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Biomedical subjects

A Bruni

Publications and source records attributed to A Bruni.

At least 37 records · Page 2Linked to original sources

Alterations in spore production in Trichophyton rubrum treated in vitro with 1-amino-6-methyl-4-phenylpyrazolo[3,4-d]-1,2,3-triazole.

The effects of the newly synthesized triazole, 1-amino-6-methyl-4-phenylpyrazolo[3,4-d]-1,2,3-triazole (V5), on the dermatophyte Trichophyton rubrum were tested. Optical and electron microscopy showed that the treatment suppressed the various forms of saprophytic conidia, induced the formation of chlamydospores and accelerated the formation of arthroconidia. This new triazole did not reveal any fungistatic or fungicidal activity and could not be considered as an antifungal substance.

Antifungal Agents↗

DNA ploidy pattern in papillary renal cell carcinoma. Correlation with clinicopathological parameters and survival.

Papillary renal cell carcinoma (PRCC) is a less frequent histomorphologic variant of renal cortical carcinoma (RCC). Morphologically, PRCC differs from other forms of RCC in that it is associated with frequent tumor infiltration by macrophages and lymphocytes, and a tendency for central necrosis and cystic change. Follow-up data revealed that survival rates are higher among patients with PRCC than among patients with other forms of RCC. The authors explore the DNA content in a series of PRCC and correlate the findings with nuclear grade, pathological stage and survival. Using Flow Cytometry, we analysed the DNA ploidy pattern of 37 paraffin-embedded PRCC. At least 3 tumor fragments were analysed in each case. To obtain the reference diploid standard, the non-tumor renal tissue from the same case was added to the solution. Tumor ploidy was classified as diploid and aneuploid. The degree of DNA content abnormalities was given by the DNA Index (DI). An aneuploid DNA profile was found in 65% of the tumors. 25% of the aneuploid tumors presented near diploid peaks (1.10 < DI < 1.30; low degree aneuploidy), 25% were hyperdiploid, while 22% had a hypodiploid profile (DI < 0.90). A homogeneous DNA ploidy pattern was observed in 25 tumors (68%), while there was intratumoral heterogeneity in 12 tumors (32%). Patients with aneuploid DNA patterns had high grade/stage tumors and died at the end of the follow-up period, while patients with diploid/near diploid profiles had low grade/stage tumors and survived. However, the multi-way analysis of variance performed in order to investigate the prognostic significance of ploidy pattern against tumor stage and grade showed a highly significant main effect of ploidy pattern. Moreover, the patients with hypodiploid DNA profile presented the worst prognosis. These results suggest that the DNA profile of PRCC is a highly significant prognostic index.

Aged↗

Morphological study of Trichophyton rubrum: ultrastructural findings after treatment with 4-amino-3-methyl-1-phenylpyrazolo-(3,4-c)isothiazole.

The antifungal activity of 4-amino-3-methyl-1-phenylpyrazolo-(3,4-c)isothiazole was studied on Trichophyton rubrum. The compound, at concentrations between 20 and 10 microg ml(-1), induces a remarkable reduction in the growth and causes deep morphogenetic anomalies. The ultrastructural modifications have demonstrated that the compound targets the cell membrane of the fungus, breaking down not only the endomembrane system, but also the 'outer' membrane, with consequent extrusion of materials in the medium. The results suggests a mechanism of action similar to other azoles clinically utilized.

Antifungal Agents↗

DNA ploidy pattern in choroidal melanoma: correlation with survival. A flow cytometry study on archival material.

