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Biomedical subjects

A Bianchi

Publications and source records attributed to A Bianchi.

At least 19 recordsLinked to original sources

Pituitary tumor-transforming gene 1 and endocrine cancers: an up-to-date review through history, current insights and future perspectives.

Pituitary tumor-transforming gene 1 (PTTG1), discovered in 1997 by Pei and Melmed, takes part in cellular replication, cell cycle control, DNA repair mechanisms, organogenesis, metabolism regulation, cellular transformation, and senescence. Its biological actions include protein-protein interactions, modulation of gene transcription, and other than intracellular and autocrine mechanisms, even paracrine activities. For the reasons mentioned above, PTTG1 stands out as a multifaceted regulator of cancer biology; it is involved in genomic and chromosomal instability, local invasiveness, neo-lymphangiogenesis, and metastatic spreading. In solid neoplasms, endocrine neoplasms, although deemed rare, have experienced a significant increase in diagnostic incidence in recent years. Endocrine cancers are still a major challenge in healthcare and research since several questions remain unanswered, even though researchers have made considerable efforts to uncover their causes. Twenty-seven years have passed since PTTG1's discovery, and several works have been published. However, only the tip of the iceberg has been unveiled. Herein, we review current knowledge of PTTG1's action in endocrine cancers, such as pituitary, thyroid, testicular, adrenal, pancreatic, and ovarian.

Humans

[Asymptomatic carriage of Chlamydia trachomatis in men consulting for condylomata acuminata].

A search for Chlamydia trachomatis by cell culture was carried out in the urethra of 82 male patients consulting for condyloma acuminata at the Clinical and Biological Centre for Sexually Transmissible Diseases of the Saint-Louis hospital, Paris. Three patients had discreet urethral signs, but none had urethral discharge. Cell culture was positive for C. trachomatis in 36 of the 82 patients (44 percent). This high prevalence suggests that C. trachomatis should systematically be looked for in the urethra of male patients consulting for condylomata acuminata. If this cannot be done, then a systematic treatment with tetracyclines should be instituted.

Adult

Acetyl-CoA carboxylase in Reuber hepatoma cells: variation in enzyme activity, insulin regulation, and cellular lipid content.

Reuber hepatoma cells are useful cultured lines for the study of insulin action, lipid and lipoprotein metabolism, and the regulation of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid biosynthesis. During investigations in different clonal lines of these cells, we have uncovered marked intercellular variability in the activity, enzyme content, and insulin regulation of ACC paralleled by differences in cellular neutral lipid (triglyceride) content. Two contrasting clonal lines, Fao and H356A-1, have been studied in detail. Several features distinguish these two lines, including differences in ACC activity and enzyme kinetics, the content of the two major hepatic ACC isozymes (Mr 280,000 and 265,000 Da) and their heteroisozymic complex, the extent of ACC phosphorylation, and the ability of ACC to be activated on stimulation by insulin and insulinomimetic agonists. As studied by Nile Red staining and fluorescence-activated cell sorting, these two lines also display marked differences in neutral lipid content, which correlates with both basal levels of ACC activity and inhibition of ACC by the fatty acid analog, 5-(tetradecyloxy)-2-furoic acid (TOFA). These results emphasize the importance of characterization of any particular clonal line of Reuber cells for studies of enzyme regulation, substrate metabolism, and hormone action. With respect to ACC, studies in contrasting clonal lines of Reuber cells could provide valuable clues to understanding both the complex mechanisms of intracellular ACC regulation in the absence and presence of hormones and its regulatory role(s) in overall hepatic lipid metabolism.

Acetyl-CoA Carboxylase

Evaluation of a chemiluminometric immunoassay for detection of Chlamydia trachomatis in the urine of male and female patients.

A chemiluminometric immunoassay (Magic Lite Chlamydia) for detection of Chlamydia trachomatis antigens in first-void urine samples was compared with cell culture using urogenital swabs from 221 men and 242 women. The rate of isolation of Chlamydia trachomatis was 23.5% in men, nearly 80% of whom had symptoms of urethritis, and 8.3% in women, in whom both cervix and urethra samples were tested. In urine sediments from men and women respectively the chemiluminometric assay showed a sensitivity of 80.8% and 70%, a specificity of 97% and 95%, a positive predictive value of 89.4% and 58.3%, and a negative predictive value of 94.3% and 97.2%. Discrepancies between results obtained with the chemiluminometric assay and cell culture were resolved using two polymerase chain reaction techniques to test urogenital samples. The detection of Chlamydia trachomatis in urine samples with the chemiluminometric assay was confirmed to be superior for screening symptomatic men with urogenital infections than women as a lower prevalence population.

