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Biomedical subjects

D Gandini

Publications and source records attributed to D Gandini.

At least 37 records · Page 2Linked to original sources

Novel small deletions of the p53 gene in late-stage B-cell chronic lymphocytic leukaemia.

A group of 20 CLL patients selected for advanced clinical stage p53 mutations were analysed by single-strand conformational polymorphism (SSCP) following PCR amplification of exons 5-9. In two patients abnormal SSCP of either exon 5 or exon 8 was found and PCR products were analysed by direct sequencing. A hemizygous or homozygous 12bp deletion at codon 135 and 3bp heterozygous deletion at codon 264 were detected; also, in the latter sample a heterozygous mutation at codon 282 (Arg to Gln) was found. To our knowledge, this is the first report of p53 deletions in B-CLL. The two patients were elderly, and both had a rapidly progressive disease in the absence of unfavourable cytogenic abnormalities. These findings support a role for p53 alterations in the clinical course of some B-CLL patients.

Aged↗

Screening for breast cancer: report of a population-based experience in the city of Milan, Italy.

AIMS AND BACKGROUND: Mammographic screening is recommended as a current health practice. The aim of the present study is to report the results of a new program which started in the city of Milan in 1989. METHODS: A total of 4882 women aged 50 to 61 years and resident in quarter no. 16 of Milan were invited by mail to attend the screening at the San Paolo Hospital based on two-view mammography and physical examination. RESULTS: A total of 2953 (60.5%) women attended the first screening round, and 18 cancers were detected (1 Tis, 8 T1, 9 T2). The detection rate was 6.9 x 1000, and the prevalence/incidence ratio was around 3.5. CONCLUSIONS: The study confirms the feasibility of breast cancer screening in an urban setting by using the existing general hospital facilities and should be considered as a possible model for other urban experiences.

Aged↗

Retinoic acid-induced decrease of DNA synthesis and peroxidase mRNA levels in human thyroid cells expressing retinoic acid receptor alpha mRNA.

In order to clarify the effect of retinoids on thyroid cell growth and function, the presence of retinoic acid receptors (RARs) and the action of retinoic acid (RA) on DNA synthesis and on thyroid peroxidase (TPO) and thyroglobulin (TGB) mRNA expression were investigated in primary cultures of human thyroid follicular cells. A time and dose-dependent reduction in 3H-thymidine (3H-thy) incorporation was found in cells exposed for 48 h to all-trans-RA up to 1 microM. A cytotoxic effect was found only with the higher dose of 50 microM. The RA-induced decrease of 3H-thy incorporation was reflected by parallel change in DNA content of cell monolayers. The inhibitory effect of 1 microM RA on 3H-thy incorporation ranged from 28.5 +/- 4.6% in normal cells to 42 +/- 3.2% in adenomatous cells. In addition, 1 microM RA significantly reduced basal and TSH-induced TPO mRNA levels in normal, goitrous and adenomatous cells, but did not alter TGB mRNA levels. Furthermore, in these cells the study of RAR alpha and beta mRNA showed the presence of two major RAR alpha mRNA transcripts of approximately 3.5 and 2.8 Kb in size, whereas RAR beta mRNA was undetectable. Overall, our data indicate that RAR alpha gene is expressed in human thyrocytes and that RA may be involved in the regulation of the human thyroid by reducing proliferation and function of follicular cells.

Adenoma↗

Expression of p53 gene in B-CLL peripheral lymphocytes.

The p53 tumor suppressor gene expression has been studied in 23 B-CLL cases at different clinical stages. The analysis failed to show a direct correlation with each stage, but the significantly lower frequency of a BglII RFLP in the pathologic population suggests a role of this gene in B-CLL. Northern Blot analysis showed the expression of p53 mRNA in all the B-CLL cases. A protocol for the RT-PCR methods was set up to study a very small amount of materials which should be better used for sequence analysis.

DNA, Neoplasm↗

Immunogenotypic characteristics of chronic lymphocytic leukemia patients from northern Italy.

Ig gene analysis, carried out in 25 patients failed to show rearrangement patterns typical of each stage, but, nevertheless, confirmed the monoclonal origin of leukemic cells in these patients. In addition, in 14 of them the pattern of Ig gene rearrangements measured on two different occasions was analyzed. Only in patients who had received chemotherapy, the intensity of the Ig germline band was greater than that of the rearranged bands, indicating the reduction of lymphocytosis after the therapy. Thus, though Ig gene rearrangement could not distinguish the CLL stage, our data confirm the usefulness, at all clinical stages, of Ig gene analysis as a tool in the evaluation of the efficiency of the therapy.

Antibodies, Monoclonal↗

Simplified construction and characterization of yeast artificial chromosome libraries.

Three yeast artificial chromosome (YAC) libraries were constructed using two human cell lines and the pYAC-RC vector. The main differences from the previously described methods were: i) genomic DNA was digested in low melting point (LMP) agarose blocks with the rare cutting enzyme ClaI; ii) DNA was ligated in melted LMP agarose after agarase treatment; iii) spheroplast regeneration plating was done in calcium alginate thin layer. In addition, a panel of PCR primers was used to identify quickly the presence in the libraries of repetitive and single copy human DNA sequences.

Base Sequence↗

[Cytofluorometric study of myeloperoxidase (MPO) expression in neutrophilic granulocytes of subjects with primary or secondary MPO deficiency: analysis of the histographic antigen distribution using the Kolmogorov-Smirnov mathematical model].