BACKGROUND/AIMS: Paraffin embedded samples have provided an important source of material for retrospective cytofluorimetric studies, useful in establishing the predictive value of DNA content measurements. The aim of this study was to investigate the incidence and type of aneuploidy in choroidal malignant melanomas (CMM) and the significance in the clinical outcome (median follow up 55 months). METHODS: DNA content was quantified by flow cytometry in 61 CMM from archival material. Non-tumour ocular tissue was used as the reference diploid standard. Cases in which the coefficient of variation (CV) of the diploid peak was > 8% were excluded. The CMM were classified as spindle A, spindle B, mixed spindle and epithelioid, epithelioid, and necrotic. RESULTS: The frequency of the aneuploid DNA pattern was 38%. Necrotic tumours showed a worse clinical outcome independent of the ploidy pattern. Spindle A tumours were found to be diploid. Spindle B and mixed tumours showed a prevalent diploid and near diploid aneuploid pattern (DI < 1.3), yet aneuploidy was not correlated with a worse prognosis. The epithelioid tumours were prevalently diploid. However, 83% of the aneuploid tumours were hypodiploid (DI < 0.95), and showed the worst prognosis. CONCLUSION: These results indicate that increasing DNA abnormalities in CMM, especially in the epithelioid histotype, were associated with an increasing mortality.

Adult↗

Loss of phosphoserine polar group asymmetry and inhibition of cholesterol transport in Jurkat cells treated with cholesterylphosphoserine.

Cholesterylphosphoserine (CPHS) is a synthetic ester of cholesterol showing immunosuppressive activity. In the present study, we have used the T cell line Jurkat to investigate its mechanism of action. CPHS incorporates into cells reaching a molar ratio of 0.23 and 3.9 with the total phospholipid and cholesterol content, without inducing necrosis or apoptosis. CPHS incorporation elicits a dose-dependent binding of fluorescein isothiocyanate-labeled annexin V, suggesting that the steroid distributes in the external leaflet of plasma membrane exposing the phosphoserine group to the external cell environment and inserting the steroid ring into the phospholipid bilayer. In agreement with a preferential steroid association with sphingolipids, CPHS is included in a Triton X-100-insoluble complex when mixed with sphingomyelin and cholesterol. CPHS incorporation inhibits the esterification of low density lipoprotein (LDL)-derived cholesterol, producing a minor influence on the endogenous synthesis of cholesterol and on the acyl-CoA:cholesterol acyltransferase activity. In this effect, CPHS is as potent as progesterone (IC50 of 3.5 microM). It is concluded that the insertion of cholesterylphosphoserine (CPHS) in the Jurkat plasma membrane neutralizes the asymmetric distribution of the phosphoserine group and inhibits the movement of cholesterol to the endoplasmic reticulum. As CPHS is a negatively charged steroid, this last effect may be linked to the perturbation of sphingolipid/cholesterol-based microdomains, proposed to play a role in cholesterol trafficking.

Adjuvants, Immunologic↗

Quantitative ethnopharmacological study of the Campidano Valley and Urzulei district, Sardinia, Italy.

A new method has been developed for quantitative, phytotherapeutical analysis with a goal to create a general tool suitable for a wide range of research situations. This tool would allow one to gather data in such a format as to facilitate comparison with studies from other areas. The method was applied to data gathered from two sites in Sardinia, Italy (Campidano and Urzulei). Analysis was performed on 2635 responses (a) by plant, (b) by plant part, (c) by medicinal preparation and (d) by therapeutic use. This yielded specificity indexes which proved useful in comparing phytotherapeutic applications in the two geographic areas under study. In Urzulei the original phytotherapeutic heritage is deeply rooted in the local socio-economic history and clearly reflects the area's geographic isolation. Indeed, in this area, there is little reliance on modern health care. On the other hand, in Campidano, the body of phytotherapeutic application is more extensive. Indeed, due to migration-and to a lesser extent isolation- the latter area has been more affected by technological interference and cultural overlapping. In this area attention is widely focused on such modern ailments as glycemia, hypertension and constipation.

Italy↗

[Qualitative and quantitative parameters for prognosis in renal carcinoma in early and advanced stages].

