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Biomedical subjects

S Costa

Publications and source records attributed to S Costa.

At least 109 records · Page 6Linked to original sources

[Emergency ultrasonography].

We reviewed the emergency US exams carried out in the Radiology Department of the Sesto S. Giovanni Hospital on patients referred from the First Aid, Surgery and Medicine Depts in 1994. 202 of 8,400 US exams (2.7%) were emergencies in patients of both sexes aged 15 to 83 years. The exams were carried out in the daytime by 4 radiologists with different (longer/shorter) experience. The results were arranged in tables showing the referring department, the number of exams according to the anatomical district, the number of negative exams (122 cases) and of the exams where the clinical suspicion was confirmed (80 cases), as well as the frequency of the different conditions diagnosed. The conditions usually involved the abdominal organs and particularly the bile ducts (48 cases), showing gallstones which were quickly operated on. Renal colics were the second most frequent finding (10 cases). The results of many precautionary exams were poorly significant. Considering the numerous indications of emergency US, currently including also acute appendicitis and soft periskeletal tissue traumas, we conclude that more operators and technically adequate equipment are needed.

Adolescent↗

Adenovirus 5 E1A induced differentiation of P19 embryonal carcinoma cells requires binding to p300.

We transfected P19 embryonal carcinoma (EC) cells with genes encoding the adenovirus 5 E1A products. Expression of either the 12S or 13S transcripts yielded P19 cells either incapable of proliferating or able to proliferate but having lost the characteristics of the EC cell parent. The proliferating clones of E1A expressing P19 cells were incapable of differentiating in response to retinoic acid or dimethyl sulfoxide, no longer expressed the SSEA-1 surface antigen characteristic of EC cells, and did express cytokeratin 55, a marker of epithelial tissues. We used a number of 12S E1A constructs carrying deletions in the first exon and found that the effects on P19 cell growth and differentiated properties were lost with alterations affecting either the N terminal 25 amino acids or the CR1 region of the E1A protein. Both regions are required to bind the cellular p300 protein that we showed is present in P19 cells. We conclude that binding of E1A to the p300 protein in P19 cells results in the loss of EC cell characteristics.

Adenovirus E1A Proteins↗

Presurgical assessment and therapy of microinvasive carcinoma of the cervix.

Retrievable pathological specimens and clinical data on 70 patients with microinvasive carcinoma diagnosed on surgical specimens from cone biopsy or hysterectomy (Stage IA) were reviewed and compared to pertinent findings in the literature with the intent of evaluating diagnostic criteria and defining pathological features that may influence the outcome by therapy. Emphasis was given to the preoperative assessment emphasizing that both an accurate colposcopic evaluation and a detailed pathological analysis may reliably point to a conservative therapeutic approach. Increasing depth of stromal invasion was associated with lesion width as well as with endocervical extension, as measured on colposcopy, microcolpohisteroscopy, and histology. Lymph-vascular space involvement was significantly related to depth of invasion. Two patients of 28 with dissected nodes had node metastases as well as lymph-vascular space involvement. Both developed a pelvic recurrence. One had a > 1- to < or = 3-mm invasion depth, the other a > 3- to < or = 5-mm lesion invasion. While advocating a conservative procedure for Stage IA1, we suggest discrimination with regard to Stage IA2 because we believe that lymph-vascular involvement should be meticulously evaluated. In fact, > 1- to < or = 3-mm lesions without lymph-vascular space involvement can be conservatively treated, while for any other lesion falling within the Stage IA2 category a modified radical histerectomy plus pelvic lymphadenectomy should be recommended.

Adult↗

A sensitive and reliable method for assaying true human insulin without interaction with human proinsulin-like molecules.

