Search PubMed⌕ Search

Biomedical subjects

M Leone

Publications and source records attributed to M Leone.

At least 163 records · Page 9Linked to original sources
PubMed1991

Protein dynamics. Comparative investigation on heme-proteins with different physiological roles.

We report the low temperature carbon monoxide recombination kinetics after photolysis and the temperature dependence of the visible absorption spectra of the isolated alpha SH-CO and beta SH-CO subunits from human hemoglobin A in ethylene glycol/water and in glycerol/water mixtures. Kinetic measurements on sperm whale (Physeter catodon) myoglobin and previously published optical spectroscopy data on the latter protein and on human hemoglobin A, in both solvents, (Cordone, L., A. Cupane, M. Leone, E. Vitrano, and D. Bulone. 1988. J. Mol. Biol. 199:312-218) are taken as reference. Low temperature flash photolysis data are analyzed within the multiple substates model proposed by Frauenfelder and co-workers (Austin, R. H., K. W. Beeson, L. Eisenstein, H. Frauenfelder, and I. C. Gunsalus. 1975. Biochemistry. 14:5355-5373). Within this model a distribution of activation enthalpies for ligand binding accounts for the structural heterogeneity of the protein, while the preexponential factor, containing also the entropic contribution to the free energy of the process, is considered to be constant for all conformational substates. Optical spectra are deconvoluted in gaussian components and the temperature dependence of the moments of the resulting bands is analyzed, within the harmonic Frank-Condon approximation, to obtain information on the stereodynamic properties of the heme pocket. The kinetic and spectral parameters thus obtained are found to be protein dependent also with respect to their sensitivity to changes in the composition of the external medium. A close correlation between the kinetic and spectral features is observed for the proteins examined under all experimental conditions studied. The results reported are discussed in terms of differences in the heme pocket structure and in the conformational heterogeneity among the various proteins, as related to their different capability to accommodate constraints imposed by the external medium.

Animals↗
PubMed1991

Short-lasting unilateral neuralgiform headache attacks with tearing and conjunctival injection: the first "symptomatic" case?

A 36-year-old man was suffering from brief, unilateral and short-lasting pain attacks always associated with marked homolateral tearing and conjunctival injection, both presenting in a cluster fashion. An arteriovenous malformation was subsequently discovered in the homolateral cerebellopontine angle. The clinical picture shares similarities with both cluster headache and trigeminal neuralgia, although it can not be accurately placed with either of these forms. Patients with similar symptoms have previously been described in detail, and on the basis of these few descriptions a new syndrome "short-lasting" unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating, and rhinorrhoea has been postulated. Assuming the validity of this syndrome as an entity, this case is in all probability its first "symptomatic" example. Careful evaluation of the varieties of cluster headache and trigeminal neuralgia, and the reporting of similar new cases as they arise are necessary to establish the nosologic boundaries of this syndrome.

Adult↗
PubMed1991

The insulin tolerance test and the ovine corticotrophin-releasing hormone test in episodic cluster headache.

Clinical observations indicate a central nervous system, probably hypothalamic, involvement in cluster headache pathogenesis. In order to investigate the supposed hypothalamic involvement in cluster headache, we followed the hypothalamic-pituitary-adrenal axis and autonomic responses to the insulin tolerance test and the ovine corticotrophin-releasing hormone test in episodic cluster headache patients, both during remission and during the cluster period. The study revealed increased basal cortisol levels in all cluster patients. A blunted cortisol response to ovine corticotrophin-releasing hormone, in spite of a normal ACTH surge, was subsequently found in both illness phases. These findings suggest hypothalamic-pituitary-adrenal axis hyperactivity in both cluster phases. Furthermore, reduced ACTH and cortisol responses after insulin challenge were also observed in both remission and cluster period patients; a reduced norepinephrine surge was seen only in the cluster period. Taken together, these results suggest a hypothalamic involvement in the altered neuroendocrinological and autonomic responses found in our patients.

Adrenocorticotropic Hormone↗
PubMed1991

Immunohistochemical localization of epidermal growth factor receptor in leiomyomas from women treated with goserelin depot.