Neutrophil granulocytes from 12 subjects with primitive myeloperoxidase (MPO) deficiency (6 totally deficient) and 16 patients with secondary partial MPO deficiency were tested using two different anti-MPO monoclonal antibodies (MoAbs), in combination with a flow cytometer. Results demonstrated three different patterns of immunoreactivity with the MPO protein:i) a bright MPO antigenic expression, typical of patients with secondary MPO deficiency (comparable with that observed in the control group); ii) a medium MPO antigenic expression, typical of subjects with hereditary partial MPO deficiency; and iii) a dim MPO antigenic expression, characteristic of individuals with hereditary total MPO deficiency. No significant differences in granulocyte MPO reactivity were demonstrated for the two MoAbs. Furthermore, in two individuals with complete primitive deficiency, the single histogram analysis of MPO fluorescence seemed to show that only 38% (case 1) and 44% (case 2) of neutrophil were reactive with the MoAbs anti-MPO: the use of multiple histogram analysis in combination with Kolmogorov-Smirnov statistics allowed us to demonstrate that all the cells express a low density of MPO antigen. These data suggest that patients with primary MPO deficiency have different amount of MPO antigens in the neutrophils, and the levels of MPO fluorescence seem to decline concurrently with enzyme activity, thereby suggesting the presence of a diminished MPO production. On the contrary, in most cases of acquired MPO deficit, the reduced cytochemical activity contrasts with normal antigenic reactivity: this might be the result of the presence of an inactive enzyme.

Antibodies, Monoclonal↗

Digital subtraction angiography of the kidney.

Intravenous and intra-arterial digital subtraction angiography (DSA) was performed in 88 patients: 34 with tumours, 10 with renal trauma, 26 with suspected renovascular hypertension, 6 with vascular impression on the renal pelvis, 8 with nephrolithiasis and 4 with sonographically abnormal kidneys. Venous and arterial DSA always gave diagnostically useful images. Intravenous DSA is valuable in patients with suspected renovascular hypertension or after vascular surgery, percutaneous transluminal angioplasty and transcatheter embolisation. Arterial DSA is preferable to venous DSA in other clinical situations, particularly in the evaluation of renal tumours, and may be recommended in preference to conventional angiography.

Adult↗

Monoclonal origin of B cells producing k, lambda and k lambda immunoglobulin light chains in a patient with chronic lymphocytic leukemia.

Immunoglobulin gene rearrangements can be used as genetic markers of clonality in the study of B-cell populations [4]. We have therefore analysed the structure and expression of heavy and light chain immunoglobulin genes in lymphocytes of a patient with chronic lymphocytic leukemia, where we found both k and lambda producing B cells, but in most of the cells both k and lambda chains were co-expressed on the same surface membrane. Single rearrangements were observed in mu, JH, k and lambda DNA sequences, thus providing strong evidence for the monoclonal origin of the cells bearing different light chains. Moreover, the analysis of Ig sequence RNA showed, in addition to normal mu, k and lambda mRNA molecules, high levels of a small lambda related RNA sequence. These findings are discussed in relation to a model of B-lymphocyte differentiation which could be either an additional or an alternative hypothesis to the current one of isotypic exclusion.

Aged↗

[Bronchofibroscopic and bronchographic aspects of the senile bronchus].

A comparison is made between the bronchofibroscopic and bronchographic pictures observed in aged volunteers with healthy lungs and bronchi. The main finding was of simple atrophy of varying type and degree (more or less marked, diffuse or local), mainly affecting the large bronchi. Age and the extent and magnitude of the alterations were not related: marked atrophy was noted in presenile and slight atrophy in greatly aged subjects. Both types of atrophy may be treated as physiological, since they are presumably connected with differences in the incidence of various factors (diasthetic, constitutional, dysmetabolic, hormonal) and variously numerous microtrauma. The same picture was given by both types of examination, despite the wide differences between their methods.

Age Factors↗

The laryngeal mask airway: potential applications in neonatal health care.

The laryngeal mask airway is a completely new concept in airway management and has the potential to provide a third airway option for the neonate. The device sits in the hypopharynx at the interface between the gastrointestinal and respiratory tracts, where it forms a circumferential low-pressure seal around the glottis. This article provides an overview of the laryngeal mask airway and focuses on its potential as a neonatal airway outside the operating room.

Anesthesiology↗

Detection of melanoma cells in peripheral blood and sentinel lymph nodes by RT-PCR analysis: a comparative study with immunohistochemistry.

The presence of lymph node metastases is the best prognostic factor for predicting relapse or survival in melanoma patients. It has been demonstrated that melanoma metastases spread through the first lymph node(s) draining the tumor (sentinel lymph node, SN) to the lymphatic system and that detection of melanoma cells in peripheral blood directly correlates with prognosis in melanoma. To identify lymph node metastases and circulating melanocytes, we developed a single-step reverse transcriptase-polymerase chain reaction assay (RT-PCR) for detection of two melanoma-specific markers: the tyrosinase gene, which encodes an enzyme associated with melanin synthesis, and melanoma antigen-related T-cells, which are present in tumor infiltrating T-lymphocytes. This method detects two tumor cells in a background of 10(7) lymphocytes. Thirty patients with stage I-IV cutaneous melanoma entered the study. Blood samples were taken preoperatively, one month after excision of the primary melanoma lesion and the SN or total lymphadenectomy, and before the start of chemotherapy and every three months thereafter in metastatic patients. SNs were collected from 22 patients, bisected and analyzed by RT-PCR and routine pathological and immunohistochemical tests. The preliminary results indicate that RT-PCR for melanoma markers is a sensitive and valuable method for the detection of micrometastases and for early diagnosis and staging of melanoma.

Adult↗