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Biomedical subjects

M Munoz

Publications and source records attributed to M Munoz.

At least 37 records · Page 2Linked to original sources
PubMed1998

Outcome of surgery for superior oblique palsy with contracture of ipsilateral superior rectus treated by superior rectus recession.

PURPOSE: To report our experience with this special subgroup of patients with superior oblique palsy. SUBJECTS AND METHODS: All six patients seen since 1990 which the senior author treated who had a unilateral superior oblique palsy accompanied by ipsilateral superior rectus muscle contracture. Surgical management included superior rectus recession along with treatment of the superior oblique palsy by one of several appropriate procedures. RESULTS: Five out of six had an "excellent" surgical outcome defined as no diplopia in primary and reading position, elimination of their abnormal head posture and normalization of versions postoperatively. The sixth patient continued to have a small intermittent vertical deviation, but was functionally satisfactory. CONCLUSIONS: This subset of individuals with superior oblique palsy and ipsilateral rectus contracture can be improved with weakening of the ipsilateral superior rectus as part of the surgical plan.

Adult↗
PubMed1996

Neuropeptide Y and the nonpeptide antagonist BIBP 3226 share an overlapping binding site at the human Y1 receptor.

Neuropeptide Y (NPY) is a 36-amino acid peptide that exhibits actions on the cardiovascular system and the central nervous system. NPY can regulate blood pressure, psychomotor function, anxiety, food intake, and endocrine secretions. BIBP 3226, the first potent and selective nonpeptide antagonist at the NPY Y1 receptor, was designed by mimicking the carboxyl-terminal structure of NPY. We investigated the interaction of NPY and BIBP 3226 with the human Y1 receptor at the molecular level. Alanine mutants at positions Y100, D104, W288, and H298 of the human Y1 receptor showed no or significantly reduced binding for NPY but were not affected in their ability to bind BIBP 3226. Receptors with alanine mutations at positions W163, F173, Q219, N283, F286, and D287 showed reduced binding for both NPY and BIBP 3226. Mutations at other positions were tested (H105, S170, L174, V178, D200, D205, S206, H207, S210, T212, T280, T284, N289, H290, and Q291) and did not affect the binding of NPY or BIBP 3226. The human Y1 receptor mutant Y211A showed no affinity for BIBP 3226 but retained wild-type affinity for NPY. Based on these experimental results, a detailed model for the interaction of BIBP 3226 with the human Y1 receptor was developed using a Y1 receptor model and a three-dimensional model of BIBP 3226. The experimental results, supported by modeling studies, clearly suggest that the native ligand (NPY) and the antagonist (BIBP 3226) share an overlapping binding site.

Amino Acid Sequence↗
PubMed1995

Role of a hydrophobic pocket of the human Y1 neuropeptide Y receptor in ligand binding.

We are investigating the nature of the chemical interactions between the neuropeptide Y (NPY) and its cell surface receptor (Y1). A previous study involving site-directed mutagenesis and computer-aided modelling (Walker et al., 1994) suggested that the C-terminal Tyr36 of NPY, known to be a key residue for receptor binding, might dock at a pocket formed by hydrophobic amino acids of transmembrane domains (TM) 1, 2, 6 and 7 of the Y1 receptor. To investigate which residues were required for ligand binding, we mutated the sequences encoding F41, L43, F96, Y100, F286 and H298 of the human Y1 receptor. The mutant cDNAs were transiently expressed in Hela cells and the ability of the encoded proteins to bind NPY was evaluated. Replacing F41, L43 or F96 with alanines had no effect on NPY binding. On the contrary, Y100, F286 and H298 appeared to be residues critical for ligand binding. In particular, the removal of the hydroxyl group of Y100 (Tyr100-->Phe100 mutation) yielded a protein devoid of affinity for the ligand. The level of expression and the presence on the cell surface of mutants lacking NPY binding activity was assessed by immunological techniques. In addition, we tested the ability of synthetic analogues of neuropeptide Y with substitutions at position 36 to bind to the Y1 receptor. To get spatial insight into the relative positions of the above mentioned residues we constructed a molecular model of the interaction between NPY:Y36 and the elements of the hydrophobic pocket surrounding this residue.

Base Sequence↗
PubMed1995

[Rehabilitation of female urinary incontinence].

Perineal rehabilitation is an appropriate alternative to surgery in the treatment of urinary female incontinence. The most important factors influencing the success of this technique is the ability of the patient to identify correctly the muscles of the pelvic floor, to strengthen this muscles using exercises, electrical stimulation and biofeedback, to contract voluntarily the pelvic floor musculature during stress or sensation of voiding for having a preventive effect on loss of urine, and also to change, if necessary, the micturitional and drinking customs. Some conditions are required to complete a good result: strong motivation of the woman, ability of the physiotherapist or the midwife, quality of care and follow-up of the physician who must clearly know the place of this conservative treatment in selected patients, particularly in moderate stress incontinence, without important prolapse, urge incontinence, pregnancy and post-partum, two conditions in which this technique must have a preventive and curative efficiency.