AIM OF THE STUDY: A minority of stage I renal cell cancers have a bad prognosis, a minority of those in stage II-IV may behave favorably. Are there parameters which characterize such cases? In this study, a number of qualitative and quantitative parameters are used to detect differences between cases with at least 9 years of survival and those with a survival of less than 9 years. MATERIAL AND METHODS: 133 cases of renal cell cancer were subdivided into stage subgroups: Robson's I; Robson's II-IV. The following data and parameters were registered and/or measured: sex, stage, tumor size, histological type, mean nuclear profile area (mA) and pleomorphism (standard deviation of mean nuclear profile area--SDA) nuclear grade (NG) and combined nuclear grade (CNG), DNA index, cell proliferation, as determined by mitotic index (MI), per cent of PCNA positive cells (PCNA + cells %), per cent of S-phase cells (SP cells %), p53 and EGFR expression, intratumoral T lymphocytes. RESULTS: Older patients have a worse prognosis independently of the stage. Stage is the most discriminant qualitative parameter; tumor dimensions and both nuclear and combined nuclear grade are important too. Mean nuclear profile area and pleomorphism are also discriminant, while no prognostic value of histological type is shown and histology is not related to other parameters. Higher DNA index characterizes cases with worse prognosis, as well as MI, SP cells %, PCNA + cells %, and EGFR expression. No significant differences are detected for p53 expression and lymphoid infiltrates. A minority of patients with stage I tumors die within 9 years of diagnosis. They are older than survivors with the same stage, their tumors have larger nuclear area and greater pleomorphism, and are more frequently aneuploid with higher DNA index. A minority of patients with stage II-IV tumors survive at least 9 years from the time of diagnosis. They are younger than non-survivors in the same stages and have lower MI and PCNA positivity in the tumors, while other parameters are not discriminant.

Antigens, Neoplasm↗

Localization of a gene responsible for autosomal recessive demyelinating neuropathy with focally folded myelin sheaths to chromosome 11q23 by homozygosity mapping and haplotype sharing.

Hereditary motor and sensory neuropathy (HMSN) with focally folded myelin sheaths, or Charcot-Marie-Tooth type 4B (CMT4B), is a distinct clinical entity belonging to the heterogeneous group of autosomal recessive demyelinating neuropathies. We first described a large pedigree with CMT4B, which showed a high consanguinity level and an autosomal recessive pattern of inheritance. Through conventional linkage analysis, we excluded linkage of the locus segregating in this pedigree to any of the known genes responsible for other HMSNs. Using homozygosity mapping and haplotype sharing analysis, we were able to localize the disease gene in a 4 cM interval on chromosome 11q23, between the D11S1332 and D11S917 loci. On the basis of the clinical characteristics of the disease, we propose that this locus corresponds to the CMT4B gene.

Charcot-Marie-Tooth Disease↗

Usefulness of transthoracic and transoesophageal echocardiography in recognition and management of cardiovascular injuries after blunt chest trauma.

OBJECTIVE: To assess the diagnostic potential of transthoracic and transoesophageal echocardiography for the detection of traumatic cardiovascular injuries in patients suffering from severe blunt chest trauma. DESIGN: Prospective study over a three year period. SETTING: A regional cardiothoracic centre. PATIENTS: 134 consecutive patients (94 M/40 F; mean age 38 (SD 14) years) suffering from severe blunt chest trauma (injury severity score 33.5 (18.2)). Most patients (89%) were victims of motor vehicle accidents. EVALUATION: All patients underwent transthoracic and transoesophageal echocardiography within 8 h of admission. Aortography was performed in the first 20 patients and in a further five equivocal cases. RESULTS: Transthoracic echocardiography provided suboptimal images in 83 patients, detecting three aortic ruptures, 28 pericardial effusions (one cardiac tamponade), 35 left pleural effusions, and 15 myocardial contusions. Transoesophageal echocardiography was feasible in 131 patients and detected 14 aortic ruptures (13 at the isthmus), 40 pericardial effusions, 51 left pleural effusions, 34 periaortic haematomas, 45 myocardial contusions, right atrial laceration in one patient with cardiac tamponade, one tricuspid valve rupture, and one severe mitral regurgitation caused by annular disruption. For the detection of aortic rupture transoesophageal echocardiography showed 93% sensitivity, 98% specificity, and 98% accuracy. Time to surgery was significantly shorter (30 (12) v 71 (21) min; P < 0.05) for patients operated on only on the basis of transoesophageal echocardiographic findings. CONCLUSIONS: Transthoracic echocardiography has low diagnostic yield in severe blunt chest trauma, while transoesophageal echocardiography provides accurate diagnosis in a short time at the bedside, is inexpensive, minimally invasive, and does not interfere with other diagnostic or therapeutic procedures.

