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Biomedical subjects

D Lauro

Publications and source records attributed to D Lauro.

At least 37 records · Page 2Linked to original sources

Increased expression of low-affinity insulin receptor isoform and insulin/insulin-like growth factor-I hybrid receptors in term placenta from insulin-resistant women with gestational hypertension.

Gestational hypertension is associated with insulin-resistance; insulin and insulin-like growth factor-1 (IGF-1), acting through their receptors, play a role in the growth of the feto-placental unit. Since both receptors are exposed to the maternal circulation, it has been suggested that maternal metabolic abnormalities might affect placental insulin (HIR) and IGF-1 (IGF-1R) receptors. To clarify this issue, we characterized HIR and IGF-1R in placenta at term from normal women, normoinsulinaemic women with gestational hypertension (NGH), and hyperinsulinaemic women with gestational hypertension (HGH). Insulin binding was decreased in HGH women (B/T 0.12 +/- 0.03) compared to control and NGH women (B/T 0.18 +/- 0.07, p < 0.036; and 0.22 +/- 0.5, p < 0.009 respectively). Receptor affinity was lower in HGH women (ED50 0.95 +/- 0.32 nmol/l) than control and NGH women (ED50 0.42 +/- 0.19 nmol/l, p < 0.01; and 0.40 +/- 0.1 nmol/l, p < 0.007, respectively), whereas low-affinity Ex11+ isoform was higher in HGH women (Ex11+ 50 +/- 7, %) than in control and NGH women (Ex11+ 34 +/- 9%, p < 0.001; and 39 +/- 4%, p < 0.01, respectively). Increased expression of Ex11+ isoform was correlated with ED50 (r = 0.71; p < 0.002) and insulinaemia (r = 0.70, p < 0.002). IGF-I binding was increased in HGH women (B/T 0.17 +/- 0.03) compared to control and NGH women (B/T 0.09 +/- 0.05, p < 0.002; and 0.11 +/- 0.03, p < 0.002, respectively). IGF-IR affinity was similar in the three groups. The percentage of insulin/IGF-I hybrid receptors was increased in HGH women (85 +/- 3%) compared to control and NGH women (68 +/- 7%, p < 0.001; and 63 +/- 9%, p < 0.001, respectively), and was positively correlated with insulinaemia (r = 0.62, p < 0.018), ED50 of insulin binding (r = 0.62, p < 0.05), and maximal IGF-I binding (r = 0.69, p < 0.004); whereas it was inversely correlated with maximal insulin binding (r = -0.69, p < 0.004). Results provide the first evidence for altered expression of insulin/IGF-I hybrids found in insulin-resistance states.

Adult↗

[Appearance in 2 brothers of double primary neoplasms: right renal carcinoma and gastric adenocarcinoma].

We report a clinical case of a double primitive tumour (right kidney clear cell carcinoma and gastric carcinoma) in two brothers. There is no history of cancer in the parents. Both patients were previously affected by gastric ulcer. No report of association between the two neoplasms was found in literature. The age of the patients (61 and 70 years) and the singleness of the kidney tumour seem to exclude the case of a familial kidney cancer. The neoplastic transformation of the gastric ulcer is instead a quite frequent report with an incidence of about 1%. Alterations of oncogenes or tumour suppressor genes shared from both neoplasm are at present still unknown. Nevertheless molecular analysis of patients' neoplastic genome could point out typical chromosome translocations/deletions or gene mutations.

Adenocarcinoma↗

Cell proliferation of breast cancer evaluated by anti-BrdU and anti-Ki-67 antibodies: its prognostic value on short-term recurrences.

The prognostic value of breast cancer proliferative activity was evaluated in 385 women operated for primary, non-metastasised mammary carcinoma. Cell kinetics was measured using two immunohistochemical techniques. Cells in S-phase of cell cycle were labelled in vitro by incubation of fresh tissue fragments with 5-bromo 2-deoxyuridine (BrdU), a thymidine analogue. Nuclei of cells in active DNA synthesis were stained by an anti-BrdU monoclonal antibody (Mab). Cells in interphase and mitosis were detected with Ki-67, a Mab that is known to react with a nuclear antigen present in G1/S/G2/M phases of cell cycle, but not in resting cells. This reagent provides a means of evaluating the growth fraction of neoplastic cells. BrdU was incorporated in a proportion of tumour cells ranging from 0.1 to 65.5% (median 6.8%). In the panel of tumours presented in this report the median percentage of Ki-67 positive cells (Ki-67 score) was 9.0% (range 0.1-77%). The relationship between disease-free survival (DFS), BrdU labelling index, Ki-67 score and 13 different clinico-pathological variables was investigated by multivariate analysis, using the Cox proportional hazards model. Axillary node status (P = 0.009) and Ki-67 score (P = 0.038) emerged as independent prognostic factors. Nodal status and tumour growth fraction allowed division of patients into groups at different risk of relapse: tumours with a proliferative index below the median value showed a lower recurrence rate than tumours with a high proliferative activity (P < 0.001). In particular, no relapse occurred in pN0 patients bearing carcinomas with a Ki-67 labelling < 9.0% 4 years after surgery. These findings suggest that the evaluation of proliferative activity in breast cancer enhances the probability of correctly predicting outcome after surgery and could be of assistance in the planning of adjuvant therapies.

Adult↗

Loss of heterozygosity on chromosome 17p13 in breast carcinomas identifies tumors with high proliferation index.