Female↗
PubMed1995

Serological and genomic characterisation of group A rotaviruses from lambs.

Four lamb rotaviruses were characterised serologically by reactions with monoclonal antibodies and genomically by hybridisation assays and sequencing. Each was found to be distinct. Three viruses belonged to the bovine genogroup and were of subgroup I. These viruses possessed serotypes G3, G6, and G10. Their corresponding P types were P1, P11, and P14 respectively. The only previous isolation of a rotavirus with VP4 of type P14 was also from lambs. The fourth isolate was G9P8, which is the first record of a G9 rotavirus from a species other than man.

Animals↗
PubMed1995

Characterization of the human Y1 neuropeptide Y receptor expressed in insect cells.

We have expressed the human Y1 NPY receptor in insect cells using a recombinant baculovirus (BacY1). Non-linear curve fitting of competition binding data indicates the presence of 500,000-750,000 saturable NPY binding sites per cell. The affinity of the recombinant Y1 receptor for NPY (Kd = 0.38 +/- 0.8 nM) was identical to the natural receptor. We used a foreign epitope to characterize, immunopurify, and localize the recombinant protein. Cross-linking experiments identified a 65 kDa band as the major NPY binding species. Confocal microscopy indicated that although some recombinant proteins are detectable as early as 12 h post-infection, significant expression at the cell surface is only seen 24-48 h post-infection. We also describe a procedure to treat infected Sf21 cells in such a way that they can be frozen and stored at -80 degrees C for many months before being used for binding studies.

Animals↗
PubMed1995

Prevalence of neurological disorders in Haute-Vienne department (Limousin region-France).

The Limousin region had at present one of the largest elderly populations in France and in Europe. To determine the frequency of certain neurological disorders in the elderly, a neuroepidemiological survey was conducted in 1986-1987 on a representative sample of the population in Haute-Vienne (the most population-dense department in the Limousin region). This study used a WHO protocol which was first introduced at the beginning of the 1980s. It had been previously tested in France on a pilot population in 1984. The prevalences of the principal neurological disorders encountered per 100,000 inhabitants were as follows: nonmigraine headache 5,059, migraine 4,270, epilepsy 788, completed stroke 1,445, transient ischemic attacks 657, neuropathy 1,642, Parkinson's disease 328, and dementia 197.

Adolescent↗
PubMed1995

Characteristics of single- and double-stranded RNA synthesis by a rotavirus SA-11 mutant thermosensitive in the RNA polymerase gene.

The phenotype of a rotavirus SA-11 mutant, ts C, which carries a mutation in the gene coding for the viral RNA polymerase was studied in vitro. ts C viral transcription proved to be sensitive to temperature in a different way to that previously described. Like the wild type, the ts C mutant has an optimum for in vitro transcription at 45 degrees, but mRNA synthesis was inhibited at temperatures over 50 degrees. This mutant also showed a higher resistance to transcriptional inhibition by nucleotide analogues than the wild-type strain. The in vitro minus-strand RNA synthesis catalysed by ts C particles indicates that the mutant does not exhibit the expected increased sensitivity to temperatures over 31 degrees shown by the in vivo phenotype. As with plus-strand synthesis, the optimal temperature for the minus-strand synthesis assay was 45 degrees, but for temperatures over 55 degrees, the number of double-stranded RNA products was altered. Our results suggest that when in vitro plus- and minus-strand RNA synthesis in ts C and wild type are compared, the mutated VP1 motif affects both transcription and minus-strand synthesis, but in different ways. In infected cell cultures, the results also show that the phenotype associated with ts C seems to mainly affect the function of plus-strand RNA synthesis.

Animals↗
PubMed1994

Acidic residues in extracellular loops of the human Y1 neuropeptide Y receptor are essential for ligand binding.

To investigate whether negatively charged residues of the human Y1 neuropeptide Y (NPY) receptor are required for ligand binding, a series of mutants were constructed in which aspartic acid and glutamic acid residues present in putative extracellular domains of the Y1 receptor were systematically replaced by alanines. The mutant cDNAs were transiently expressed in HeLa cells using a vaccinia virus-derived expression system, and their ability to bind NPY was evaluated. The level of expression of mutants unable to bind NPY was also tested immunologically. In addition, the ability of the mutant proteins to be recruited to the cell surface was assessed by confocal microscopy. Substitution of aspartic acids and glutamic acids of the N-terminal first extracellular domain had no effect on binding. On the other hand, substitution of acidic residues present in the second, third, and fourth extracellular loops resulted in proteins unable to bind 125I-NPY. These results demonstrate that the extracellular loops of the human Y1 NPY receptor are essential portions of its ligand binding domain.

