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Biomedical subjects

A Amato

Publications and source records attributed to A Amato.

At least 37 records · Page 2Linked to original sources

Muon spin relaxation measurements of NaxCoO2.yH2O.

Using the transverse field muon spin relaxation technique, we measure the temperature dependence of the magnetic field penetration depth lambda, in the NaxCoO2.yH(2)O system. We find that lambda, which is determined by the superfluid density n(s) and the effective mass m*, is very small and on the edge of the TF-microSR sensitivity. Nevertheless, the results indicate that this system obeys the Uemura relation. By comparing lambda with the normal state electron density, we conclude that m* of the superconductivity carrier is 70 times larger than the mass of bare electrons. Finally, the order parameter in this system cannot be described by a complete gap over the entire Fermi surface.

Journal Article↗

Distribution and localization of vinculin-talin-integrin system and dystrophin-glycoprotein complex in human skeletal muscle. Immunohistochemical study using confocal laser scanning microscopy.

The vinculin-talin-integrin system and the dystrophin-glycoprotein complex (DGC) are two protein systems with structural and signaling functions, allowing interaction between muscle fibers and extracellular matrix. Although numerous studies have been conducted on these systems, their localization and distribution patterns along the nonjunctional sarcolemma are not clear. On this basis, we carried out an indirect immunofluorescence study on the vastus lateralis muscle of human adults not affected by neuromuscular diseases to better define these patterns. Our results showed that all tested proteins of the two systems have a costameric distribution; all tested proteins of the two systems colocalize with each other (about 90-95% of the cases); only alpha-sarcoglycan in a few cases (about 6%) does not colocalize with other proteins; in about 9-10% of the cases, dystrophin and beta-dystroglycan colocalize partially with other proteins; all tested proteins can be localized in different fibers, both in the region of the sarcolemma over I or A bands. The colocalization between the vinculin-talin-integrin and DGC systems may imply their functional interaction involving the structural aspect, by providing a stronger adhesion between sarcolemma and extracellular matrix in well-defined regions of the muscle fiber. Besides, their colocalization may suggest the existence of a mechanism of mutual modulation of the transmitted signals. This reciprocal control may determine, in different conditions, the prevalence of one system over another with a consequent transmission of different messages to the sarcolemma-associated cytoskeleton.

Dystrophin↗

DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study.

PURPOSE: The aim of this study was to determine TP53 and NM23-H1 immunoreactivity, DNA ploidy, and S-phase fraction (SPF) in a series of 160 patients undergoing resective surgery for primary operable colorectal cancer (CRC) and to establish whether these alterations have any clinical value in predicting CRC patients' prognosis. METHODS: TP53 and NM23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry and DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis. RESULTS: The median follow-up time in our study group was 71 months (range 34-115 months). P53 protein expression was associated with distal tumors (P<0.05) and DNA aneuploid tumors (P<0.05) tumors. DNA-aneuploidy was associated with distal tumors (P<0.01), histological grade (G3) (P<0.05), advanced Dukes' stage (C and D) (P<0.01), lymph node metastases (P<0.01) and high SPF (>18.3%) (P<0.01). The major significant predictors for both disease relapse and death were advanced Dukes' stage, DNA-aneuploidy, and high SPF, while lymphohematic invasion was the only independent factor for relapse and non-curative resection for death. CONCLUSIONS: Our results indicate that DNA aneuploidy and high SPF are associated in CRC with a poor clinical 5-year outcome, while in contrast the prognostic role of TP53 and NM23-H1 expression is still to be clarified.

Adenocarcinoma↗

Sulphydryl groups involved in Na+-Li+ exchange in human erythrocytes.

Oxidative stress causes cellular injury that is thought to be due to increased cytosolic cation levels. Disturbances of a variety of mechanisms which normally maintain intracellular anion/cation homeostasis, occur during oxidative stress. Reactivity of the SH- groups essential for oubain-resistant Na(+)-Li(+) exchange by N-ethylmaleimide (NEM) and selenite was studied in human erythrocytes. In addition, the reactivity of the substances on SH- groups and Li(+) influx have been studied as a function of pH of the medium. The results show that NEM induces an irreversible inhibition of Li(+) influx. It diminishes progressively with the increasing pH of the medium. Whereas we obtain increasing intracellular Li(+) concentration with the rising selenite concentration in the medium. The maximum effect with this substance is reached at about pH 8.0. We can state that the -SH reagents (NEM and selenite) studied behave differently: NEM inhibits Li(+) influx by modifying the essential SH-groups of the membrane proteins in such a way that the exchange is reduced, whereas it maintains the Na(+) permeability almost unaltered. The slight increase in intracellular Na(+) induced by selenite suggests that the oxidative changes in the intracellular sulphydryl groups may constitute an important mechanism for the regulation of the intracellular cations.

