98%) CAH alleles thus can easily be classified with this new probing strategy, eliminating many ambiguities resulting from probing with cDNA.

Adrenal Hyperplasia, Congenital↗

Gene conversions and rearrangements cause discordance between inheritance of forms of 21-hydroxylase deficiency and HLA types.

Congenital adrenal hyperplasia (CAH) can be caused by a variety of defects in the functional gene encoding 21-hydroxylase (P450c21), which lies in the midst of the human leukocyte antigen (HLA) locus on chromosome 6. As a result, Mendelian genetics permit clinically distinct forms of CAH to be traced genetically by HLA and complement typing of family members. The recent cloning of probes for P450c21 now permits tracing of the affected gene directly. A consanguineous family had three members affected with three clinically distinct forms of CAH. Two of these individuals had identical extended haplotypes, including nine HLA and complement loci. Despite this extensive identity, the patterns of genomic DNA fragments digested with endonuclease EcoRI and detected by a P450c21 cDNA probe differed greatly in these two individuals. Thus, the DNA diagnosis of allelic variation was much more sensitive than the HLA diagnosis. Genomic DNA digested with endonuclease TaqI and probed with P450c21 cDNA revealed the 3.2-kilobase (kb) band, which is generally associated with the nonfunctional P450c21 A pseudogene, in all family members, and also revealed the 3.7-kb band associated with the functional P450c21 B gene in all family members except the severely affected index case. Probing of the same blots with a genomic probe also permitted examination of the adjacent downstream TaqI fragments, showing retention of both the 2.4-kb (A pseudogene) and 2.5-kb (B gene) fragments. Similarly, BglII-digested genomic DNA from all individuals contained both the 12-kb (A pseudogene) and 11-kb (B gene) bands. These data indicate that the basis of 21-hydroxylase deficiency in the index case was due to a homozygous gene conversion event and not to gene deletion. These results show that the DNA in and around the 21-hydroxylase gene is genetically very active, so that the usual generalization concerning linkage and inheritance may yield incorrect conclusions and diagnoses.

Adolescent↗

Perspectives on deafened adults.

A sample of deafened adults in Ontario, Canada provided information about the general course of their adjustment to acquired hearing loss. Their use of counseling services was limited, and those who did use such services expressed dismay about the ignorance surrounding acquired deafness, particularly the assumption that the problems of deafened adults are identical to those of congenitally deaf adults. Four illustrative cases are presented.

Adaptation, Psychological↗

[Immunomodulator treatment of multibacillary leprosy using extracts of microbial ribosomes].

Ribomunyl can in practice be profitably included in the range of immunostimulants, but it requires weekly injections and hence surveillance that will also enable any adverse reactions to be monitored. Its action and tolerance after polychemotherapy have still to be studied. On the basis of our experience, we feel that only isoprinosine, whose effectiveness and good tolerance we have demonstrated, can be used for self-treatment in a mass campaign.

Adjuvants, Immunologic↗

[Value of measuring transcutaneous oxygen pressure in arterial disease of the legs].

The authors specify the methods used for measuring teh transcutaneous oxygen pressure (TcPO2), then present the four main advantages of the TcPO2. 1. Although the decision to amputate remains controlled by the clinical evaluation, TcPO2 is useful when one has to choose to preserve or not the heel support or the knee joint, when hesitating on the indication of amputation or the nature of the pain of a stump. Two measurements are crucial: a value of TcPO2 in a decubitus position greater than 30 mmHg at the amputation level seems to guarantee a primary healing, while under 10 mmHg, failure is the rule. 2. Correlations between the Fontaine classification and TcPO2 measured on the fore-foot in decubitus position, show that, at stages I and II, the TcPO2 is not significantly decreased in comparison with the control group (54 +/- 12 mmHg at stage I, 49 +/- 11 mmHg at stage II) and that at stages III and IV, TcPO2 is significantly much lower than at stages I and II and the value of 10 mmHg seems a remarkable threshold defining severe ischemias (12 +/- 15 mmHg at stage III, 3 +/- 5 mmHg at stage IV). 3. A prospective study of 66 arterial disease of the lower extremities cases, at stages II and IV, validated by a TcPO2 measured at the fore-foot in decubitus position less than 10 mmHg, and which could all benefit from reconstructive arterial surgery, is presented.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Pulmonary and muscular localization of Wegener's granulomatosis. Apropos of a case].

The authors report their observations on a patient presenting with Wegener's granulomatosis with initially isolated pulmonary involvement. Following treatment with a combination of steroid therapy and immunosuppressives muscular involvement developed with specific histological changes. The disease was only controlled by substituting at the same dose prednisone for the methylsulphobenzoate of prednisolone which was prescribed initially; this suggests in equivalent doses the superiority of one product over the other was achieved by a different pharmacodynamic behaviour.

Aged↗

Milk could decrease the bioavailability of 6-mercaptopurine.

The bioavailability of 6-mercaptopurine (6-MP) administered orally for maintenance therapy of children with acute lymphoblastic leukemia is highly variable. Xanthine oxidase (XO) can transform 6-MP into 6-thioxanthine (6-TX) and 6-thiouric acid (6-TUA), which have no therapeutic value. XO is found in high concentration in cow's milk. Incubation at 37 degrees C for 30 min with commercial preparations of pasteurized cow's milk results in transformation of 30% of a clinically relevant concentration of 6-MP into 6-TUA. Milk boiled for 5 min has no effect on the 6-MP. Addition of gastric juice at ratios likely to be seen in children has negligible inhibitory effect on the 6-MP destroying activity of milk. Conversely, folic acid and allopurinol markedly inhibit this effect at clinically relevant concentrations. These observations may help to optimize modalities of administration of 6-MP.

Animals↗

[Familial congenital adrenal hyperplasia caused by 11 beta-hydroxylase. Failure of prevention of sexual ambiguity and prenatal diagnosis].

In a sepharad family from Morocco, 2 children out of 4 had congenital adrenal hyperplasia with 11 beta-hydroxylase deficiency. The index case had a very severe genital masculinization (Prader V), diagnosed at 18 months of age. For the fourth pregnancy, dexamethasone was given from the 8th to the 24th week of amenorrhea, in order to prevent the virilization of a female fetus. The treatment was interrupted for 5 days, at the 20th week, because of amniocentesis. As the amniotic steroid concentrations were normal, the treatment was stopped. Nevertheless the neonate also has severe virilization of the external genitalia and postnatal hormonal studies confirmed the diagnosis of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. The reasons for the failure of the treatment are analyzed.

Adrenal Hyperplasia, Congenital↗

[Nephrocalcinosis and pancreatic calcification after ablation of adrenal adenoma: the role of hypercortisolism?].

Renal and pancreatic calcifications were observed in an infant who had been surgically treated for Cushing's syndrome associated with an adrenal adenoma. On examination of the relation between this secondary complication and Cushing's syndrome, was carried out and the possible role of the post-operative substitutive treatment is discussed. Close echographic surveillance is advocated in these cases.

Adenoma↗