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Biomedical subjects

L Fernandes

Publications and source records attributed to L Fernandes.

At least 37 records · Page 2Linked to original sources

Complete DNA sequence of yeast chromosome XI.

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome XI has been determined. In addition to a compact arrangement of potential protein coding sequences, the 666,448-base-pair sequence has revealed general chromosome patterns; in particular, alternating regional variations in average base composition correlate with variations in local gene density along the chromosome. Significant discrepancies with the previously published genetic map demonstrate the need for using independent physical mapping criteria.

Base Sequence↗

The yeast YKL741 gene situated on the left arm of chromosome XI codes for a homologue of the human ALD protein.

The yeast gene YKL741 is situated on the left arm of chromosome XI, 12 kb closer to the centromere with respect to the previously localized PAS1 gene. The new yeast gene codes for a homologue of the human ALD protein (ALD: adrenoleukodystrophy). The similarity between the YKL741 protein and the ALD protein is very high in the C-terminal half, which contains an ATP-binding cassette characteristic of the ABC family of transporters. Additionally the YKL741 protein shows some similarity to the ALD protein in the N-terminal half in three putative transmembrane spanning domains. The sequence has been deposited in the EMBL data library under Accession Number X76133 SC YKL.

ATP Binding Cassette Transporter, Subfamily D, Mem↗

DNA inoculation as a novel vaccination method against human retroviruses with rheumatic disease associations.

There are a number of rheumatologic manifestations of human retroviral infections associated with human immunodeficiency virus type I (HIV-I) and the human T-cell leukemia virus type I (HTLV-I) including arthritis, Sjøgren's syndrome-like symptoms as well as other varied autoimmune phenomena. Infection with HTLV-1 may be directly involved in the etiology and/or pathogenesis of an arthritic condition similar to rheumatoid arthritis. We have been characterizing a new vaccination strategy against human retroviral infections, designated DNA inoculation. This procedure involves the intramuscular injection of DNA plasmids which express specific human retroviral antigens. This technique results in the development of humoral and cellular immune responses against these proteins. Specifically, this method has been successfully used to develop immune responses against HIV-I and HTLV-I. The availability of rat and rabbit infection models for HTLV-I, coupled with the successful development of immune responses in these animals after DNA inoculation with an HTLV-I envelope expressing plasmid, will allow the efficacy of this vaccination technique to be evaluated with protection against in vivo viral challenge as an endpoint.

Animals↗

Investigation into the duration of action of sustained-release ibuprofen in osteoarthritis and rheumatoid arthritis.

The duration of action of sustained-release ibuprofen ('Brufen Retard') was investigated in a 14-day double-blind study involving 14 osteoarthritis and 10 rheumatoid arthritis patients. The recommended once-daily dosage of this preparation (1600 mg taken in the evening) provided effective control of arthritic symptoms for both patient groups, with significant overall improvements in pain and stiffness compared to baseline. Substitution of placebo for a single dose of the active treatment resulted in a trend towards worsening of pain and stiffness in the rheumatoid group; however, the only statistically significant change involved impaired quality of sleep (p = 0.03) during the night after placebo administration, over 24-hours after the previous dose of active medication. In this particular study, symptom control was also clearly achieved for the osteoarthritis patients, as this group showed no deterioration within the same period. The 24-hour clinical action underlying these findings is consistent with ibuprofen plasma profiles obtained with the sustained-release preparation in earlier pharmacokinetic studies. It is likely that the greater sensitivity of rheumatoid patients to withdrawal of a single day's active treatment in this study reflects a more severe inflammatory disease process than that of the osteoarthritis patients.

Aged↗

Overexpression of YAP2, coding for a new yAP protein, and YAP1 in Saccharomyces cerevisiae alleviates growth inhibition caused by 1,10-phenanthroline.

A new member of the yeast yAP family, designated YAP2, has been isolated and characterized. The protein displays a high homology with the DNA-binding domain of yAP-1, which contains a basic DNA-binding domain and leucine zipper motif and binds in vitro to the same cis-element. Growth arrest of yeast caused by low concentrations of 1,10-phenanthroline, resulting in zinc and/or iron deprivation, is overcome by over-expression of YAP1 or YAP2. In fact, yeast cells over-expressing YAP1 or YAP2 display pleiotropic drug resistance. On the other hand, a yap2 null mutant has an increased thermotolerance under starvation conditions caused by 1,10-phenanthroline. The latter mutant might become an excellent tool in the study of pathways leading toward thermotolerance acquisition.

Amino Acid Sequence↗

Treatment of polymyalgia rheumatica with intramuscular injections of depot methylprednisolone.

