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Biomedical subjects

V Fonseca

Publications and source records attributed to V Fonseca.

At least 19 recordsLinked to original sources
PubMed1992

Gramicidin channels that have no tryptophan residues.

In order to understand how aromatic residues modulate the function of membrane-spanning proteins, we examined the role of the four tryptophans in gramicidin A (gA) in determining the average duration and permeability characteristics of membrane-spanning gramicidin channels; the tryptophan residues were replaced by tyrosine (gramicidin T, gT), tyrosine O-benzyl ether [gramicidin T(Bzl), gT(Bzl)], naphthylalanine (gramicidin N, gN), and phenylalanine (gramicidin M enantiomer, gM-). These analogues form channels with durations and conductances that differ some 10- and 16-fold, respectively. The single-channel conductance was invariably decreased by the Trp----Yyy replacement, and the relative conductance alterations were similar in phosphatidylcholine (DPhPC) and monoglyceride (GMO) bilayers. The duration variations exhibited a more complex pattern, which was quite different in the two membrane environments: in DPhPC bilayers, gN channels have an average duration that is approximately 2-fold longer than that of gA channels; in GMO bilayers, the average duration of gN channels is about one-tenth that of gA channels. The sequence-dependent alterations in channel function do not result from alterations in the channels' peptide backbone structure, because heterodimers can form between the different analogues and gramicidine A, and there is no energetic cost associated with heterodimer formation [cf. Durkin, J. T., Koeppe, R. E., II, & Andersen, O. S. (1990) J. Mol. Biol. 211, 221]. The alterations in permeability properties are consistent with the notion that Trp residues alter the energy profile for ion permeation through long-range electrostatic interactions.

Amino Acid Sequence↗
PubMed1992

Lisinopril and nifedipine administration inhibits the ex vivo uptake of [45Ca2+] by platelets from hypertensive diabetic patients.

1. The effect of administration of the angiotensin converting enzyme inhibitor (ACEI), lisinopril (Carace; 10-40 mg twice daily) and the calcium channel blocker, nifedipine (Adalat Retard; 20-40 mg twice daily) on ex vivo [45Ca2+] uptake by platelets from hypertensive diabetic (type 1 and 2) patients was investigated. 2. At the end of at least 3 months treatment, blood was collected prior to the patient taking the morning dose of medication and washed platelets prepared. [45Ca2+] uptake was monitored following the addition of adrenaline, isoprenaline and dibutyryl cAMP (dbcAMP), as well as in unstimulated (zero) platelets. 3. Both nifedipine and lisinopril significantly inhibited the ex vivo uptake of [45Ca2+] by platelets when this process was stimulated by adrenaline, isoprenaline and dibutyryl cAMP. Basal uptake was also inhibited in both groups. 4. These data consolidate the hypothesis that ACE inhibitors may possess calcium channel/calcium mobilisation blocking properties. Apart from its hypertensive action, lisinopril may also reduce platelet activity via modulation of calcium dynamics, thereby reducing the incidence of vascular complications associated with diabetes mellitus.

Adult↗
PubMed1991

Can urinary thyroid hormone loss cause hypothyroidism?

Four patients presented with nephrotic syndrome associated with hypothyroidism; none had thyroid antibodies. Hypothyroidism resolved on remission of nephrotic syndrome in two patients; thyroxine (T4) replacement was ineffective during periods of gross proteinuria in another, and the fourth had had normal thyroid function a year before presentation. Urinary T4 excretion was measured in ten further patients with proteinuria. It was detectable in the urine in five, who had significantly lower serum free T4 (8.5 [95% confidence interval 5.8-11.2] vs 13.9 [11.1-16.7] pmol/l; p less than 0.01) and free triiodothyronine (3.1 [2.2-4.0] vs 4.9 [3.8-6.0] pmol/l; p less than 0.01) concentrations than the five patients without detectable urinary T4.

Aged↗
PubMed1991

Hypoglycaemia associated with anorexia nervosa.

A 41 year old woman with severe emaciation due to longstanding anorexia nervosa presented with recurrent hypoglycaemia. During an episode of hypoglycaemia, serum insulin and C peptide were undetectable and plasma beta hydroxybutyrate, free fatty acids and lactate were inappropriately low. Response to intravenous glucagon was poor. Muscle enzymes were grossly elevated until she gained weight. Hypoglycaemia was abolished by weight gain.

Adult↗
PubMed1991

Thyrotropin receptor antibodies following treatment with recombinant alpha-interferon in patients with hepatitis.

We measured thyrotropin receptor antibodies in serum obtained from 2 groups of patients participating in clinical trials of recombinant interferon-alpha 2b for viral hepatitis. Group I: Patients with hepatitis B (N = 8), received interferon 5 x 10(6) units thrice weekly for 4 months. Group II: Patients with non-A, non-B hepatitis (N = 16) were randomized to receive interferon in a dose of either 0.25 x 10(6) or 3 x 10(6) U thrice weekly for 6 months and then crossed over to receive the other dosage schedule for a further 6 months. None of the patients developed thyrotoxicosis. Thyrotropin receptor antibody activity was detectable within the "normal range" (less than 10 U/l) in 6 patients prior to treatment. In Group I, thyrotropin receptor antibodies became detectable in 6 patients on treatment, in 4 of whom it was 10 U/l. In Group II, thyrotropin receptor antibody activity was unchanged on low-dose interferon, but on the higher dose became detectable in 9 patients, in 7 of whom it was greater than 10 U/l. We conclude that treatment with interferon is associated with the development of thyrotropin receptor antibodies in a large proportion of patients. It is possible that in some patients treated with higher doses of interferon the increase in thyrotropin receptor antibody activity may be sufficient to induce hyperthyroidism.