Antiporters↗

Sulphate influx in the erythrocytes of normotensive, diabetic and hypertensive patients.

This study aimed to show that modifications in intracellular metabolism are implicated in the pathophysiology of diabetes mellitus and essential hypertension. In fact, total magnesium, calcium, sodium and potassium concentrations, measured in the erythrocytes of normotensive, diabetic and hypertensive patients, have given the following results: a lower intracellular potassium concentration in the erythrocytes of diabetic and hypertensive patients than the erythrocytes of normotensive patients and a more elevated sodium, magnesium, calcium concentrations in the erythrocytes of diabetic and hypertensive patients than the normotensive. Because of the importance of Mg2+ and Ca2+ in metabolic enzyme regulation and their interaction with both Hb and band 3 protein, we examined SO4(2-) kinetic influx in the erythrocytes of normotensive, hypertensive and diabetic patients. The kinetic plots showed different profiles over the three groups and the fluxes were found to be 0.024, 0.061 and 0.072 mmol x (l cells x min)(-1) in normotensive, hypertensive and diabetic patients, respectively. We also found that the Vmax and Km of sulphate influx, obtained by Hofstee plots, increased in the erythrocytes of hypertensive and diabetic patients compared with control cells. In contrast, sulphate influx in the erythrocytes of diabetic and hypertensive patients in the presence of Nifedipine, a calcium antagonist, showed no difference either in the rate constants or in the kinetic profiles, compared to the normotensive control subjects.

Calcium↗

Complications after stapled hemorrhoidectomy: can they be prevented?

Stapled hemorrhoidectomy (SH), a new approach to the treatment of hemorrhoids, removes a circumferential strip of mucosa about four centimeters above the dentate line. A review of 1,107 patients treated with SH from twelve Italian coloproctological centers has revealed a 15% (164/1,107) complication rate. Immediate complications (first week) were: severe pain in 5.0% of all patients, bleeding (4.2%), thrombosis (2.3%), urinary retention (1.5%), anastomotic dehiscence (0.5%), fissure (0.2%), perineal intramural hematoma (0.1%), and submucosal abscess (0.1%). Bleeding was treated surgically in 24%, with Foley insertion 15%; and by epinephrine infiltration in 2%; 53% of patients with bleeding received no treatment and 6% needed transfusion. One patient with anastomotic dehiscence needed pelvic drainage and colostomy formation. The most common complication after 1 week was recurrence of hemorrhoids in 2.3% of patients, severe pain (1.7%), stenosis (0.8%), fissure (0.6%), bleeding (0.5%), skin tag (0.5%), thrombosis (0.4%), papillary hypertrophy (0.3%) fecal urency (0.2%), staples problems (0.2%), gas flatus and fecal incontinence (0.2%), intramural abscess, partial dehiscence, mucosal septum and intussusception (each <0.1%). Recurrent hemorrhoids were treated by ligation in 40% and by Milligan-Morgan procedure in 32%. All hemorrhoidal thromboses were excised. Anal stenoses were treated by dilatation in 55% and by anoplasty in 45%. Fissure was treated by dilatation in 57%. Most complications (65%) occurred after the surgeon had more than 25 case experiences of stapled hemorrhoidectomy. The most common complication in the first 25 cases of the surgeon's experience was bleeding (48%). Even though SH appears to be promising, we feel that a multicenter randomized study with a long-term follow-up comparing SH and banding is necessary before recommending the procedure. Most complications can be avoided by respecting the rectal wall anatomy in the execution of the procedure.

Adult↗

Lectin histochemistry of epidermal glandular cells in the earthworm Lumbricus terrestris (Annelida Oligochaeta).

Carbohydrate residues were localized in the glandular cells of the epidermis of Lumbricus terrestris by lectin histochemistry. The following biotinylated lectins were used: ConA, PNA, WGA, UEA-I. Each lectin has a specific binding pattern in the epidermal glandular cells. The ConA binding is evident in the orthochromatic mucous cells; PNA in the metachromatic mucous cells; WGA in the neuroendocrine-like cells; UEA-I in the cuticle. The epidermal glandular cells possess specific sites for the different lectins in relation to their functional characteristics. Therefore, these sugar residues indicate different behaviours of the cells in epidermal functions related to ion transport, receptor-secretory processes and defence.

Animals↗

Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy.

