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Biomedical subjects

M Marini

Publications and source records attributed to M Marini.

At least 55 records · Page 3Linked to original sources

Neuropeptide degradation in naive and steroid-treated allergic saliva.

The hydrolysis of neuropeptides and possible variations in hydrolysis following steroidal treatment, were examined in the presence of saliva collected from allergic volunteers; data obtained were compared to those obtained with a age and sex-matching group of healthy controls. The results reported indicate the presence of a statistically significant increase in the hydrolysis of the model substrate in allergic as compared to control saliva, and a reduction of substrate hydrolysis in treated as compared to naive allergic saliva. Total enzyme activity, the relative activity of the three classes of substrate-active enzymes (aminopeptidases, dipeptidylaminopeptidases, and dipeptidylcarboxypeptidases), the allergy-associated variations of these activities, and the variations associated to therapy were found to be different in male and female saliva. Specifically, in the controls, the lower level of hydrolysis evident in female as compared to male saliva appeared to be principally induced by lower activity of aminopeptidases. Under allergic conditions, a sex-different increase in the activity of all three classes of substrate-active enzymes modified the hydrolysis pattern differently in samples obtained from male and female donors. Finally, pharmacological treatment induced opposite effects on the enzymes present in each sex: in male saliva, the activity of all three classes of substrate-active enzymes--and, thus, of substrate hydrolysis--was reduced near to the levels measured in the controls. In female saliva, the reduction in the activity of aminopeptidases was coupled with an increase in the activity of dipeptidylaminopeptidases, causing substrate hydrolysis to remain near the levels measured in naive allergic, rather than control, saliva.

Adult↗

DNA endoreplication in the clustered supramedullary neurons of the pufferfish Diodon holacanthus L. (osteichthyes).

DNA contents, ranging from 4C to more than 500C, were determined by a quantitative microfluorimetric assay in supramedullary neuron nuclei of the pufferfish Diodon holacanthus. The distribution of C values after ethidium bromide staining indicates an inter- and intra-individual variation in DNA contents which do not correspond to duplications of the total genome, suggesting that DNA replication is specific for particular genes (endoreplication). Moreover, the DNA content appears to be correlated with nuclear size. A relationship between the DNA amounts and the presence of AT- and GC-rich sequences has been shown. This work demonstrates, for the first time, DNA endoreplication in a specific neuronal type in vertebrates.

Animals↗

Ultrastructural and cytochemical features of the supramedullary neurons of the pufferfish Diodon holacanthus (L.) (Osteichthyes).

Exceptionally high DNA contents were found in supramedullary neuron (SN) nuclei of the pufferfish Diodon holacanthus by quantitative microfluorimetric assay. This phenomenon has been explained by endoreplication, the functional significance of which is still unclear. In this view, the peptidergic nature and large dimensions make the teleostean clustered SN an interesting model for investigating the relationships between endoreplication, nuclear morphology and biosynthetic cellular activity. In this paper, we present a cytochemical and ultrastructural study on the SN of D. holacanthus (Tetraodontiformes). The nucleolar and nucleus structures suggest an intense production of ribosomal components in order to satisfy high cellular demands for protein synthesis. Accordingly, the cytoplasmic compartment presents an extensive rough endoplasmic reticulum, well-developed Golgi apparatus and a remarkable vesicular traffic. These features suggest that SN are engaged in an intense process of protein biosynthesis. The SN are completely surrounded by processes of different types of glial cells. The glial cells may be considered part of the SN cluster.

Acid Phosphatase↗

Elevated circulating levels of monocyte chemoattractant protein-1 in patients with restenosis after coronary angioplasty.

Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant of monocytes; however, its role in the pathophysiology of restenosis is still unclear. We set out to investigate the role of MCP-1 in restenosis after PTCA. In addition, we tested the hypothesis that MCP-1 exerts its effect, at least in part, by inducing O(2)(-) generation in circulating monocytes. Plasma levels of MCP-1 were measured before and 1, 5, 15, and 180 days after PTCA in 50 patients (30 males and 20 females, aged 62+/-5 years) who underwent PTCA and who had repeated angiograms at 6-month follow-up. Restenosis occurred in 14 (28%) patients. The MCP-1 level was no different at baseline between patients with or without restenosis. However, after the procedure, restenotic patients, compared with nonrestenotic patients, had statistically significant (P<0.0001) elevated levels of MCP-1. In contrast, plasma levels of other chemokines, such as RANTES and interleukin-8, did not differ between the 2 groups after PTCA. Higher MCP-1 throughout the study was correlated with restenosis. Moreover, increased MCP-1 was significantly correlated with increased monocyte activity, as reflected by enhanced O(2)(-) generation. Finally, multivariate regression analysis showed that the MCP-1 plasma level measured 15 days after PTCA was the only statistically significant independent predictor of restenosis (beta=0.688, P<0.0001). This study suggests that MCP-1 production and macrophage accumulation in the balloon-injured vessel may play a pivotal role in restenosis after PTCA. MCP-1 may induce luminal renarrowing, at least in part, by inducing O(2)(-) release in monocytes. Further understanding of the mechanism(s) by which MCP-1 is produced and acts after arterial injury may provide insight into therapies to limit the progression of atherosclerosis and restenosis after balloon angioplasty.

Aged↗

New patient-applied therapy for anogenital warts is rated favourably by patients.

Our objective was to determine patient attitudes to having genital warts, and their perceptions of their treatment with imiquimod and other therapies. As an adjunct to a clinical trial in which patients with external genital warts were treated with imiquimod 5% cream until their warts cleared or for up to 16 weeks, quantitative questionnaires consisting of multiple choice questions and 5-point rating scales were completed prior to, and at the end, of the study period. Pre-study and post-study questionnaires were completed by 902 and 629 patients, respectively. Patients expressed a definite concern about genital warts. The majority of patients (70%) had been previously treated for genital warts, and expressed dissatisfaction with their previous therapies. Of patients treated with imiquimod in this study, 82% reported that their warts decreased in size; this occurred within the first 4 weeks for 78% of patients. Sixty-one per cent of patients perceived that their warts completely cleared within the 16-week treatment period. Patients rated imiquimod 5% cream as better than other genital wart therapies in terms of overall satisfaction, time to clearance, convenience and lack of associated pain. In conclusion, patients rated imiquimod 5% cream as an effective treatment which clears warts in an acceptable length of time causing minimal pain and is convenient to use.

Administration, Topical↗

[Arrhythmia risk stratification based on etiological and anatomo-structural factors].

In patients with heart failure, sudden death is very common, particularly in subjects in NYHA functional class II and III (respectively 50-80% and 30-50% of all deaths). The mechanisms at the root of sudden death depend on whether heart failure is secondary to an ischemic or non-ischemic heart disease. In ischemic heart disease, sudden death is mainly arrhythmic (ventricular tachycardia/ventricular fibrillation caused by the reentry circuits in the infarct area or by acute ischemic episodes or bradyarrhythmia). In non-ischemic heart disease, the percentage of arrhythmic sudden deaths seems to be lower. Furthermore, a percentage of sudden death cases with heart failure can be linked to electromechanical dissociation and to pulmonary or systemic embolism. Moreover the risk stratification level differs depending on whether heart failure is caused by an ischemic or a non-ischemic heart disease. The various non-invasive studies mainly employed in patients with ischemic heart disease cannot be reliably used to study patients with non-ischemic heart disease. Even the programmed ventricular stimulation demonstrated prognostic reliability only in cases involving ischemic heart disease. The therapeutic approach may also be conditioned by the heart disease responsible for heart failure. To date, for example, all the studies published on primary prevention of sudden death with an implantable defibrillator have been carried out in patients with ischemic heart disease.

Anti-Arrhythmia Agents↗

Cloning of the cDNAs coding for two novel molybdo-flavoproteins showing high similarity with aldehyde oxidase and xanthine oxidoreductase.