Amino Acid Sequence↗
PubMed1994

Evaluating the effects of an alpha-2 adrenoceptor antagonist on erectile function in the human male. 1. The erectile response to erotic stimuli in volunteers.

The effects of a new alpha-2 adrenoceptor antagonist on erectile function was assessed in 12 normal volunteers (mean age 28.7, range 20-42), using a double blind, placebo controlled design with two doses of drug and three testing sessions. The drug was administered by intravenous infusion and erectile responses to erotic fantasy and films were monitored by a Rigiscan device. Four effects of the drug were observed; (i) an increase in spontaneous erections; (ii) increased subjective ratings of sexual arousal, before presentation of erotic stimuli; (iii) increased duration of erectile response to erotic stimuli; and (iv) increases in systolic BP and HR both before and during erotic stimulation. These effects were largely restricted to the high dose of the drug. Adverse effects of the drug were minimal.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1994

Evaluating the effects of an alpha-2 adrenoceptor antagonist on erectile function in the human male. 2. The erectile response to erotic stimuli in men with erectile dysfunction, in relation to age and in comparison with normal volunteers.

The effect of a new alpha-2 adrenoceptor antagonist on erectile function was assessed in 24 men with probable psychogenic erectile dysfunction. The drug was given in two dosages, together with placebo, by intravenous infusion in a balanced cross over design. Once plasma levels were established, erectile, subjective and haemodynamic responses to erotic fantasy and films were measured. Subjects were divided into two age groups, "Younger" (i.e. less than 45 years) and "Older" (greater than 45 years). There was a significant though modest increase in the duration of erectile response with the high dose of the drug, but only in the younger men. There were also drug effects on haemodynamic responses confined to the younger men, who showed markedly reduced responses during placebo administration when compared with the older dysfunctional men and with young "functional" volunteers. The findings raise the possibility that in younger men with psychogenic erectile failure, there is an inhibition of general arousal responses to erotic stimuli which is partially reversed by this drug. In the older men, the different pattern of response suggests that a) there may be a decline in response to the drug with age and b) other age-related factors are playing an important part in the aetiology of their erectile failure.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1993

High level expression of human neuropeptide Y receptors in mammalian cells infected with a recombinant vaccinia virus.

Neuropeptide Y (NPY) is a 36 amino acid peptide present in the central and peripheral nervous system. Numerous studies point to a role of NPY in cardiovascular regulation. NPY effects are mediated through stimulation of specific cell surface G protein-coupled receptors. To allow biochemical studies of the receptor and of its interaction with the ligand, we have developed a potent expression system for NPY receptors using a recombinant vaccinia virus. A human NPY receptor cDNA was fused to a strong vaccinia virus promoter and inserted into the viral genome by homologous recombination. Recombinant viruses were isolated and tested for their ability to induce NPY binding site expression following infection of mammalian cell lines. Using saturation and competition binding experiments we measured a Bmax of 5-10 x 10(6) NPY binding sites per cell. The Kd for the binding of NPY is about 20 nM. Labelling of infected cells with a fluorochrome-labelled NPY indicated that the recombinant protein integrates into the cell membrane.

Base Sequence↗
PubMed1991

Erectile response to visual erotic stimuli before and after intracavernosal papaverine, and its relationship to nocturnal penile tumescence and psychometric assessment.

Three methods of assessing erectile capacity--nocturnal penile tumescence (NPT), response to visual erotic stimuli (VES) and to intracavernosal papaverine (ICI)--have been assessed in 42 men presenting with erectile dysfunction. There was some overlap but also important differences between the 3 measures. Subjects were divided into "high" and "low" NPT groups. The "high" group produced greater erectile responses to both VES and ICI. The combination of VES and ICI was the best discriminator of the two NPT groups, and may be of diagnostic value, particularly in younger men, reducing the need for repeated injections and higher doses of papaverine. In the "low" NPT group, presumed predominantly organic, the ICI response correlated better than the VES response with NPT. In the "high" NPT group, the opposite applied, suggesting that in "psychogenic" cases, response to ICI may be modified by psychological mechanisms which could be of aetiological importance and which deserve further study. These three methods should be regarded as measuring different aspects of erectile function and not as alternative diagnostic procedures. More research is required before their respective diagnostic values are established.

Adult↗