OBJECTIVE: Mutations in the skeletal muscle gene dysferlin cause two autosomal recessive forms of muscular dystrophy: Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). The purpose of this study was to define the genomic organization of the dysferlin gene and conduct mutational screening and a survey of clinical features in 21 patients with defined molecular defects in the dysferlin gene. METHODS: Genomic organization of the gene was determined by comparing the dysferlin cDNA and genomic sequence in P1-derived artificial chromosomes (PACs) containing the gene. Mutational screening entailed conformational analysis and sequencing of genomic DNA and cDNA. Clinical records of patients with defined dysferlin gene defects were reviewed retrospectively. RESULTS: The dysferlin gene encompasses 55 exons spanning over 150 kb of genomic DNA. Mutational screening revealed nine novel mutations associated with MM. The range of onset in this patient group was narrow with a mean of 19.0 +/- 3.9 years. CONCLUSION: This study confirms that the dysferlin gene is mutated in MM and LGMD2B and extends understanding of the timing of onset of the disease. Knowledge of the genomic organization of the gene will facilitate mutation detection and investigations of the molecular biologic properties of the dysferlin gene.

Adolescent↗

Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication.

PURPOSE: We tested the hypothesis that propionyl-L-carnitine would improve peak walking time in patients with claudication. Secondary aims of the study were to evaluate the effects of propionyl-L-carnitine on claudication onset time, functional status, and safety. SUBJECTS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 155 patients with disabling claudication from the United States (n = 72) or Russia (n = 83) received either placebo or propionyl-L-carnitine (2g/day orally) for 6 months. Subjects were evaluated at baseline and 3 and 6 months after randomization with a graded treadmill protocol at a constant speed of 2 miles per hour, beginning at 0% grade, with increments in the grade of 2% every 2 minutes until maximal symptoms of claudication forced cessation of exercise. Questionnaires were used to determine changes in functional status. RESULTS: At baseline, peak walking time was 331 +/- 171 seconds in the placebo group and 331 +/- 187 seconds in the propionyl-L-carnitine group. After 6 months of treatment, subjects randomly assigned to propionyl-L-carnitine increased their peak walking time by 162 +/- 222 seconds (a 54% increase) as compared with an improvement of 75 +/- 191 seconds (a 25% increase) for those on placebo (P <0.001). Similar improvements were observed for claudication onset time. Propionyl-L-carnitine treatment significantly improved walking distance and walking speed (by the Walking Impairment Questionnaire), and enhanced physical role functioning, reduced bodily pain, and resulted in a better health transition score (by the Medical Outcome Study SF-36 Questionnaire). The incidence of adverse events and study discontinuations were similar in the two treatment groups. CONCLUSIONS: Propionyl-L-carnitine safely improved treadmill exercise performance and enhanced functional status in patients with claudication.

Adult↗

Phase I and pharmacokinetic study of LU79553, a DNA intercalating bisnaphthalimide, in patients with solid malignancies.

PURPOSE: To determine the maximum-tolerated dose and characterize the pharmacokinetic behavior of LU79553, a novel bisnaphthalimide antineoplastic agent, when administered as a daily intravenous infusion for 5 days every 3 weeks. PATIENTS AND METHODS: Patients with advanced solid malignancies received escalating doses of LU79553. Plasma sampling and urine collections were performed on both days 1 and 5 of the first course. RESULTS: Thirty patients received 105 courses of LU79553 at doses ranging from 2 to 24 mg/m(2)/d. Proximal myopathy, erectile dysfunction, and myelosuppression precluded the administration of multiple courses at doses above 18 mg/m(2)/d. These toxicities were intolerable in two of six patients after receiving three courses at the 24-mg/m(2)/d dose level. At the 18-mg/m(2)/d dose, one of six patients developed febrile neutropenia and grade 2 proximal myopathy after three courses of LU79553. The results of electrophysiologic, histopathologic, and ultrastructural studies supported a drug-induced primary myopathic process. A patient with a platinum- and taxane-resistant papillary serous carcinoma of the peritoneum experienced a partial response lasting 22 months. Pharmacokinetics were dose-independent, optimally described by a three-compartment model, and there was modest drug accumulation over the 5 days of treatment. CONCLUSION: Although no dose-limiting events were noted in the first two courses of LU79553, cumulative muscular toxicity precluded repetitive treatment with LU79553 at doses above 18 mg/m(2)/d, which is the recommended dose for subsequent disease-directed evaluations. The preliminary antitumor activity noted is encouraging, but the qualitative and cumulative nature of the principal toxicities, as well as the relatively small number of patients treated repetitively, mandate that rigorous and long-term toxicologic monitoring be performed in subsequent evaluations of this unique agent.