Adolescent

Delayed surgery for congenital diaphragmatic hernia: neurodevelopmental outcome in later childhood.

The long term neurodevelopmental outcome was assessed in 23 survivors born with congenital diaphragmatic hernia who had been managed by an elective delay in surgical repair after a period of stabilisation. This cohort was treated in one neonatal surgical unit between 1983 and 1989 by a single team of surgeons and anaesthetists. All children underwent comprehensive neurological, developmental, and anthropometric assessment at a mean age of 56 (range 18-94) months. Two children (9%) had major disability (one with hemiplegia and one with a lower limb monoplegia) and two further children had minor disabilities (one had partial sightedness and squint, the other squint only). The mean developmental quotient (DQ) for the group was 108 (SD 10.8) and none had developmental delay (defined as DQ < 70). Infants who had spent more time in hospital, or had had a longer duration of ventilation, tended to have lower weights and lower occipitofrontal circumference centiles in later childhood. Preoperative stabilisation and delayed surgery for congenital diaphragmatic hernia is not associated with an impaired neurodevelopmental outcome.

Child

Early prenatal diagnosis and therapy of fetal hypothyroid goiter.

We report a case of early diagnosis of iodide-induced fetal hypothyroidism at 22 weeks of gestation, confirmed at 29 weeks by cordocentesis and successfully treated intra-amniotically. The ultrasonographic feature was the presence of two echogenic masses in the fetal neck; polyhydramnios was absent. Mild hypothyroidism was diagnosed based on fetal serum obtained by percutaneous umbilical blood sampling at 29 weeks of gestation. The persistence of fetal hypothyroidism in spite of maternal thyroid improvement was confirmed by a second cordocentesis at 35 weeks of gestation, and a single injection of intra-amniotic levothyroxine (250 micrograms) was performed. The serial ultrasonographic examinations showed disappearance of the fetal goiter. A healthy female baby (3,630 g) was delivered at term. At birth, the thyroid gland was not enlarged, and neonatal thyroid hormones were within the normal range. This case suggests that cordocentesis is a reliable method to assess the fetal thyroid status; moreover a single injection of intra-amniotic thyroxine was effective in treating fetal hypothyroid goiter.

Adult

Bioavailability of two formulations of acetylsalicylic acid gums.

Bioavailability studies have been performed with ten healthy volunteers on different dosage forms of acetylsalicylic acid (ASA) in order to assess the bioavailability of two different ASA gums compared with commercial ASA tablets. The results of this study show that ASA is more readily absorbed and eliminated after administration of gum formulations than after administration of tablets, but the bioavailability obtained from the gums was lower than that observed from the tablets.

Adult

[Cerebral lesions in patients with ovarian cancer].

The Authors report the appearance of Central Nervous System lesions in three patients previously treated for ovarian carcinoma. In one case (Stage 1) the histological sample found a glioblastoma, in the others (Stage 3) the lesion was the metastases after systemic diffusion of the primary carcinoma. CNS metastases are rare and more frequently occur in advanced ovarian carcinoma. In patients at Stage 1, CNS isolated lesions may be primary tumors.

Aged

[A cellular proliferation study in patients with colorectal cancer, solitary, synchronous and with polyps].

Colonic carcinogenesis is probably related to a disturbance in cell proliferation of the colonic mucosa. The present study was designed to determine whether patients with adenomatous polyps of the colon, which have a tendency to develop synchronous malignancies of the colon, have any disturbance in mucosal cell proliferation. Using flow cytometry the proliferative index, and the S and G2M phases of normal mucosa and tumoral tissue of patients with colorectal cancer (synchronous, alone, or associated with adenomatous polyps) were studied. No differences were found between the there groups of study at the level of proliferation pattern of normal mucosa. Our findings do not support the development of synchronous or metachronous colon cancer in patients with polyps on the basis of different patterns of cell proliferation.