The cDNAs coding for two novel mouse molybdo-flavoproteins, AOH1 and AOH2 (aldehyde oxidase homolog 1 and 2), were isolated. The AOH1 and AOH2 cDNAs code for polypeptides of 1336 amino acids. The two proteins have similar primary structure and show striking amino acid identity with aldehyde oxidase and xanthine oxidoreductase, two other molybdo-flavoenzymes. AOH1 and AOH2 contain consensus sequences for a molybdopterin-binding site and two distinct 2Fe-2S redox centers. In its native conformation, AOH1 has a molecular weight consistent with a homotetrameric structure. Transfection of the AOH1 and AOH2 cDNAs results in the production of proteins with phenanthridine but not hypoxanthine oxidizing activity. Furthermore, the AOH1 protein has benzaldehyde oxidizing activity with electrophoretic characteristics identical to those of a previously identified aldehyde oxidase isoenzyme (Holmes, R. S. (1979) Biochem. Genet. 17, 517-528). The AOH1 transcript is expressed in the hepatocytes of the adult and fetal liver and in spermatogonia. In liver, the AOH1 protein is synthesized in a gender-specific fashion. The expression of AOH2 is limited to keratinized epithelia and the basal layer of the epidermis and hair folliculi. The selective cell and tissue distribution of AOH1 and AOH2 mRNAs is consistent with the localization of the respective protein products.

Aldehyde Oxidase↗

A chromatographic study of the reaction sequence and effect of ligand on the reaction of human hemoglobin with negatively charged isothiocyanates: characterization of an intermediate modified only on the amino termini of the alpha chains.

A HPLC investigation of the reaction of 4-isothiocyanatobenzoic acid and 4-isothiocyanatobenzenesulfonic acid with oxy- and deoxyhemoglobin was carried out. The initial reaction of aromatic isothiocyanato sulfonates and benzoates with either oxy- or deoxyhemoglobin is with the amino termini of the alpha chains followed by a much slower reaction with the amino termini of the beta chains. Both reactions are much faster with deoxyhemoglobin than with oxyhemoglobin. An intermediate reacted only at the termini of the alpha chains with 4-isothiocyanatobenzoic acid was isolated and purified and its functional properties determined. The intermediate showed a reduced oxygen affinity over a wide pH range and a reduced alkaline Bohr effect in the absence of chloride. The oxygen affinity of the intermediate showed a reduced but still significant response to chloride.

Benzenesulfonates↗

Better cognitive and psychopathologic response to donepezil in patients prospectively diagnosed as dementia with Lewy bodies: a preliminary study.

In several retrospective post-mortem studies, patients meeting clinical criteria for Alzheimer's disease (AD) who gained the greatest cognitive benefit from treatment with an acetylcholinesterase (AChE) inhibitor were found to have neocortical Lewy bodies accompanying classical AD neuropathology. This 'dementia with Lewy bodies' (DLB) subtype manifests both parkinsonian and psychopathologic features that set it apart from 'pure' AD (hereafter called AD). In the present preliminary study, 16 dementia patients were prospectively categorized as having DLB versus AD. Subjects were also categorized according to their profile on surface electromyographic (EMG) measures demonstrated in prior work to be analogues of clinically observed parkinsonian extrapyramidal signs (EPS). All patients were prescribed the AChE inhibitor donepezil (5 mg per day). At baseline and at 6 months, patients underwent cognitive testing with the Mini-Mental State Examination (MMSE) while caregivers assessed their psychopathologic status using the Behavioral Symptoms in Alzheimer's Disease (BEHAVE-AD) scale. The tester was blinded to the AD versus DLB classification of the patients. AD cases (N=12) had only a slight increase in cognitive scores, while DLB patients' (N=4) mean MMSE scores increased to a significantly greater degree. Furthermore, patients categorized by EMG as EPS positive (N=8) attained an increase in their mean MMSE score from baseline to 6 months that differed significantly from a decline in MMSE observed among their EPS negative (N=4) counterparts. For all subjects, an increase in MMSE scores across 6 months of treatment correlated with a decline in BEHAVE-AD scores.

Aged↗

Computed tomography of the small bowel in adult celiac disease: the jejunoileal fold pattern reversal.