Adult↗

Intravenous L-carnitine increases plasma carnitine, reduces fatigue, and may preserve exercise capacity in hemodialysis patients.

Exercise capacity in patients with end-stage renal disease (ESRD) remains impaired despite correction of anemia. Carnitine insufficiency may contribute to impaired exercise and functional capacities in patients with ESRD. Two randomized placebo-controlled trials were conducted to test whether intravenous L-carnitine improves exercise capacity (assessed by maximal rate of oxygen consumption [VO(2max)]) and quality of life (measured by the Kidney Disease Questionnaire [KDQ]) in patients with ESRD. In study A, patients were administered L-carnitine, 20 mg/kg (n = 28), or placebo (n = 28) intravenously at the conclusion of each thrice-weekly dialysis session for 24 weeks. In study B, a dose-ranging study, patients were administered intravenous L-carnitine, 10 mg/kg (n = 32), 20 mg/kg (n = 30), or 40 mg/kg (n = 32), or placebo (n = 33) as in study A. The prospective primary statistical analysis evaluated changes in VO(2max) in each study and specified that changes in the KDQ were assessed only in the combined populations. L-Carnitine supplementation increased plasma carnitine concentrations, but did not affect VO(2max) in either study. Because change in VO(2max) showed significant heterogeneity, a secondary analysis using a mixture of linear models approach on the combined study populations was performed. L-Carnitine therapy (combined all doses) was associated with a statistically significant smaller deterioration in VO(2max) (-0.88 +/- 0.26 versus -0.05 +/- 0.19 mL/kg/min, placebo versus L-carnitine, respectively; P = 0.009). L-Carnitine significantly improved the fatigue domain of the KDQ after 12 (P = 0.01) and 24 weeks (P = 0.03) of treatment compared with placebo using the primary analysis but did not significantly affect the total score (P = 0.10) or other domains of the instrument (P > 0.11). Carnitine was well tolerated, and no drug-related adverse effects were identified. Intravenous L-carnitine treatment increased plasma carnitine concentrations, improved patient-assessed fatigue, and may prevent the decline in peak exercise capacity in hemodialysis patients. VO(2max) in the primary analysis and other assessed end points were unaffected by carnitine therapy.

Adult↗

Magnetic quantum critical point and superconductivity in UPt3 doped with Pd.

Transverse-field muon spin relaxation measurements have been carried out on the heavy-fermion superconductor UPt (3) doped with small amounts of Pd. We find that the critical Pd concentration for the emergence of the large-moment antiferromagnetic phase is approximately 0.6 at. %Pd. At the same Pd content, superconductivity is completely suppressed. The existence of a magnetic quantum critical point in the phase diagram, which coincides with the critical point for superconductivity, provides evidence for ferromagnetic spin-fluctuation mediated odd-parity superconductivity, which competes with antiferromagnetic order.

Journal Article↗

A 1-year controlled trial of acetyl-l-carnitine in early-onset AD.

OBJECTIVE: To determine the efficacy of acetyl-l-carnitine (ALCAR) on the rate of decline in early-onset AD patients. METHODS: A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were 45 to 65 years old, with a diagnosis of probable AD according to National Institute of Neurological Communicative Disorders-Alzheimer's Disease and Related Disorders Association criteria and had a Mini-Mental State Examination (MMSE) score between 12 and 26. They were treated with ALCAR (1 g tid) or placebo. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive Component and the Clinical Dementia Rating Scale. Secondary measures included the ADAS Non-Cognitive Subscale, the MMSE, an Activities of Daily Living Scale (ADL), and a Clinician-Based Impression of Change (CIBIC). RESULTS: Two-hundred twenty-nine patients were enrolled and randomized to drug treatment, with 117 taking placebo and 112 taking ALCAR. There were no significant differences between the two groups at baseline. For the primary outcome measures, there were no significant differences between the treatment groups on the change from baseline to endpoint in the intent-to-treat analysis. In the completer sample only, there was less deterioration in the MMSE for the ALCAR-treated subjects. There was no difference in rate of decline on the CIBIC and the ADL scale. There were no significant differences in the incidence of adverse events by treatment arm. CONCLUSION: Overall, in a prospectively performed study in young-onset AD patients, ALCAR failed to slow decline. Less decline was seen on the MMSE in the completer sample only, with the difference being mediated by reducing decline in attention. A combination of ALCAR and a cholinesterase inhibitor should be tested for additivity.

Acetylcarnitine↗

Edge restenosis after implantation of high activity (32)P radioactive beta-emitting stents.