Aged

Surgical treatment of invasive carcinoma of the vulva. A reappraisal.

The Authors studied three groups of patients affected by invasive vulvar carcinoma. The first group (19 cases), treated by radical vulvectomy and bilateral inguinal lymphadenectomy, had a survival rate at 5 years of 89% in Stage I and 56% in Stage II. The second group (9 cases) which presented poor general health conditions, had a survival rate at 4 years of 33% and 14% in Stage I and in Stage II, respectively. The third group of patients (7 cases), who refused any type of treatment, died within 12 months. Nodal involvement influenced survival rate. In fact, regardless of the stage, a survival rate at 5 years of 92% and 26% was seen in patients with negative nodes and positive nodes, respectively. In conclusion, the study confirms that radical surgery is the therapy of choice in advanced carcinoma of the vulva. However, early diagnosis remains the most important agent in reducing the extension of the surgical treatment.

Aged

[Dermoid cyst associated with planocellular carcinoma].

The case of an ovarian mature cystic teratoma with an associated squamous cell carcinoma is described. The patient, in advanced stage, died a few months after surgery, during the treatment by chemo and radiotherapy.

Carcinoma, Squamous Cell

Alterations of the p53 tumor suppressor gene during mouse skin tumor progression.

The two-stage murine skin tumorigenesis model is widely used to study the development of squamous cell neoplasias. We have investigated expression of the p53 and retinoblastoma tumor suppressor genes in eight murine skin tumor cell lines of varied histopathology and malignant potential, in seven in vivo-derived clones from these cell lines, and in 39 primary short-term cultures of similarly induced skin tumors at various stages of tumor progression. One squamous cell carcinoma cell line and three more malignant clones derived from it revealed mutations of the p53 protein by immunoprecipitation analyses despite normal-sized p53 transcripts. Sequence analysis identified the nature of the point mutations in these lines, a G----C transversion in codon 132. Mouse retinoblastoma transcripts and protein were unaltered in all the cell lines examined. Among short-term cultures of skin tumors, the p53 gene appeared normal in all papillomas and early well-differentiated carcinomas by Southern and immunoprecipitation analyses. In contrast, four of eight tumors from later stages of promotion (50-60 weeks) possessed alterations in p53, including loss of the p53 product, and loss of immunoreactivity with a murine-specific antibody recognizing only wild-type p53 protein. Loss of heterozygosity at the p53 locus was similarly observed in several more malignant tumors from later stages of promotion. In contrast retinoblastoma expression was normal regardless of the stage of promotion or histological grade of the tumor. Direct sequence analyses of exons 5 through 8 of the p53 gene in eight advanced murine skin tumors revealed a 25% incidence of p53 mutations. These point mutations were located in codons 245 and 263. Collectively, these data indicate that alterations in the p53 gene occur in 25 to 50% of murine skin tumors induced by the two-stage tumorigenesis protocol and are later events in murine skin tumor progression. Moreover, these alterations are associated with tumors possessing a more malignant and/or poorly differentiated phenotype.

Animals

Detection of hyperreactive T cells in multiple myeloma by multivalent cross-linking of the CD3/TCR complex.

Cellular immunity was investigated in 43 patients with multiple myeloma (MM) by assessing 3HTdR uptake induced by monocyte-dependent [CD3 monoclonal antibodies (MoAbs), phytohemagglutinin (PHA)] and monocyte-independent (CD2 MoAbs, ionomycin + phorbolester) stimulations. The former were evaluated in peripheral blood mononuclear cells (PBMNC) and purified T cells; the latter were evaluated in purified T-cell preparations only. MM showed significantly lower PBMNC responses to PHA (P less than .001), soluble OKT3 (CD3) (P = .01), and immobilized OKT3 MoAbs (P = .01). On purification of T cells, MM responses were still defective to soluble T11(2) + T11(3) (CD2) MoAbs (P = .004), phorbol myristate acetate (PMA) plus ionomycin (P less than .001), but significantly higher to plastic-immobilized OKT3 (P = .004). In some MM, 3HTdR uptake, interleukin-2 (IL-2) receptor (CD25) expression, and IL-2 production were as high on stimulation with plastic-immobilized OKT3 as that observed in normal subjects under optimal conditions (ie, plastic-immobilized OKT3 plus accessory signals). CD3 hyperreactivity correlated with the number of CD8+ HLA-DR+ cells in MM T-cell preparations. MM patients with more than 10% CD8+ HLA-DR+ cells had significantly higher responses to immobilized OKT3 (P less than .001), but lower responses to T11(2) plus T11(3) (P = .01), and PMA plus ionomycin (P = .03) than patients with less than 10% CD8+ HLA-DR+ cells. Phenotyping of CD45RA (naive) and CD45R0 (memory) expressions in resting MM T cells showed a lower ratio of CD45RA to CD45R0 in both CD4 (P less than .05) and CD8 (P less than .001) subpopulations. These data indicate that (a) some MM T cells require significantly fewer accessory signals (if any) to express the IL-2 receptor fully, secrete IL-2, and proliferate on multivalent cross-linking of the CD3/TCR complex; and (b) this peculiar state of activation is associated with high HLA-DR expression in CD8+ lymphocytes.