The aim of this retrospective study was to establish whether the distinctive intestinal fold pattern of celiac disease (CD), known by barium studies as jejunoileal fold pattern reversal (JFPR) may be recognized at CT. The number of intestinal folds per 2.5 cm, seen at CT, were counted in the jejunum and in the ileum of 22 adult patients with CD and compared with the folds of 30 consecutive subjects in whom an intestinal disease had been excluded. The results were submitted to statistical analysis by Student's t-test. In the control group the number of folds per 2.5 cm were 4.88 (SD +/- 0.78) in the jejunum and 2.84 ( +/- 0.62) in the ileum; in the CD group the number of folds were 2.42 ( +/- 1.61) in the jejunum and 5.11 ( +/- 1.24) in the ileum. There was a statistically significant difference in the number of jejunal and ileal folds between the CD patients and the control group (in both cases p < 0.001). The JFPR was seen in 15 patients with CD (68.2 %) but in none of the controls. Our study shows that JFPR is not a normal finding and can be demonstrated by CT in the majority of patients with CD.

Adult↗

Neuropeptide enzyme hydrolysis in human saliva.

The possible hydrolysis of neuropeptides by human saliva was studied using leucine enkephalin as a model. The data obtained indicate that in the presence of saliva this substrate is partially hydrolysed, and that its disappearance corresponds to the appearance of peptides whose composition is consistent with that of the substrate hydrolysis by-products. The formation of these peptides indicates the presence of all three classes of enzymes known to hydrolyse enkephalins in other tissues: aminopeptidases, dipeptidylaminopeptidases and dipeptidylcarboxypeptidases. The activity of these enzymes appears to be altered by the presence of low molecular-weight substances, whose inhibitory activity is apparent on all three classes of enkephalin-degrading enzymes. Substrate degradation was higher in male than female saliva; these differences appear to be caused by lower activity of the enzymes, and higher activity of the low molecular-weight inhibitors, measurable in female as compared to male saliva.

Adult↗

Enkephalin-degrading enzymes and their inhibitors in human saliva.

The possible presence of enzymes able to hydrolyze leucine enkephalin has been investigated in human saliva. The data obtained indicate that, in the presence of saliva, Leu-enkephalin is partially hydrolyzed. The disappearance of the substrate is paired with the formation of hydrolysis byproducts whose composition indicates the presence of all three classes of enzymes known to hydrolyze enkephalins: aminopeptidases, dipeptidylaminopeptidases, and dipeptidylcarboxypeptidases. The presence of low molecular weight substances with inhibitory activity on proteolytic enzymes has also been detected. These substances are active on all three classes of enkephalin-degrading enzymes, although the inhibition is more evident on dipeptidylpeptidases than on aminopeptidases. Substrate degradation was found to be higher in male than in female saliva: this seems to be caused by the activities both of enzymes and low molecular weight inhibitors that are different in the two sexes.

Adult↗

Cytogenetic analysis of the pufferfish Tetraodon fluviatilis (Osteichthyes).

Because of their compact genome, pufferfish (Tetraodontiformes) have been proposed as a model for the study of the vertebrate genome. The genome of pufferfish is peculiar as it has the structural complexity of the genomes of higher vertebrates, but has small introns and lacks large clusters of highly repetitive sequences. Despite such interest, information about the genetics of pufferfish is still scanty. To fill this gap, we have performed a cytogenetic analysis of the pufferfish, Tetraodon fluviatilis, which can be maintained in an aquarium for a long time and, unlike the pufferfish, Fugu rubripes, it is not difficult to obtain. Karyotype analysis shows that T. fluviatilis has 2n = 42 with two metacentric chromosomes, four submetacentrics, two subtelocentrics and 34 acrocentrics. C-banding, followed by DAPI staining, showed that heterochromatin is essentially AT-rich and is located at centromeres. Staining of the same metaphase plates with CMA3 showed the presence of four heterochromatic regions located on two pairs of submetacentric chromosomes. Silver staining and FISH with a 28S rDNA probe showed that these GC-rich regions are nucleolar organizing regions (NORs). Finally, regardless of the technique used, no difference in the chromosome complement was found between males and females.