BACKGROUND: A high restenosis rate has been reported at the edges ("edge restenosis") of (32)P radioactive stents with an initial activity level of 3 to 12 microCi. This edge effect might be due to balloon injury and to a low dose of radiation at the stent margins. The aim of this study was to evaluate whether the implantation of (32)P radioactive stents with a higher activity level (12 to 21 microCi) combined with a nonaggressive stent implantation strategy could solve the problem of edge restenosis. METHODS AND RESULTS: We compared the results of lesions treated with single radioactive BX stents with an activity of 12 to 21 microCi (group 2, n = 54 lesions) with the results of lesions treated by single radioactive BX stents with an initial activity level of 3 to 12 microCi (group 1, n = 42 lesions). There were no procedural events. At the 6-month follow-up, no myocardial infarctions, deaths, or stent thromboses had occurred. Intrastent binary restenosis was 0% in group 1 versus 4% in group 2 (n = 2, both at the ostium of the right coronary artery, P = NS). Intrastent neointimal hyperplasia was significantly lower in group 2 than in group 1. The intralesion (intrastent plus peri-stent) restenosis rate was 38% in group 1 versus 30% in group 2 (P = NS). Conclusions-Single (32)P radioactive stents with an initial activity level of 12 to 21 microCi reduced intrastent neointimal hyperplasia compared with stents of 3 to 12 microCi, but they did not solve the problem of edge restenosis, even if a nonaggressive stent implantation strategy was used.

Angioplasty, Balloon, Coronary↗

Evidence for a two component magnetic response in UPt3

The magnetic response of the heavy fermion superconductor UPt3 has been investigated on a microscopic scale by muon Knight shift studies. Two distinct and isotropic Knight shifts have been found for the field in the basal plane. While the volume fractions associated with the two Knight shifts are approximately equal at low and high temperatures, they show a dramatic and opposite temperature dependence around T(N). Our results are independent on the precise muon localization site. We conclude that UPt3 is characterized by a two component magnetic response.

Journal Article↗

Euthyroid hyperthyrotropinemia secondary to hyperestrogenemia in a male with congenital adrenal hyperplasia.

A 10-year-old boy with congenital adrenal hyperplasia and associated hyperplastic testicular adrenal rests had high serum concentrations of 17-OH progesterone (17-OHP), estradiol (E2), testosterone (T), and basal and TRH-stimulated TSH and PRL, but normal thyroid hormones (T3, T4, FT3, FT4) and thyroxine-binding globulin (TBG). Upon dexamethasone therapy, steroid hormones returned progressively toward normal as did both PRL and TSH; PRL declined faster than TSH. Serum E2 correlated better with PRL than with TSH. Therefore, the responsiveness of the thyrotrophs to the ambient concentration of E2 is lower and slower than that of the lactotrophs. In the context of the inconclusive data on the role of estrogens in controlling the secretion of TSH in humans, our case suggests that E2 does stimulate the secretion of basal and TRH-elicited both TSH and PRL, and that this positive action is unopposed by T. In contrast, T antagonizes the estrogen-induced increase in serum TBG. We also postulate that E2 might impair the bioactivity of TSH, in order to explain (i) the approximate 3-fold increase in serum TSH coexisting with a normally sized (rather than enlarged) thyroid and normal (rather than increased) serum thyroid hormones, and (ii) the inability of TRH-stimulated TSH to acutely raise FT3 serum levels.

17-alpha-Hydroxyprogesterone↗

Immunohistochemical localization of calcium-binding proteins (CaBPs) in the epidermis of the earthworm Lumbricus terrestris (Annelida, Oligochaeta).

The present immunohistochemical study provides the first evidence of the presence of calcium-binding proteins (CaBPs) in the epidermis of the earthworm Lumbricus terrestris (Annelida, Oligochaeta) a lower invertebrate. The entire epidermis was labelled for calmodulin which is in agreement with its ubiquitous occurrence. Immunopositivity for calbindin D28K was limited to mucous cells, while that for S-100 protein was present only in neuroendocrine-like small granular cells. Finally, labelling for parvalbumin was specifically present in the subcutaneous nerve plexus. S-100 protein is considered to be a marker of neuroendocrine cells, at least in lower invertebrates such as Annelida. Although calbindin D28K is considered to be a marker of these cells in vertebrates, the same function cannot be attributed in Lumbricus terrestris. However, we can conclude that S-100 protein, as a regulatory protein, is phylogenetically older than calbindin D28K. We assume that the latter has an autoregulatory function in secretory processes. In agreement with previous data, we suggest that small granular cells exert a paracrine action in osmoregulatory and secretory processes.

Animals↗