Although the treatment of patients with polymyalgia rheumatica by corticosteroids given by mouth is effective, it is often accompanied by multiple side effects. Various studies have shown that the steroid related complications are proportional to the cumulative dose of steroids administered. In a prospective study of 16 patients with polymyalgia rheumatica the effects of regular intramuscular injections of methylprednisolone over 12 months were evaluated. Remission of disease was achieved with injections of 120 mg of methylprednisolone every three weeks for 12 weeks. Subsequent disease remission was maintained by monthly injections of methylprednisolone on a reducing schedule of dose. The treatment was efficacious, safe, well tolerated over one year, and showed no suppression of the hypothalamic pituitary adrenal axis at 12 weeks after initiation of treatment. Such a mode of steroid treatment results in a considerably lower cumulative steroid dose than with conventional doses of prednisolone given by mouth. These results will be further evaluated in a controlled trial using intramuscular injections of methylprednisolone and prednisolone given by mouth for the treatment of polymyalgia rheumatica.

Delayed-Action Preparations↗

IgA rheumatoid factor and IgG dietary protein antibodies are associated in rheumatoid arthritis.

This study sought to determine whether patients with rheumatoid arthritis (RA) were immunologically sensitised to dietary protein (DP). Using an enzyme linked immunosorbent assay (ELISA), antibodies to milk and wheat proteins were measured in 93 unselected out-patients with classical or definite RA. Of these 93, 53 had raised levels of IgG antibodies to one or both dietary proteins (DP). In the DP antibody positive group, 48 patients (90%) also had raised levels of IgA rheumatoid factor (measured by ELISA) while only 7 (17%) of the 40 DP antibody negative patients had detectable IgA RF; P less than 0.02. There was no association between IgM rheumatoid factor and dietary protein antibodies. These results demonstrate that in RA, raised levels of IgA RF are associated with an increased IgG response to antigens which enter the body through the gastrointestinal tract. A breakdown in gastrointestinal tolerance to dietary antigens may play a role in the immunopathogenesis of RA in these patients who might therefore benefit from dietary manipulation.

Adult↗

Association between villous atrophy in rheumatoid arthritis and a rheumatoid factor and gliadin-specific IgG.

93 patients with rheumatoid arthritis (RA) were examined for histological or other evidence of gut abnormalities. 44 had raised levels of IgG to gliadin, and of these 38 (86%) were also positive for IgA rheumatoid factor (RF). 24 patients (15 with raised levels of IgA RF and wheat protein IgG [AB+] and 9 with normal levels of both antibodies [AB-]) underwent jejunal biopsy. 6 of the AB+ and 1 of the AB- patients had villous atrophy. The AB+ group had lower villous surface/volume ratio and small intestinal lactase concentrations than did the AB- group or age-matched controls. There was no significant difference between the two groups of RA patients in disease severity or treatment regimen. The findings suggest that the gut may play a more important part in the immunopathogenesis of some cases of RA than in others, and that the former may be identified by raised levels of IgA RF and wheat protein IgG.

Adolescent↗

A study of the hypouricaemic effect of tiaprofenic acid.

Tiaprofenic acid is a non-steroidal anti-inflammatory drug which also has hypouriceamic effect. Studies involving 10 healthy volunteers were designed to investigate the mode of this effect. We postulate that the site of action of tiaprofenic acid is at the cell membrane, the mechanism being an interference with the transport of uric acid from intra- to extra-cellular fluid thus limiting its passage into the plasma. The same mechanism acting on renal tubular cells impedes reabsorption thereby increasing uric acid clearance.

Adult↗

The TRH test in rats with chronic Chagas disease.

TRH was studied in rats with chronic Chagas disease. It was found an increased secretion of TSH 60 minutes after intraperitoneal injection of the hypothalamic hormone. T3 and T4 were also decreased in basal conditions. This may indicate a primary hypothyroidism.

Animals↗

Folic acid and lipoprotein lipase from aorta and blood plasma of atherosclerotic rats.

The lipoprotein lipase activity is somehow associated with atherosclerosis, and some publications report a protective effect of this enzyme against infiltration of lipids. In this publication, an atherogenic diet was associated with a decrease of this enzyme in aorta and blood plasma of rats. After administration of folic acid, a significant increase of the clearing factor activity was observed.

Animals↗

Comparison of timegadine and naproxen in rheumatoid arthritis. A placebo controlled trial.

A double blind, cross-over design was used to compare the acute effects of timegadine, naproxen and placebo in rheumatoid arthritis. Timegadine appeared to be more effective than naproxen in those variables related to disease activity although there were no statistically significant differences (apart from morning stiffness) where variables were examined individually. There was a tendency to a rise in alkaline phosphatase, and possibly gamma glutamyl transpeptidase, during the 2-week timegadine treatment period. No other biochemical or haematological abnormality was observed.

Adult↗