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Biomedical subjects

A Castagnoli

Publications and source records attributed to A Castagnoli.

At least 19 recordsLinked to original sources

A new chromosomal breakpoint in Ph positive, bcr negative chronic myelogenous leukemia. Report of a case.

We report a new case of Ph positive chronic myeloid leukemia (CML) without the classical rearrangement in Mbcr. By Southern blot analysis the molecular breakpoint was mapped 3 to 8 kb upstream of Mbcr. This region has not been shown to be rearranged in any other described case of CML. We did not detect any specific abnormal BCR-ABL transcript even with the use of the very sensitive RNA-PCR technique.

Base Sequence

Suppression of tumorigenicity and anchorage-independent growth of BK virus-transformed mouse cells by human chromosome 11.

Viral transformation models may be useful for detecting and mapping human tumor suppressor genes. BK virus (BKV), a human papovavirus, readily transforms rodent cells but is unable to transform human cells, suggesting that oncosuppressive functions expressed in human cells control BKV oncogenic activity. We have transferred human chromosome 11 to BKV-transformed mouse cells. All of the cell clones were suppressed in the tumorigenic phenotype and anchorage-independent growth, except one clone which was nontumorigenic but maintained the ability to grow in soft agar. Cytogenetic analysis and DNA hybridization with chromosome 11-specific probes showed that all the reverted hybrids had an intact human chromosome 11, except the clone growing in semisolid medium which had lost the short arm. The results suggest that a gene located on 11p controls anchorage independence, whereas a gene on 11q controls the tumorigenicity of BKV-transformed cells. BKV T-antigen was expressed in all the hybrid clones at the same level as in the parental cell line, indicating that the putative human tumor suppressor gene(s) do not inhibit expression of the viral oncogene and must operate by another mechanism in inducing reversion of the oncogenic phenotype. Since BKV-transformed mouse cells are highly susceptible to retrovirus infection, this model can be used for searching and cloning tumor suppressor gene(s) by retrovirus-mediated "insertional mutagenesis".

Animals

Merkel cell carcinoma and iodine-131 metaiodobenzylguanidine scan.

Two cases of Merkel cell carcinoma, a neuroendocrine neoplasia of the skin, investigated with iodine-131 metaiodobenzylguanidine (131I-mIBG) scintigraphy, are reported. Uptake in the tumor was evident only in 1 case. The possible diagnostic and therapeutic role of 131I-mIBG in patients with this rare neoplasm is discussed.

3-Iodobenzylguanidine

Suppression of tumorigenesis by the breast cancer cell line MCF-7 following transfer of a normal human chromosome 11.

Breast cancer development is associated with several genetic abnormalities. Loss of heterozygosity in the short arm of chromosome 11 has been observed in 30% of tumors. We found homozygosity at five chromosome 11 polymorphic loci in genomic DNA of the MCF-7 breast carcinoma cell line, suggesting a possible loss of one chromosome 11. We have studied the transformed and tumorigenic phenotypes of MCF-7 cells following introduction of a normal human chromosome 11 via microcell fusion. MCF-7/H11 cell hybrids, containing chromosome 11, showed in vitro characteristics similar to the parental cell line. However, tumorigenicity in athymic mice was completely suppressed. Since tumor formation by MCF-7 cells is estrogen dependent, we have analysed the expression of the estrogen receptor and of the estrogen-activated gene pS2. No difference was detected between the parental MCF-7 cells and the derived chromosome 11 cell hybrids, indicating that the mechanism of MCF-7 tumor suppression by chromosome 11-associated functions does not directly involve the estrogen/estrogen receptor molecular pathway.

Animals

[The nimodipine therapy of acute focal cerebral ischemia (minor stroke). A clinical study with an assessment of regional cerebral blood flow by SPECT].

Aim of the study is the evaluation of therapeutic effectiveness of nimodipine in acute focal cerebral ischaemia. Thirty patients affected by minor ischaemic stroke divided in two randomized groups have been studied consecutively: all the patients were treated with standard therapy, nimodipine was delivered in addition only to the patients of the first group. Both clinical evaluation using Mathew scale, modified by Gelmers, and flowmetric evaluation with SPECT were performed at different times. The results haven't shown any significant statistical difference in the effectiveness of the therapy between the two groups even if a positive clinical trend was evidenced in the group treated with nimodipine. The flowmetric study has shown the poor homogeneity of the groups from a physiopathological point of view not-with-standing the two groups were similar for the clinical severity, sex, age and vascular risk factors. We conclude that is advisable to carry out further trials in which the comparison study groups are more numerous and balanced also from a physiopathological point of view.

Acute Disease

Prevalence of the archetypal regulatory region and sequence polymorphisms in nonpassaged BK virus variants.

Since the first isolation and characterization of BK virus (BKV), a number of BKV variants which differ in genomic structure or antigenic determinants have been described. The regulatory region, in particular, the enhancer elements, show the most divergent sequences among different isolates. The structural organization of a putative ancestral prototype or archetype, from which all of the variants are probably derived, has been proposed. By sequencing the regulatory regions of 13 different isolates from the urine of bone marrow transplant recipients, we determined the structures and sequences of BKV variants diffused in the human population. The enhancer region was amplified by polymerase chain reaction to avoid passage in culture, and the product was directly sequenced. The structure most frequently observed is in agreement with the postulated archetype, containing a single enhancer element with no repeats. By sequence analysis we identified four hot spots of nucleotide variation. These variations are consistent with the existence of two consensus sequences. One sequence motif, observed in about 85% of the isolates, is referred to as the archetypal BKV, while a second motif, observed in the remaining 15% of the variants, is highly reminiscent of the AS strain.