Aged

Increased survival, limb preservation, and prognostic factors for osteosarcoma.

Preoperative intraarterial (IA) cisplatin (CDP) was administered to 92 patients with nonmetastatic osteosarcoma. The ages of the patients ranged from 4 to 28 years. Sixty-four patients (70%) received 2 or 3 preoperative courses and 28 (30%) received 4 or more. Sixty-two specimens were available for pathologic examination to assess the degree of tumor necrosis. More than 90% tumor destruction was observed in 16 of 42 patients (38%) who received 1 to 3 preoperative courses as opposed to 17 of 20 (85%) who received 4 or more courses. Patients who received 4 or more courses had a 2-fold probability of achieving more than 90% tumor necrosis, and 68% underwent conservative surgery. Of those who received 3 or less courses, 23% underwent conservative surgery. Postoperatively, patients were treated with intravenous (IV) CDP alternating with doxorubicin (ADR) (Adriamycin, Adria Laboratories, Columbus, OH). Pulmonary metastases developed in 36 patients, bone metastases in 2, and local recurrence in 6. Two patients died of cardiac failure without evidence of disease. Thus, 46 patients (50%) were continuously free of disease 18 to 78 months after diagnosis. Univariate and multivariate analyses showed that male sex, low grade preoperative chemotherapy-induced necrosis, and nonosteoblastic histologic condition were prognostic factors predictive of recurrence, while male sex and large tumor size were prognostic factors predictive of death. These results are comparable with those reported by other centers and are superior to our previous experiences that yielded survival rates of 5% to 10%. A substantial number of patients also had the opportunity to achieve tumor removal with conservative surgery.

Adolescent

Promoter independence as a feature of most skin papillomas in SENCAR mice.

In the present study, the fate of individual papillomas induced by initiation-promotion on the backs of SENCAR mice was monitored after discontinuation of limited promoter treatment. Groups of 40 SENCAR mice each were initiated by a single topical application of 7,12-dimethylbenz[a]anthracene (DMBA) at 2, 1, 0.5, or 0.25 micrograms/mouse. Animals were promoted with 2 micrograms of 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly during 10 weeks. At that time point, 10 papilloma bearing mice from each group were randomly selected to follow the growth of their existing tumors. Animals and their individual tumors were identified, charted, and photographed weekly. After an initial increase, the average number of papillomas/mouse remained constant after discontinuation of TPA in all the groups except the group receiving the highest DMBA dose (Group 1) and with highest tumor load. Twenty-one weeks after TPA was discontinued, only 10-20% of the papillomas had regressed and no statistically significant differences were found among the different DMBA dose groups. On the other hand, Group 1 showed the highest percentage of coalescing tumors which was apparently a function of tumor load. In addition, no differences were observed in the proportion of positive tumors with activating point mutations at codon 61 of the Ha-ras gene when comparing samples of papillomas from the highest DMBA initiation dose group (2 micrograms) versus the lowest DMBA initiation dose group (0.25 micrograms). Our present data suggest that papillomas induced with low doses of DMBA in SENCAR mice are no more TPA dependent than those induced by higher initiating doses. Furthermore, in SENCAR mice at the doses used in the present study (0.25-2 micrograms/mouse), the number of so-called "promoter dependent" papillomas represents only a small percentage of the total papillomas produced using the initiation-promotion protocol.

9,10-Dimethyl-1,2-benzanthracene