Accidents, Traffic↗

Atypical electromechanical dissociation in a patient with recurrent pulmonary embolism.

A 47-year-old man experienced recurrent pulmonary embolism resistant to aggressive medical and surgical prophylaxis. Although paraneoplastic hypercoagulability was suspected, no endoscopic or radiologic signs of malignancy were detected. Death was the result of electromechanical dissociation, which was attributed to right ventricular outflow obstruction. At autopsy, anaplastic lung carcinoma was found in the left basal segment with superimposed pulmonary infarction. A huge pedunculated thrombus was attached to the left ventricular apex and extended into the ascending aorta, obstructing the left ventricular outflow. To our knowledge, this is the first case of electromechanical dissociation due to left ventricular thrombus in a patient with pulmonary embolism. Radiologic and echocardiographic evaluation of such patients should take into account possible masking of the underlying neoplasm by embolic or hemorrhagic phenomena, or both, and the presence of left-sided cardiac thombi, which may cause catastrophic events.

Arrhythmias, Cardiac↗

Antifungal screening of seven new azole derivatives.

Two strains of the dermatophyte Epidermophyton floccosum were treated with seven new synthetic azole derivatives to determine their possible antifungal activity. Among these, two diazopyrazoles (1-phenyl-3-methyl-4-diazo-5-methanesulphonamid and 1,3-dimethyl-4-diazo-5-methanesulphonamid) and the triazole (4-methyl-6-t-butylpyrazolo[3,4-d] [1,2,3]triazole) were inactive at the highest dose tested (100 micrograms/ml). The 4-methyl-6-phenyl-pyrazolo[3,4-d] [1,2,3]triazole produced only a partial inhibition of growth, whereas the most active compounds were the two thiadiazines (6H-3-phenyl-5-methyl-7-(3,4-dichlorophenyl)pyrazolo[3,4-c] [1,2,5]thiadiazine-2,2-dioxide and 7-methyl-2-phenyl-4H-pyrazolo[1,5-c] [1,3,5]thiadiazine-4-one), and an aminoisoxazole (3-methyl-5-aminoisoxazole-4-thiocyanate), which induced a remarkable and sometimes complete reduction in the growth rate of the fungus. The structure-activity relationships are discussed.

Antifungal Agents↗

Inhibition by cholesterylphosphorylserine of T-cell-mediated immune responses in mice.

The synthetic analogue of phosphatidylserine, cholesterylphosphorylserine (CPHS) inhibits T-cell-mediated immune responses in mice. Tested in cultured mouse spleen cells, CPHS inhibits concanavalin A-induced activation of DNA synthesis (IC50, 3.5 microM). Injected i.p. during the efferent phase, CPHS (25-100 mg/kg) inhibits the manifestations of delayed-type of hypersensitivity. The compound (25 mg/kg i.p., daily) reduces the acute graft-versus-host reaction when given for 5 days to donor mice before the isolation of spleen cells used for the inoculum. These data suggest that the addition of a phosphorylserine group to a steroid ring may produce immunoregulatory compounds.

Adjuvants, Immunologic↗

Echocardiography in infective endocarditis: reassessment of the diagnostic criteria of vegetation as evaluated from the precordial and transesophageal approach.