Epidermal growth factor receptors (EGFr) were studied by immunohistochemistry in human myometrium and leiomyomas from women treated with the GnRH agonist (GnRH-a) goserelin. The results were compared with those obtained from women not treated. Vessel cells of leiomyomas and myometrium were always more immunoreactive than fibrocytes and myocites. In fibroids from treated patients the histochemical score (HSCORE) of vessel cells was always significantly lower (p less than 0.001) than in control patients. Our data confirm a role of EGF also in fibroid growth and suggest that, the blood supply reduction associated with the volume reduction of these tumours, consequent to the GnRH-a treatment, could be EGF mediated.

Adult↗
PubMed1991

Flunarizine in migraine: a minireview.

Flunarizine is a non-selective calcium antagonist. It distributes preferentially in the adipose tissue and passes the blood brain barrier. Numerous controlled clinical studies have established that flunarizine is efficacious in migraine prophylaxis, including double-blind studies in which the drug was compared with placebo or other antimigraine drugs. To avoid side effects a special schedule or administration is necessary. Flunarizine has no myogenic effect on smooth muscle cells of the vessles. It is said to be the only calcium antagonist able to protect brain cells against hypoxic damage. In addition, the considerable body of information which shows flunarizine capable of directly influencing the central nervous system, suggests that the drug's anti-migraine action may depend on its ability to influence central phenomena.

Double-Blind Method↗
PubMed1991

Steroid therapy and the endometrium: biological and clinical implications.

The benefits of estrogen replacement therapy in postmenopausal women include increased quality of life, relief from specific symptoms, and the prevention of osteoporosis, genitourinary atrophy, and cardiovascular diseases. Despite these advantages, this therapy has been reported to be associated with an increased frequency of endometrial hyperplasia and adenocarcinoma. In order to evaluate a possible relationship between the histological findings and stroma-derived growth regulators, 19 endometrial samples obtained from women undergoing both percutaneous (n = 11) and oral (n = 8) steroid replacement therapy were processed for histological and immunocytochemical evaluation of estrogen receptor (Er), progesterone receptor (Pr), and epidermal growth factor receptor (EGFr). Transdermal estradiol was given for 21 days and 10 mg medroxyprogesterone acetate (MAP) were added to the last 12 days; conjugated equine estrogens were given for 21 days and 10 mg MAP added to the last 12 days. Endometrial samples were obtained between days 17-18 of the sixth month of therapy. Proliferative and hyperplastic endometria showed immunoreactivity against Er, Pr, and EGFr. Atrophic endometria were always negative by immunocytochemistry. Our results suggest: 1) a relationship between histological findings and the receptor examined; 2) a crucial role for EGF in the regulation of endometrial proliferation.

Endometrium↗
PubMed1991

Parental sex effect in familial amyotrophic lateral sclerosis.

Since a parental sex effect has been reported in Huntington's disease, we looked to see whether a similar effect is apparent in adult (autosomal dominant) familial ALS. We analyzed the data for 145 patients, with an onset age range of 20 to 68 years and a known affected parent (AP), from 52 families described in the literature. There was a significant increase in the percentage of patients inheriting the gene from an affected mother as a function of the age at onset. There was also a significant correlation between AP and offspring age at onset only when the AP was the mother.

Adult↗
PubMed1990

Oxygen binding to partially oxidized hemoglobin. Analysis in terms of an allosteric model.

We report on oxygen binding to partially oxidized (aquomet) hemoglobin. The fractional saturation with oxygen is evaluated by deconvoluting the optical absorption spectra, in the 500-700 nm wavelength region, in terms of oxyhemoglobin, deoxyhemoglobin and methemoglobin spectral components. Experiments have been performed with auto-oxidized samples and with samples obtained by mixing ferrous hemoglobin with fully oxidized hemoglobin (mixed samples). An increase in oxygen affinity and a decrease in cooperativity are observed on increasing the amount of ferric hemoglobin in the sample. A high cooperativity (nH approximately 2) is maintained even in the presence of 50-60% ferric hemes. Moreover, for equal amounts of methemoglobin the oxygen affinity is lower and the cooperativity higher for mixed samples than for those auto-oxidized. The results are analyzed within the framework of a modified Monod-Wyman-Changeux allosteric model taking into account the effects brought about by the presence of oxidized hemes and of alpha betta dimers. The distribution of ferric subunits within the tetramers in fully deoxygenated and fully oxygenated samples, as derived from the model, provides details on the cooperative behavior of partially oxidized hemoglobin.