In the present study our interests focused on the evaluation of a high capacity assay (MEIA) which allows true insulin determinations in the absence of cross-reactivity with proinsulin-like molecules. This method was compared to a commercially available radioimmunoassay (RIA) for insulin determination. As the latter gives insulin levels which represent a mixture of insulin and proinsulin-like molecules, the proinsulin-like molecules were quantitated by subtracting the true insulin levels measured using MEIA from the total insulin levels obtained using RIA. These methods were applied for the analysis of blood samples drawn in 63 normal subjects, 16 obese subjects, 3 patients submitted to islet transplantation and 4 patients with insulinoma. The MEIA was precise, fully automated and time-saving, making its application on a routine basis particularly attractive. MEIA and RIA were equally able to correctly quantify human insulin molecules. On the contrary, the antibody present in the true insulin assay did not interact with proinsulin-like molecules, which were recognized even in the presence of increasing insulin levels. In normal subjects, the true and total insulin levels in the fasting state and at the time peak after glucose- or arginine-induced endogenous insulin release were well correlated at r = 0.88 and 0.89, respectively. Interestingly, total insulin values were overestimated by 10%-16% as compared with true insulin levels, which represent proinsulin values superimposable on previously reported data. Proinsulin-like molecules made up 50% of the total insulin in obese and transplanted patients, and about 70% in patients with insulinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of an acute increase in plasma triglyceride levels on glucose metabolism in man.

The aim of the study was to evaluate the effects of an acute increase in triglyceride levels induced by Intralipid (Kabivitrum, Stockholm, Sweden) infusion on forearm glucose uptake, glucose oxidative metabolism, and hepatic glucose production independent of circulating free fatty acid (FFA) levels in man. Six normal subjects underwent three different tests in random order. Each test consisted of a control period of 120 minutes followed by a euglycemic, hyperinsulinemic clamp lasting 120 minutes. In test 1, a high-dose intravenous Intralipid infusion was performed to increase triglyceride and FFA levels. In test 2, heparin (30 U/min) plus low-dose Intralipid infusions were performed to maintain triglyceride at normal levels and increase only FFA levels. Test 3 was performed as a control study. During the 120-minute control period, forearm glucose uptake and hepatic glucose production were not affected by increasing only FFA levels (test 2) or FFA and triglyceride levels (test 1) as compared with the control study. On the contrary, glucose oxidation was significantly decreased as compared with the control study during tests 1 and 2, without a further significant decrease during simultaneously increased FFA and triglyceride levels. Concomitantly, lipid oxidation was similar in tests 1 and 2, at values significantly greater than in test 3. During the euglycemic clamp, forearm glucose uptake and glucose oxidation were significantly lower during tests 1 and 2 than test 3. At variance with the control period, the increase of triglyceride levels during test 1 caused a significant 30% to 40% decrease of both parameters as compared with test 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Beta-interferon treatment of cervical intraepithelial neoplasia: a multicenter clinical trial.

Forty-nine women with cervical intraepithelial neoplasia (CIN) grade II were treated with systemic and/or local beta-interferon (beta-IFN) applications. The aim of the study was to compare the efficacy of different routes for the administration of beta-IFN, evaluate local and systemic beta-IFN tolerance, and determine whether disappearance of neoplastic lesions was related to the resolution of the concomitant human papillomavirus infection. The patients were randomized to receive intramuscular, intralesional or a combination of intramuscular and intralesional administration, or conventional treatment. Significant differences in the rate of lesion regression were observed between treated and untreated women. The highest frequency of complete response was observed with the therapy combining intramuscular and intralesional treatment.

Adult↗

The continuous low dose insulin and glucose infusion test: a simplified and accurate method for the evaluation of insulin sensitivity and insulin secretion in population studies.