Adult↗
PubMed1990

Splenic abscess in patients on hemodialysis.

We describe two patients on hemodialysis who developed staphylococcal splenic abscesses. Both patients previously had staphylococcal septicemia secondary to infection at the dialysis access site. We postulate that access-site infections may predispose hemodialysis patients to splenic abscess, and that these patients should be investigated for a splenic abscess if they should develop unexplained fever.

Abscess↗
PubMed1990

Long term treatment of myasthenia gravis with azathioprine.

Twenty-seven patients with myasthenia gravis have been treated with azathioprine in conjunction with pyridostigmine and prednisolone for a total of 138 patient years. Side effects necessitated discontinuation of treatment in only four patients. Treatment with azathioprine was associated with marked clinical improvement in all the remaining 23 patients, resulting in reduction in the dose of pyridostigmine and prednisolone. The number of hospital admissions as well as the number of episodes of respiratory failure were markedly reduced.

Adult↗
PubMed1990

New treatment approaches to myasthenia gravis.

Myasthenia gravis is an autoimmune disorder in which neuromuscular transmission is impaired by autoantibodies to the acetylcholine receptor (AChR). There are 3 varieties of generalised myasthenia with differing genetic susceptibilities. There is also a purely ocular form in which the weakness is confined to the extraocular muscles, and a neonatal variety which occurs in 20% of babies born to myasthenic mothers due to transplacental passage of the acetylcholine receptor antibody. Another variety of myasthenia occurs several months after treatment with D-penicillamine. The role of the thymus is suggested by abnormal histology in patients with myasthenia and by the beneficial effects of thymectomy in more than two-thirds of patients. Thymectomy is indicated in most patients unless the symptoms are minimal or the weakness is confined to the extraocular muscles. Most patients require treatment with anticholinesterase drugs to prolong the action of acetylcholine at the muscle end-plate. Overdosage of these drugs can provoke a cholinergic weakness. Remissions can be achieved with corticosteroids in 80% of patients. Immunosuppression with azathioprine is used mainly in patients who do not respond to thymectomy or in those patients who are considered unsuitable for operation. Plasma exchange can cause a rapid but temporary improvement in myasthenia, and has no long term place in its treatment.

Female↗
PubMed1988

Platelet aggregation and thromboxane A2 release in primary biliary cirrhosis and effect of D-penicillamine treatment.

Platelet function was assessed in 28 patients with primary biliary cirrhosis (PBC), of whom 10 were receiving D-penicillamine. Patients not on D-penicillamine treatment had platelet aggregation similar to that in the healthy control group; the group treated with D-penicillamine showed significantly enhanced platelet aggregation in response to threshold doses of adrenaline and collagen but not ADP. Median thromboxane B2 production was also higher in D-penicillamine treated patients than in controls or untreated patients; this difference did not reach statistical significance. The addition of D-penicillamine in vitro to platelet rich plasma from normal subjects was shown to enhance adrenaline- and collagen-induced platelet aggregation. Abnormalities of platelet function in PBC patients did not correlate with serum cholesterol concentration or with liver function tests but were related to the stage of disease. The present study emphasises the need to consider the aetiology, disease stage and type of treatment when assessing platelet function and prostanoid release in liver disease.

Aged↗
PubMed1988

Portal hypertension secondary to azathioprine in myasthenia gravis.

A 52 year old man with myasthenia gravis and normal liver function was treated with neostigmine, prednisolone and azathioprine. Three years after starting azathioprine he developed clinical evidence of portal hypertension. A liver biopsy showed nodular regenerative hyperplasia (NRH). The development of NRH following azathioprine treatment in a patient with myasthenia gravis strengthens the case for a causal role of azathioprine in producing NRH and portal hypertension.

Azathioprine↗
PubMed1988

Bone density and cortical thickness in nutritional vitamin D deficiency: effect of secondary hyperparathyroidism.

Measurements of bone mineral index, mean metacarpal cortical thickness, plasma calcium, alkaline phosphatase and serum 25-hydroxyvitamin D and parathyroid hormone concentrations were carried out in 39 Asian vegetarian patients with hypovitaminosis D. It was concluded that PTH is probably the major determinant of osteopenia in patients with osteomalacia and secondary hyperparathyroidism; and that the presence of secondary hyperparathyroidism in association with hypovitaminosis D should be an absolute indication for vitamin D supplementation even in asymptomatic patients.

Adolescent↗
PubMed1988

Fibronectin concentrations in plasma in peripheral vascular disease.

Fibronectin (Fn) concentrations were measured immunoturbidimetrically in plasma of normal subjects and patients with peripheral vascular disease (PVD) before and after venous compression, which caused Fn concentrations to increase in both normal subjects and PVD patients. Basal Fn concentrations and those after 10-min compression were not significantly different in normal subjects and PVD patients. Five minutes after the release of compression, Fn had consistently declined in normal subjects and reverted to baseline values; in contrast, in PVD patients values either increased further or decreased inconsistently. Thus the Fn concentration at 15 min was significantly (P less than 0.001) greater in PVD patients than in normal subjects. Plasma albumin concentrations, measured in parallel to ensure that changes in Fn concentrations were not nonspecific, increased to a greater extent in normal subjects than in PVD patients and reverted to normal after the removal of compression. The Fn/albumin ratio remained unchanged in normal subjects after venous compression, whereas that in PVD patients increased and remained higher, even after decompression. The sustained increase in plasma Fn concentrations and in the Fn/albumin ratio in PVD patients after venous compression may indicate endothelial injury.

Age Factors↗