Allosteric Regulation↗
PubMed1990

A therapeutic alternative for tension headache in children: treatment and 1-year follow-up results.

Ten young subjects, ranging in age from 12 to 15 years, suffering from tension headache were treated by electromyographic biofeedback (EMG-BFB) twice a week for 12 sessions. The Pain Total Index (PTI) was recorded every month from the beginning to the end of the treatment. At the end of the treatment the PTI decreased significantly in all our patients and, at the same time, the muscular tension values also decreased. This result supports the hypothesis of a correlation between clinical symptom and muscular tension level. We saw our patients for follow-up sessions, and the clinical improvement was confirmed to 1 year from the completion of the treatment; however, the muscular tension values were increased with respect to the last-session values.

Adolescent↗
PubMed1990

Optical absorption spectra of azurin and stellacyanin in glycerol/water and ethylene glycol/water solutions in the temperature range 290-20 K.

We have measured the optical absorption spectra of azurin and stellacyanin in the wavelength range 1100-350 nm and in the temperature interval 290-20 K. Samples are protein aqueous solutions containing 65% (v/v) glycerol or ethylene glycol as cryoprotectants and remain homogeneous and transparent throughout the whole temperature range investigated. Spectra are deconvoluted into Gaussian components and the temperature dependence of the zeroth, first and second moments of the various bands is analyzed, within the harmonic Franck-Condon approximation, to obtain information on the stereodynamic properties of the active sites of these proteins. Sizable differences of the integrated intensities of all the bands with temperature are observed and are attributed to variations of the metal-ligand relative positions (i.e., deformations of the active site) that occur as the temperature is lowered. The mean effective frequency of the nuclear vibrations coupled to all the observed bands is about 150 cm(-1) for both proteins in both solvents used; this indicates that the electronic transitions from which the optical spectrum originates are substantially coupled with low-frequency vibrational modes, likely ligand-metal-ligand deformations. The relevance of the stereodynamic properties of azurin and stellacyanin, investigated in this work, to their functional behavior is also suggested.

Journal Article↗
PubMed1990

Neuroendocrine dysfunction in cluster headache.

Current views on cluster headache pathogenesis indicate a primary central nervous system dysfunction, in particular a hypothalamic involvement. To confirm the hypothalamic involvement in cluster headache we evaluated the hypothalamic-pituitary axis responsiveness with the thyrotrophin releasing hormone (TRH) test. A dose of 200 micrograms of TRH was administered i.v. to nine healthy controls, 32 patients with cluster headache during cluster period and 16 in remission period. Delta maximum thyrotrophin (TSH) was significantly lower in patients with cluster headache during cluster period (p less than 0.05 versus healthy controls and cluster headache patients in remission). No difference was observed between healthy controls and cluster headache patients in remission. A monoaminergic dysfunction at the hypothalamic level is hypothesized.

Adult↗
PubMed1990

The effect of L-acetylcarnitine on some reproductive functions in the oligoasthenospermic rat.

The effect of L-acetylcarnitine (LAC) on some parameters of male reproductive function was studied on rats made oligoasthenospermic with dibromochloropropane (DBCP). DBCP depresses sperm count and motility. After one injection of the drug, LAC induces a recovery of both sperm count and motility but after two injections it is ineffective. This effect is also shown visually by microscopic examination of seminiferous tubules. Among the enzymatic activities evaluated as biochemical markers of testicular function both lactate dehydrogenase and NADPH-cytochrome P 450-reductase increased significantly (P less than 0.05) after treatment with LAC in normal rats. LAC also stimulates testosterone production. It is suggested that LAC may affect testicular function.

Acetylcarnitine↗
PubMed1990

Friedreich's ataxia: a descriptive epidemiological study in an Italian population.

All the cases of Friedreich's ataxia (FA) diagnosed between 1945 through 1984 among residents of a defined area of northwestern Italy were ascertained (N = 59). Cases were diagnosed according to the criteria of the "Quebec Cooperative Study on Friedreich's Ataxia (QCSFA)" with minor modifications. We identified 39 families with 47 probands and 12 secondary cases. Therefore ascertainment probability was 80%. Male to female ratio was 1:1. Pedigrees were compatible with autosomal recessive inheritance. Segregation ratio was 0.28 with both Weinberg's method and the "singles" method (under incomplete ascertainment). Point prevalence ratio was 1.2/100,000 population. Birth incidence rate was 1/36,000 live births. Gene frequency was estimated to be 1/191. The ratio of first-cousin marriages observed among parents of FA patients (3%) was lower than expected from Dahlberg's formula (8%). This finding is not compatible with the hypothesis of genetic heterogeneity for FA.