In this study we investigated a simple nonlabor-intensive method to evaluate insulin sensitivity and beta-cell function which is suitable for application in population studies. The method is a refinement of the modified Harano test and consists of a continuous low dose insulin (25 mU/kg.h) and glucose (4 mg/kg.min) infusion test (LDIGIT) lasting 150 min. Insulin sensitivity was evaluated as the MCR of glucose divided by the steady state serum insulin level achieved at the end of the test. Insulin secretion was expressed as the incremental area for C-peptide concentration during the first 15 min of the test. We compared the indices of insulin sensitivity and insulin secretion yielded by LDIGIT with those derived from the euglycemic clamp and the hyperglycemic clamp, respectively. Fifty-four subjects underwent a LDIGIT (33 with normal glucose tolerance and 21 with impaired glucose tolerance); of the 54, 19 were submitted to a euglycemic clamp, 18 to a hyperglycemic clamp, and 10 to a modified Harano test (insulin infusion, 50 mU/kg.h; glucose infusion, 6 mg/kg.min). LDIGIT overcame the drawbacks associated with the modified Harano test because it resulted in more stable final glucose levels and prevented the occurrence of hypoglycemic episodes. No significant differences were found between the insulin sensitivity index (ISI) of the LDIGIT and that of the euglycemic clamp for each group of subjects. Moreover, there was a strong correlation between the ISI determined by LDIGIT and the ISI determined by clamp (r = 0.90; P < 0.0001), and the best regression line was not different from the identity line, suggesting that the two indices are equivalent. The index of insulin secretion provided by LDIGIT correlated well with that of the hyperglycemic clamp (r = 0.82; P < 0.001) and was significantly higher in overweight subjects than in normal weight subjects. In conclusion, LDIGIT is a simple and accurate method to assess insulin sensitivity and secretion. It can be useful in population studies and in situations when more complex techniques are not feasible.

Adult↗

Human papillomavirus infections in vulvar precancerous lesions and cancer.

To elucidate some of the recently arisen issues related to the bimodal disease pattern of vulvar intraepithelial lesions (VIN) and vulvar cancer, a series of 27 consecutive women with vulvar symptoms was analyzed for human papillomavirus (HPV) involvement by colposcopy, light microscopy and in situ hybridization (ISH) for HPV types 6, 11, 16, 18, 31, 33 and 42. Altogether, HPV DNA was discovered in 13/27 (48.1%) of the lesions by ISH; the rest were HPV DNA negative for the seven HPV types tested. HPV DNA was present in both of two exophytic lesions (HPV 6 in condyloma and HPV 16 in verrucous cancer). Of the flat lesions, 7/13 (53.8%) were HPV DNA positive. HPV 6 was confined to low grade lesions (HPV/non-VIN and VIN 1), whereas HPV 11 was found in a case of VIN 3 as well. Of the invasive carcinomas, three of four were HPV DNA positive (2 HPV 16 and 1 HPV 31). Dystrophic changes were detected in three of four invasive carcinomas and in all three HPV 16-positive lesions. Dystrophic changes were absent in 9 of 14 (64.3%) of HPV DNA-negative lesions. Fifty percent (7/14) of vulvar warty lesions (without concomitant VIN) were found in women younger than 60. Three of four invasive carcinomas occurred in women older than 60. This small series provided additional evidence of HPV involvement in the pathogenesis of VIN lesions, and the findings support the hypothesis of a multifactorial etiology in vulvar carcinogenesis in which HPV, dystrophic changes and chronic inflammatory disease play a synergistic role.

Adult↗

Expression of CD44 splice variants in normal, dysplastic, and neoplastic cervical epithelium.

Expression of splice variants of the CD44 adhesion molecule has been implicated in metastatic spread of various human tumor cells, including malignant lymphomas and colon, mammary, and gastric carcinomas, and has been correlated to a poor prognosis for the respective patients. To determine whether variant CD44 molecules might also contribute to the metastatic spread of cervical cancer, we analyzed the CD44 expression pattern in normal cervical epithelium and in low- and high-grade cervical dysplasia and compared it with invasive and metastasizing cervical cancers, including cell lines derived thereof by immunofluorescence and exon-specific PCR amplification of reverse-transcribed CD44 transcripts. We observed that normal cervical epithelium and dysplastic lesions express high levels of standard CD44 in the basal and spinous epithelial layers. CD44 molecules encompassing variant exons v5 and v6 are strongly expressed throughout the epithelium. Low levels of variants encompassing exon v7 are expressed in basal and spinous layers, with particular strength in the suprabasal layer. Low levels of epitopes encoded by v8 and v10 are expressed in the basal and spinous layers. In cervical cancers, including lymph node metastasis, we observed strong expression of v5 and v6, but almost no expression of v7, v8, and v10. Expression of the CD44 standard form appeared to be down-regulated in some cancers when compared to normal cervical epithelium. Thus, expression of variant CD44 molecules is related to distinct differentiation of mucosal squamous epithelia in the female genital tract. No correlation of the expression of variant CD44 isoforms, including the v7-v8 fusion epitope with tumor progression or lymphatic spread, was observed.

