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Biomedical subjects

L Bruno

Publications and source records attributed to L Bruno.

At least 55 records · Page 3Linked to original sources

Restoration of polymorphonuclear leukocyte function in elderly subjects by thymomodulin.

Senescence is a specific physiological evolution of human beings associated with a reduction in the functionality of several apparatuses, including the immune system. Thymomodulin (TMD) contains thymus polypeptides (< 10,000 D) and it has been used in a variety of disorders associated with defective immunological functions. The aim of this study was to investigate the effect on polymorphonuclear leukocyte (PMNs) phagocytosis and oxidative burst of a 6-week treatment with 160 mg/day TMD orally in elderly subjects (85.5 +/- 9.7 years). Elderly subjects have impaired PMN phagocytosis and the following release of oxidant radicals. Treatment with TMD for 6 weeks had a restoring effect; phagocytosis and the phagocytic index were significantly improved, with increases of 132.6% and 112.5%. These findings indicate that TMD might be given to enhance the immunodefenses of immunocompromised elderly subjects. Luminol-dependent chemiluminescence was increased by 15.6%, which was not significant, indicating a different response between phagocytosis and release of oxidant radicals.

Aged↗

CD4+8- help prevents rapid deletion of CD8+ cells after a transient response to antigen.

We have followed the fate of mature CD8+ T cells with a male-specific transgenic T cell receptor after antigenic stimulation with hemopoietic cells in the absence or presence of help. Our data show that mature CD8+ T cells can be deleted after a 3-week period of transient activation and that help, e.g. in the form of interleukin-2, can considerably delay the deletion. These experiments have implications for the design of protocols aiming at the establishment of specific immunological tolerance in T cells.

Animals↗

Characterization by yeast artificial chromosome cloning of the linked apolipoprotein(a) and plasminogen genes and identification of the apolipoprotein(a) 5' flanking region.

The apoprotein(a) [apo(a)] gene encodes a protein component of the circulating lipoprotein(a) [Lp(a)]. The apo(a) gene is highly homologous to the plasminogen gene. It encodes one of the most polymorphic human proteins, due to variability in the number of repetitions of structures called kringles. In addition, Lp(a) levels vary among individuals by more than two orders of magnitude, the high levels being highly correlated with predisposition to early atherosclerotic disease. To better understand the genetics and function of the apo(a) gene, we have cloned in yeast artificial chromosome vectors DNA fragments comprising the linked apo(a) and plasminogen genes and other members of the plasminogen family. By a combination of pulsed-field gel electrophoresis and genome walking experiments, we have identified the 5' portion and flanking regions of the apo(a) gene.

Base Sequence↗

Definition of the transcription initiation site of human plasminogen gene in liver and non hepatic cell lines.

We have mapped the cap site of the human plasminogen mRNA by primer extension and PCR techniques and found that it is located at position -161 relative to the first ATG, 97 bases upstream to the 5' end of the previously isolated cDNA clone. Seven human hepatic and non hepatic cell lines and fresh liver cells were tested for human plasminogen mRNA expression: the liver and the liver derived HepG2 cell line represent the major site of plasminogen RNA synthesis while the other cell lines (Hep3B, HeLa, IMR, 293 CaCo and SW626) show much lower levels.

Base Sequence↗

Motility effects of anterior resection of the rectum performed for diverticular disease.

Colonic motility study was performed in fiftyfive patients with symptomatic complicated diverticular disease, who underwent semielective surgery, and in twenty healthy volunteers. The pressure sensors were positioned in the descending and the true sigmoid colon. The colonic motility index was significantly higher in patients with symptomatic complicated diverticular disease than in controls in the basal (p less than 0.001) and post-prandial periods (p less than 0.001). Three months after anterior resection of the rectum with wide resection of descending colon the motility index was significantly reduced (p less than 0.001) in comparison to that before treatment; all patients were asymptomatic. Three years and five years later, the manometric findings continued to be stable and the patients continued to be asymptomatic. These data suggest that anterior resection of the rectum (with wide resection of the descending colon) lowers intraluminal pressure significantly and this effect appears long lasting.

Colon↗

Characteristics of desensitization of insulin secretion in fully in vitro systems.