BK Virus

[Serum beta 2-microglobulin and HLA alloantigens in primary Gougerot-Sjögren syndrome. A possible relation with HLA-DR3 specificity].

The relationships between some allo-antigens of the HLA system and beta 2-microglobulin (beta 2m) serum level were examined in a group of 24 subjects with primitive Sjögren's syndrome (pSS). While the beta 2m serum level of all the patients with pSS were higher at the limits of significance (p congruent to 0.05), compared to the values of the 14 control subjects, the division of the patients into two sub-groups of 14 and 10 subjects, according to the presence or absence of the haplotypes DR2 and/or DR3, pointed up a beta 2m serum level which was significantly higher in the first compared to the second (p less than 0.02) and to the group of normal subjects (p less than 0.01). Among the individual haplotypes studied, only the DR3 was observed with a significantly greater frequency (p less than 0.01) in the patients compared to the control group. The haplotype DR3 and also the B8, although at a lesser level, were found to be correlated with a high value of the serum beta 2m: p less than 0.004 and p less than 0.05 respectively. A similar association was not found for the DR2 and DRW52 specificities.

Adult

Direct detection of a missense mutation causing severe hemophilia A by PCR amplification and fluorescence scanning.

The amplification of Factor VIII gene-specific sequences, obtained by polymerase chain reaction, was used for hemophilia A carrier detection. Exon 24 sequences were employed in the carrier status determination of a missense mutation causing severe hemophilia A in two unrelated patients. After agarose gel electrophoresis, the digested DNA was subjected to quantitative determination of fluorescence. This technique significantly improves the digest analysis.

Base Sequence

Human papillomavirus (HPV) cervical lesions: results from 300 Italian women studied with DNA hybridization techniques and morphology.

Human papillomavirus cervical infection was investigated in a series of 300 unselected women by comparing morphological diagnoses (cytology and histology) with results of DNA hybridization techniques (filter in situ hybridization of DNA from exfoliated cervical cells and Southern blot analysis of HPV-DNA in cervical biopsy specimens). The prevalence of HPV cervical infection diagnosed by PAP smears was 11.6%. Despite disadvantages, filter in situ hybridization was confirmed to be particularly useful for screening purposes to detect HPV in cervical scrapings. In 3 cases it was the only applicable method for diagnosing "high-risk" HPV infection. Southern blot hybridization of tissue DNA with HPV 16-DNA revealed the presence of this virus in 8 cases, and HPV 31-DNA and HPV 42-DNA in 1 case each.

Cervix Uteri

[Health status of journalists and organization of work in a national daily newspaper].

A multidisciplinary investigation was performed on 173 reporters (53 men and 20 women) of a newspaper. The microclimate and illumination conditions of the main seat, in which the use of VDT was beginning, were satisfactory, although not all the instruments were correctly adjusted. A very low percentage of reporters working in the main center was suffering from arterial hypertension indicating the presence of the "healthy worker effect". The values of plasma cortisol and arterial blood pressure of 10 reporters of the main seat, except two cases, changed normally during the evening hours. It is to point out that among the reporters there was significant correlation between spondylosis and astigmatism. The psychological investigation evidenced that the reporters were aggressive, eager of success and with constant attention. The EMG biofeedback demonstrated in the reporters with a more prolonged period of employment nervous tension and difficulty in relaxing. Particularly, in the reporters of the main center, the Stait-Trait Anxiety Inventory was more altered than in those of the peripheral seats.

Adult

Usefulness of the TRH test in the management of patients with differentiated thyroid cancer.

Thirty patients thyroidectomized for differentiated thyroid cancer were studied. Serum TSH was assayed in basal conditions and after TRH stimulation, while patients were in suppressive therapy with thyroid hormones. The basal TSH was normal in all the patients and less than 2 microU/ml in 20 patients. The TRH test was negative (no TSH response) in 27 patients and in all the cases with the basal TSH lower than 2 microU/ml.

Adult

Papillary carcinoma of the thyroid. A clinicopathologic study of 241 cases treated at the University of Florence, Italy.

A clinicopathologic study of 241 cases of papillary thyroid carcinoma treated at the University of Florence Medical School, Florence, Italy is presented. The features of greatest prognostic value were patient's age at presentation, small tumor size, total encapsulation, extrathyroid extension, multicentricity, and presence of distant metastases. The prognosis of the disease was not influenced by the pattern of tumor growth, presence of solid areas, initial presence or subsequent development of cervical lymph node metastases, type of initial thyroid operation, performance of neck dissection, or prophylactic administration of radioactive iodine. It is concluded that conservative thyroid surgery in the form of lobectomy, without neck dissection or prophylactic administration of iodine 131 (131I), constitutes adequate therapy for most cases of papillary thyroid carcinoma. More extensive therapy should be considered for older patients and for those in whom the tumor exhibits extrathyroid extension or easily detectable multicentricity.

Adolescent