Alternative Splicing↗

Impact of sexual habits on the clinical evaluation of male HPV infection.

A series of 199 male regular sexual partners of women attending an STD clinic for the examination and treatment of HPV-associated diseases was examined by peniscopy, surgical biopsy and nucleic acid hybridization for the presence of clinical, histological and molecular markers pathognomic of HPV infection. There was a 100% correlation between condylomata acuminata and detection of HPV type 6 or 11 DNA. Papillary lesions displayed neither histological signs of HPV infection, nor did they harbor HPV DNA (viral types 6, 11, 16, 18, 33) while 44.9% (22/49) of acetowhite epithelia showed HPV-suggestive histological changes. Of the 19 analysed for HPV DNA, 15.8% (3/19) harbored HPV 6/11 and 16 DNA. Regular male and female sexual partners did not always harbor the same HPV types, showing that latent or occult infection and the sexual habits of each individual play an important role in the clinical manifestations of HPV infection observed in sexual couples. The present data show that: i) the likelihood of developing a clinical HPV lesion was affected, to a large extent, by the previous sexual history and habits in the partners of women with flat condylomata, while partners of women with condylomata acuminata or CINs displayed a higher correlation with the current state of infection in their regular partner; ii) despite the assessed infective state of their consorts, men with a low lifetime number of sexual partners seldom displayed HPV-associated acetowhitening.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

A program to measure new energetic particle nuclear interaction cross sections.

The Transport Collaboration, consisting of researchers from institutions in France, Germany, Italy and the USA, has established a program to make new measurements of nuclear interaction cross sections for heavy projectiles (Z > or = 2) in targets of liquid H2, He and heavier materials. Such cross sections directly affect calculations of galactic and solar cosmic ray transport through matter and are needed for accurate radiation hazard assessment. To date, the collaboration has obtained data using the LBL Bevalac HISS facility with 20 projectiles from 4He to 58Ni in the energy range 393-910 MeV/nucleon. Preliminary results from the analysis of these data are presented here and compared to other measurements and to cross section prediction formulae.

Cosmic Radiation↗

On the mechanisms of genotoxicity and metabolism of quercetin.

Quercetin has been the subject of numerous studies on its genetic toxicity and carcinogenicity. Despite its well-proven genetic damaging activity for various genetic end-points (reverse mutations, induction of SOS functions, induction of sister chromatid exchanges, chromosomal aberrations and micronuclei), the mechanisms of genetic damage by quercetin remain, by and large, unknown. The present study aims to further extend the observations on the possible active oxygen species mediated DNA-damaging activity of quercetin and the role of cytochrome P450-dependent metabolism on the genotoxicity of quercetin. The results reported in this work show that quercetin can produce the OH. radical, as assessed by deoxyribose degradation in the presence of Fe3+/EDTA (ethylenediaminetetraacetic acid), and that it induces strand breakage in isolated plasmidic DNA (pUC18). The data support the hypothesis that the production of OH. is mediated by H2O2. The results with genetically engineered V79 cells expressing rat cytochromes 1A1, 1A2 and 2B1 failed to demonstrate metabolism of quercetin, as indicated by the fact that neither an enhancement nor a decrease in the genotoxicity of quercetin was observed. Results obtained on the pH dependence of the induction of chromosomal aberrations by quercetin in V79 cells show that, as the pH value of the medium is increased to 8.0, there is a significant increase in the number of aberrant cells, as expected if oxygen radicals are responsible for the formation of chromosomal aberrations.

Animals↗