Adolescent↗
PubMed1990

Is nimodipine useful in migraine prophylaxis? Further considerations.

Nimodipine is one of the most discussed calcium antagonists used in cerebrovascular diseases and, recently, in migraine prophylaxis. Its specificity in preventing cerebral arterial constriction has been invoked to explain nimodipine's efficacy in migraine. The discovery of neuronal receptors specific for dihydropyridines, however, favours a mechanism of action for nimodipine that is not exclusively vascular. This is in accordance with a view of migraine pathogenesis which implicates a primary neuronal event as the basis of the vascular changes observed in migraine patients.

Clinical Trials as Topic↗
PubMed1990

Double blind comparison of lithium and verapamil in cluster headache prophylaxis.

Chronic Cluster Headache (CCH) treatment is troublesome; since there are no pain-free periods, it must be continuous. The most effective CCH prophylactic drug today is lithium carbonate but long-term use of this drug is limited by the possibility of side effects. Recently, calcium antagonists have been successfully employed to prevent migraine, and preliminary studies also indicate that verapamil in particular is an efficacious treatment for CCH. We have conducted a multicenter trial employing a double-dummy, double blind, cross-over protocol, comparing verapamil with the established efficacy of lithium carbonate, in preventing CCH attacks. Both lithium carbonate and verapamil were effective in preventing CCH but verapamil caused fewer side effects and had a shorter latency period. We did not observe any correlation between plasma levels of the two drugs and their clinical efficacy. Both the drugs tested here may exert their effect by restoring a normal inhibitory tone to the pain modulating pathways from the trigemino-vascular system, a circuit putatively implicated in CCH.

Adult↗
PubMed1990

Friedreich ataxia in Italian families: genetic homogeneity and linkage disequilibrium with the marker loci D9S5 and D9S15.

Friedreich ataxia (FA) is an autosomal recessive degenerative disease of the nervous system of unknown biochemical cause. The FA gene has been shown to be in close linkage with the two chromosome 9 markers D9S5 and D9S15, and linkage disequilibrium between FA and D9S15 has been detected in French families by Hanauer et al. We used new highly informative markers at the above loci to analyze Italian FA families for linkage and linkage disequilibrium. The new markers were a three-allele BstXI RFLP at D9S5 (PIC = .55) and a six-allele microsatellite, typed by polymerase chain reaction, at D9S15 (PIC = .75). We obtained maximum lod scores of 8.25 between FA and D9S5, 10.55 between FA and D9S15, and 9.52 between D9S5 and D9S15, all at zero recombination. Our results, combined with those reported by other authors, reduce maxlod-1 (maximum lod score minus 1) confidence limits to less than 1.1 cM between FA and D9S5, 1.2 cM between FA and D9S15, and 1.4 cM between D9S5 and D9S15. Linkage disequilibrium with FA was found only for D9S15 when all families were evaluated but was also found for a D9S5/D9S15 haplotype in a subgroup of southern Italian families. We conclude that FA, D9S5, and D9S15 are tightly clustered and that studies of geographically restricted groups may reveal a limited number of mutations responsible for the disease in the Italian population. We present preliminary evidence from pulsed-field gel electrophoresis that D9S5 and D9S15 may be less than 450 kb apart. Linkage disequilibrium between FA and D9S15 suggests that the disease gene may be at an even shorter distance from this marker locus, which therefore represents a very good starting point for cloning attempts.

Alleles↗
PubMed1989

Patterns of mortality from hereditary ataxias in the United States, 1971 and 1973-1978.

Mortality rates for deaths 'due to' and 'with' hereditary ataxias are presented for the first time. Age-adjusted mortality rates were higher for whites than for nonwhites of either sex, and for men in both racial groups. Age-specific mortality rates for whites showed a peak for 'hereditary spinal ataxia' in the 20-29 age group. For the other types of ataxias they were low until age 40 and increased thereafter. Heart diseases were a frequent cause of death in people dying 'with' hereditary ataxias. The median survival (from birth) for hereditary spinal ataxia in whites was 35 years.

Adolescent↗