This report has investigated desensitization of pancreatic B cell secretion, or diminution of the insulin response to chronic stimulation. Freshly isolated rat islets were continuously challenged with various secretagogues over 24 h either in batch incubation or in a computer-controlled, flow-through perifusion system. At various glucose concentrations, secretion rose to a peak level in the third hour, then dropped to a new desensitized secretory level which was 25% or less than that of the maximum rate. The amount of insulin secreted was glucose dependent although secretory kinetics were independent of the amount of hormone secreted. At all glucose concentrations the reduction in islet insulin content was not great enough to account for the observed degree of desensitization. Furthermore at hour 20, islets responded vigorously to an alternate stimulus, indicating insulin stores and islet secretory machinery were still capable of being stimulated. Addition of 3-isobutyl-1-methylxanthine or forskolin did not prevent glucose-induced desensitization. Insulin secretion desensitized similarly to nonglucose (alpha-ketoisocaproic acid) and nonfuel (phorbol ester) stimuli. Glucose potentiation of a terminal KIC response, although demonstrable after 20 h of chronic glucose, was diminished somewhat compared to that after 3 h of chronic glucose. Delaying glucose stimulation by 6 h reduced insulin secretion, yet desensitization persisted. Although insulin secretion entrained to a glucose signal which oscillated from 1.3-12.7 mM in sine wave pulses of 90-min frequency, desensitization was not prevented. Thus, desensitization occurred in response to glucose, nonglucose, and nonfuel stimuli and despite delayed or oscillating signals. We conclude that exhaustion of a finite insulin compartment is not the underlying defect in desensitized secretion and suggest that metabolic feedback or recruitment of multiple heterogeneous compartments may explain this phenomenon.

1-Methyl-3-isobutylxanthine↗

Periodic spasms: an unclassified type of epileptic seizure in childhood.

Seven boys aged between 14 months and 13 years with focal or multifocal partial epilepsy had very unusual seizures, characterized by series of periodic bilateral spasms. These consisted of a brief, complex movement of slight to severe intensity, mainly involving the axial muscles, with raising of the shoulders, adversion of the eyes and head, often with rictus-type facial grimaces and occasional stretching of the legs and emission of a guttural sound. The ictal EEG showed a pattern of periodic complexes, characterized by a slow wave with superimposed fast activity. This form of epileptic seizure is resistant to treatment and is found only in patients affected by a brain disease consisting of a fixed or progressive encephalopathy. These observations document the existence of a rare form of seizure or epileptic event, not yet included in the International Classification of epileptic seizures and clinically relevant because of its diagnostic and prognostic implications.

Adolescent↗

The effect of the thromboxane synthetase inhibitor Dazmegrel (UK-38,485) on wound healing, dermal ink perfusion and skin blood flow measurements in deep partial thickness burns.

A guinea-pig model was used to evaluate the effect of Dazmegrel (UK-38,485), a new highly selective inhibitor of thromboxane synthetase, on burn wound healing. Dazmegrel had a beneficial effect on wound healing when given systemically at a dosage of 3.4 mg kg-1 day-1 but higher doses had no effect. There was no change in dermal perfusion measured by India ink injection or by 133Xe injection in any of the groups receiving parenteral Dazmegrel. Neither was the number of hair follicles in the healing burn wound significantly different between the treated and control animals. When Dazmegrel was applied topically, it inhibited wound healing. These findings are consistent with previous reports from different laboratories that prostaglandin inhibitors impair healing of the burn wound when applied topically but improve wound healing when given parenterally. The present study further suggested that the improvement in wound healing in this model was not mediated by improved dermal perfusion.

Administration, Topical↗

Diagnostic and surgical management of patients with aneurysms of the thoracic aorta with various causes. Echocardiography and contrast enhanced computed tomography in prophylactic replacement of the ascending aorta.

Sixty eight patients with aneurysms of the thoracic aorta were studied. Forty one had aortic dissection, 24 had dilatation only, and three had transverse aortic rupture. Sixteen had Marfan's syndrome; 17 had hypertension; and in eight there were other causal factors. In 17 the cause of the aneurysm was unknown. Histological examination did not help to establish the cause of aneurysm. Echocardiography failed to detect dissection of the ascending aorta in four (21%) out of 19 cases studied. The mortality rate in the whole series was 26%. Early (operative and hospital) and late deaths occurred in 20% and 6% of patients respectively. The early mortality rate was 40% in the 24 emergency cases of dissection of the ascending aorta, 9% in patients operated on for dilatation of the ascending and transverse aorta without dissection, and 8% in patients with chronic dissection of the ascending aorta who had elective operation. Early and late mortality rates were no higher in patients with Marfan's disease than in any of the other groups. It is suggested that contrast enhanced computer tomography should be performed in all patients with pronounced aortic root dilatation and in patients with Marfan's disease with symptoms which suggest dissection, even if they have only slight aortic root dilatation. Preventive replacement of the ascending aorta should be considered in more patients to reduce the number of emergency operations, in which the mortality rate is high. There is no definite limit of aortic root dilatation above which preventive replacement of the ascending aorta should be routinely considered.