The capacity of breast tumor cells to proliferate is considered a potential prognostic factor together with other histopathologic parameters. The authors determined the proliferation index on a large panel of human primary breast tumors by measuring the levels of incorporation of bromodeoxyuridine (BrdU) by fresh tumor specimens in culture. Previous analysis showed that the percentage of cells entering the S-phase of the cell cycle strongly correlates with tumor grade, tumor size, and estrogen and progesterone receptor status. The capacity of tumor cells to proliferate might be associated with specific genetic mutations in primary tumors. To test this hypothesis, a panel of 96 human breast carcinomas, for which the BrdU labeling index (LI) was known, were tested for loss of heterozygosity (LOH) or increased copy number (ICN) at chromosomes 1q, 3p, 13q, 17p, and 18q. On chromosome 17p, LOH and ICN were observed in 27% and 12%, respectively, of the informative breast tumors. The LOH on chromosome 17p was significantly associated with tumors having an elevated BrdU proliferation index (P = 0.022). No association (P = 0.45) was observed between BrdU LI and tumor size (T2 + T3 compared with T1), tumor grade, and lymph node status. Increased copy number on chromosome 17p, LOH or ICN on 1q, and LOH on 13q14, 18q, and 3p also showed no significant correlation with cell kinetic parameters. These data are consistent with the presence of a gene or genes on chromosome 17p13 near the YNZ22.1 locus whose normal functioning is necessary for controlling breast tumor cells proliferation in vivo.

Blotting, Southern↗

Expanded services for intrauterine contraception in Sudan.

Twenty nurse-midwives in government service in the Sudan (health visitors) were trained to provide intrauterine contraceptives in a research project designed to evaluate the safety of insertion of IUDs by medical personnel who are not physicians. After training, they inserted 763 IUDs. Independent evaluation of 520 clients was conducted by obstetrician-gynecologists who found that only six (1.2%) had been incorrectly inserted. Outcomes for clients of the health visitors with respect to perforations, infections, expulsions, and pregnancies compared well with those of eight physicians who participated in the study. The research strongly supports the concept of nurse-midwife training for IUD insertions which would greatly expand the availability of family planning services and would conserve physician time and skills for problem cases.

Community Health Nursing↗

Private midwives: a new approach to family planning service delivery in Ghana.

Data on 134 private sector midwives who were educated and trained in family planning service delivery by the Ghana Registered Midwives' Association (GRMA) showed that, for most, the course was the first they had received since qualifying as a midwife. Four out of five of the new family planning clients served by these midwives were first time contraceptive users. Approximately 9% of the clients were men, most of whom requested condoms. While delivering women is still the main function of the maternity homes, it is clear that family planning services have come to represent an important element of the health care the midwives provide. A follow-up study of family planning acceptors found extremely encouraging continuation rates. In addition, a survey of the women that the midwives had delivered showed that the contraceptive prevalence rate among these women was higher than the national rate. Providing family planning services through private sector midwives has been shown to be a very successful approach in Ghana, and one that has the potential to become a pillar of the nation's overall family planning delivery programme. As several other countries in Africa also have active private sector health networks, this approach holds promise far beyond its initial success in Ghana.

Adolescent↗

[Neoplasms of the floor of the mouth. Case reports].

The authors study a group of 61 patients treated for floor of the mouth neoplasms at the Istituto di Oncologia di Torino. They confirm a high incidence of deaths in the first 2 years after treatment in patients T greater than 2 N+, and better survival in patients with stage I-II tumours. The survival does not tend to fall between 5 and 10 years after treatment.

Adult↗

[Neoplasms of the tongue. An analysis of cases].

The authors study a group of 295 patients treated for tongue neoplasms at the Istituto di Oncologia di Torino. They point out the influence of many factors on survival particularly referring to tumour size, lymph nodes metastases and tumour stage at the time of first treatment.

Adult↗

Prognostic value of CEA and ferritin assay in breast cancer: a multivariate analysis.

The prognostic significance of preoperative serum carcinoembryonic antigen (CEA) and ferritin levels was evaluated in 191 women operated for breast cancer. The influence of CEA, ferritin and another 11 clinical and pathological features on the disease-free survival was investigated in a multivariate analysis, using Cox's proportional hazard model. Axillary node status (P = 0.004), CEA level (P = 0.011), and the histological grade of the tumor (P = 0.029) emerged as independent prognostic factors. By contrast, no significant relationship was found between ferritin and disease-free survival. These three parameters were used to derive a prognostic index (I) for each patient. Multivariate analysis showed that its prognostic value was better than the value of any single factor (P less than 0.0001). The I score was used to divide patients into groups at different risk of recurrence: low, moderate and high (97.5%, 45% and 22.5% of recurrence-free patients at 3 years respectively). The data showed that the prognosis of patients with different combinations of node status and tumor grade was related to the level of CEA. Only women with very good (node-negative with well-differentiated tumors) or very bad prognosis (node-positive with four or more metastatic nodes and poorly differentiated tumors) had a disease-free survival independent of CEA values. These findings suggest that the preoperative measurement of CEA enhances the possibility of correctly predicting outcome and hence could be of assistance in the planning of adjuvant therapies.

Adult↗

Insulin receptor substrate (IRS) transduction system: distinct and overlapping signaling potential.

Insulin receptor substrate (IRS) proteins play a central role in maintaining basic cellular functions such as growth and metabolism. They act as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as the insulin receptor, and a complex network of intracellular signalling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified which differ in their subcellular distribution and interaction with SH2 domain proteins. In addition, differential IRS tissue- and developmental-specific expression patterns may contribute to specificity in their signaling potential.

Adaptor Proteins, Signal Transducing↗