Animals↗

Clinical feasibility of low energy internal atrial cardioversion with a three-electrode configuration in patients with unsuccessful conventional configurations.

Low energy internal cardioversion is a safe and highly effective method for atrial fibrillation termination. We will describe 6 patients in whom the conventional 2-electrode systems with the defibrillation leads positioned in the right atrium and in the coronary sinus or left pulmonary artery failed to terminate the arrhythmia despite the use of maximal available energies. A 3-electrode configuration including right atrium, coronary sinus and left pulmonary artery was used in order to encompass as much atrial mass as possible between the cathode and the anode. The atrial fibrillation was successfully interrupted in 4 out of 6 patients. The creation of a 3-electrode configuration may be a further technical expedient in order to increase the success rate of internal cardioversion when usual manoeuvres like lead repositioning, reversion of polarity, or addition of antiarrhythmic drugs are ineffective.

Aged↗

Perianal Crohn's disease.

A 13-year-old girl with a history of 4 months of perianal skin lesions is described. Physical examination revealed three 0.5 I 1-cm red, swollen, fleshy, skin tags extending from the perianal area to the perineum (Fig. 1). The patient reported intermittent fever, diarrhea, and abdominal pain, and her body weight was below the third percentile for her age. Laboratory studies showed an erythrocyte sedimentation rate of 101 mm/h; hematocrit of 26%; white blood cell count of 9800/mm3; serum iron of 15 mg/L (normal value (NV), 60-160 mg/L); ferritin of 43.4 microg/L (NV, 12-150 microg/L); transferrin of 203 mg/100 mL (NV, 200-400 mg/100 mL); transferrin saturation of 6% (NV, 20-50%); hypoalbuminemia; negative purified protein derivative (PPD), cytomegalovirus (CMV), human immunodeficiency virus (HIV), venereal disease research laboratory (VDRL), and antinuclear antibody tests; and Toxoplasma titers of 1/16, Van de Kamer 1.67 g/day. A barium examination revealed marked irregularity of the descending colon, and a colonoscopy showed uneven areas of mucosal edema and pseudopolyps in the transverse and descending colon, associated with irregular thickening and stenosis. Histopathologically, large intestine and skin lesions consisted of noncaseating epithelioid and giant cell granulomas (Fig. 2). Cultures for acid-fast bacilli and fungi were negative, and under polarized light no foreign bodies were seen. Treatment with metronidazole (250 mg three times a day), prednisone (0.5 mg/kg/day), and acetylsalicylic acid (75 mg/kg/day) was moderately effective. Vitamin, folic acid, and iron supplements were also added.

Adolescent↗

White cell apoptosis in platelet concentrates.

BACKGROUND: The aim of the present study was the evaluation of the apoptosis in residual white cells (WBCs) contained in platelet concentrates (PCs) and of the relationship of this apoptosis with the concentration of inflammatory cytokines in the medium and with platelet activation. STUDY DESIGN AND METHODS: Three independent methods were used to evaluated apoptosis in WBCs present in 9 PCs, either from single donors by apheresis (SD-PCs) or from pooled buffy coats (BC-PCs). All PCs were divided in two parts, one of which was irradiated. PCs were stored up to 4 days at room temperature, and samples were withdrawn daily for analysis of apoptosis, of platelet activation (surface and soluble CD62P), and of cytokine concentration (interleukin [IL]-1alpha, IL-1beta, IL-6, IL-8, and tumor necrosis factor alpha). RESULTS: Apoptosis was found to occur with storage in both irradiated and nonirradiated units. Platelet activation increased with storage time and was higher in BC-PCs. The amount of released cytokines was rather variable among PC units. Only IL-8 was consistently found to increase with storage time. CONCLUSIONS: Apoptosis of residual WBCs occurred in PC units as a function of storage time. The amount and the time course of apoptosis seem to correlate with IL-8 release rather than with platelet activation or with the occurrence of febrile nonhemolytic transfusion reactions.

Apoptosis↗