The echocardiographic characteristics of vegetation used by precordial echocardiography (PE) have been transferred unchanged to transesophageal echocardiography (TEE), which has different image definition and structural resolution. Twelve diagnostic criteria of vegetation were tested for their accuracy in 52 patients evaluated by PE and TEE for suspected endocarditis (36 men, 16 women; mean age, 62 +/- 18 years; 42 with proven endocarditis). Results of PE and TEE were validated against gross anatomic and histologic findings. Significant differences (P < .05) included the fact that TEE disclosed more vegetations not prolapsing in the subvalvular region and in absence of valvular regurgitation. At TEE vegetations presented motion distinct from the endocardial surface, irregular conformation, and uneven margins. Only chaotic motion was significantly associated with vegetations at PE; size < 0.5 cm and increased echogenicity characterized pseudovegetations at PE. Other features such as shaggy echoes or location out of the annular zone (previously indicated as typical of vegetations) were not significantly associated with infective lesions. Discriminant analysis of TEE characteristics of vegetations disclosed that chaotic motion was the variable most significantly (P = .008) associated with vegetation. Coexistence of this sign with size < 0.5 cm and uneven margins was associated with 93.3% sensitivity and 83.7% specificity. In conclusion, the echocardiographic aspect of vegetations is rather different when examined from the precordial and the transesophageal approach. Learning about pitfalls and normal variants should improve TEE specificity in the assessment of infective lesions.

Aged↗

Comparative diagnostic value of transesophageal echocardiography and retrograde aortography in the evaluation of thoracic aortic dissection.

The aim of this study was to assess the comparative diagnostic value of transesophageal echocardiography (TEE) and retrograde aortography for morphologic evaluation and anatomic mapping of aortic dissection. Seventy patients (aged 18 to 79 years) were prospectively evaluated with both techniques for suspected aortic dissection. In 64 patients, findings on aortography and TEE could be validated against intraoperative (n = 53) and postmortem (n = 11) findings. Examination time was significantly shorter for TEE (9 +/- 6 vs 48 +/- 25 minutes; p < 0.001). For the detection of aortic dissection, aortography showed lower sensitivity (87.5% vs 97.5%) and negative predictive value (85.3% vs 96.7%; both trends did not reach statistical significance) due mostly to the inability to identify noncommunicating dissection (dissection without intimal tears). For the epiphenomena of aortic dissection, aortography was significantly more accurate (97.2% vs 78%; p < 0.05) in assessing the site of entry, and TEE was more accurate in identifying thrombus formation (90% vs 65%; p < 0.05). There was no significant difference between aortography and TEE with regard to assessing secondary tears, aortic regurgitation, coronary dissection, and extension of the dissection. Thus, both TEE and aortography offer detailed anatomic mapping for guided surgical interventions. In elective patients, integration of both techniques seems the best approach; in unstable patients, TEE may be preferential because it is less invasive, requires no contrast injection, and provides accurate diagnosis in a short time at the bedside.

Adult↗

Ploidy pattern and cell cycle in breast cancer as detected by image analysis and flow cytometry.

Both image analysis (IA) and flow cytometry (FCM) may be applied to detect ploidy pattern and cell cycle fractions. However, they have different performance characteristics and may yield different results. The two approaches are applied in this study to 66 breast cancers: IA on imprints and FCM on fresh tissue. The percent coefficient of variation (CV) ranged from 2.0 to 7.0 (mean 5.5; SD 1.1) in IA and from 2.0 to 7.0 (mean 4.4; SD 1.1) in FCM. The values were well correlated. With regard to ploidy pattern, the agreement between the two methods was 92.4%; disagreements were due to four cases being aneuploid by IA but not detected by FCM and one case being aneuploid by IA but tetraploid by FCM. This suggests that IA is capable of detecting aneuploidy with more sensitivity than FCM. In diploid cases, the percent values of cells in G0/G1, S-phase (SPF), and G2M phase were concordant and well correlated. In aneuploid cases, IA was more sensitive than FCM in detecting aneuploid fraction as well as G2M phase, whereas FCM was more sensitive than IA in detecting SPF. A good correlation was found between the DNA indexes (DIs) obtained with the two methods.

Aneuploidy↗

Absence of APP713 mutation in Italian and Russian families with schizophrenia.

A recent study has shown a mutation at codon 713 of the amyloid precursor protein (APP) gene in a schizophrenic patient. We have analyzed the MaeIII restriction site caused by that mutation in Italian and Russian families with schizophrenia. No mutations were observed suggesting that the APP713 mutation is unlikely to be linked to the pathogenesis of such a psychiatric disorder.

Alzheimer Disease↗