Adolescent↗

[Effect of tiropramide chlorhydrate on intestinal transit time in patients with irritable colon syndrome].

The effect of tiropramide hydrochloride--a new spasmolytic drug with calmodulin-independent activity--in correcting alterations of intestinal transit, has been investigated in 40 IBS patients (20 with accelerated and 20 with delayed transit time). Intestinal transit has been evaluated by means of radioopaque markers. Tiropramide hydrochloride, at a dose of 100 mg t.i.d. for 4 weeks, was found significantly more effective than placebo both in normalizing intestinal transit time and in inducing symptomatic relief.

Adult↗

Cardiac, skeletal, and ocular abnormalities in patients with Marfan's syndrome and in their relatives. Comparison with the cardiac abnormalities in patients with kyphoscoliosis.

Polygraphic (including apexcardiograms and carotid pulse tracings) and M mode echocardiographic examinations were carried out in 34 symptomatic patients with Marfan's syndrome; similar studies were performed in 32 relatives and in 34 young patients with kyphoscoliotic disease. The purpose of these investigations was to determine the association between cardiac and oculoskeletal abnormalities and to identify specific patterns of disease with a poor prognosis. Polygraphic tests showed significant changes in all patients with Marfan's syndrome: 74% showed the apical systolic click and murmur of mitral valve prolapse; 48% had the diastolic murmur of aortic regurgitation; isolated mitral valve prolapse was found in 52%, 26% had isolated aortic regurgitation, and 22% had a combination of the two. Echocardiographic changes were also found in all patients: 79% had aortic root dilatation; 48% fluttering of the anterior mitral leaflet; 79% mitral valve prolapse, mostly pansystolic; 34% both mitral prolapse and aortic root dilatation; and 34% left ventricular dilatation. The severities of the cardiac and oculoskeletal abnormalities were not correlated. The high prevalence of mitral valve prolapse found in these patients, which did not vary with age or sex, was also present in their relatives: mitral prolapse was present in 38% and aortic dilatation, with or without regurgitation, in 14%. Four of the relatives had clearcut Marfan's syndrome, and at least four others a forme fruste. The metacarpal index was abnormal in 41% of the relatives; ocular abnormalities were rare. In kyphoscoliotic patients only an increase in the prevalence of mitral prolapse (18.2% in women, none in men) was found. These findings underline a complex pattern of association between cardiac, ocular, and skeletal abnormalities in patients with Marfan's syndrome and confirm an appreciable inheritability of several of the markers of the disease.

Adolescent↗

An animal model to detect learning deficits following treatment of the immature brain. Studies using radiation and methotrexate.

Learning deficits have been noted in children with acute leukemia given methotrexate (MTX) with and without cranial irradiation (RT) for prophylaxis. A rat model has been developed to assess treatment effects on learning. The test used was altered performance of a simultaneous discrimination task in a standard operant conditioning box, employing the mean number of days needed to score 80% correct responses as the criterion. An illustrative experiment distributed suckling rats among four groups: (1) 36 controls; (2) 14 cranial RT (1,000 R); (3) 14 MTX (5 mg/kg i.p.); (4) 36 RT + MTX 24 h later, and (5) 12 undernourished controls (to match poor weight gain patterns of treated animals). Survivors were tested 10-12 weeks later: values for groups 1-5 in order were 3.9, 4.1, 4.7, 5.0 and 4.0 days. Only group 4 results were significantly different from group 1 (p = less than 0.05).

Age Factors↗

[Mycological diagnosis and study of mycetes isolated from an area along the Tyrrhenian coast in the province of Catanzaro (Calabria)].

10 areas along the Tyrrhenian coast were studied: 37 genera of hyphomycetes were isolated from 100 sand samples. The genera Aspergillus, Fusarium, Alternaria, Penicillium, Dendryphiopsis, were constantly present. Many of the fungi isolated occurred only rarely and were represented by Trichoderma, Sepedonium, Cladosporium and Chrysosporium. The genus Geotrichum was the most prevalent of the unpigmented yeasts which were predominant (59.6%), while Rhodotorula was the main genus in pink yeasts (40.4%). The species Chrysosporium keratinophilum and Chrysosporium tropicum were the only representatives of keratinophilic fungi; Dermatophytes were not isolated. Furthermore the hyphomycetes were osmophilic genera and for this reason they may be regarded as specific sand flora. Hence the data proves useful to us, indicating the negligible degree of human and animal influence of these sea shores.

Dermatomycoses↗