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D Esposito

Publications and source records attributed to D Esposito.

54 records · Page 3Linked to original sources
PubMed1996

Signaling via the insulin-like growth factor-I receptor: does it differ from insulin receptor signaling?

The insulin and insulin-like growth factor (IGF-I) receptors while similar in structure and function serve different physiological functions in vivo. In non-disease states the insulin receptor is primarily involved in metabolic functions whereas the IGF-I receptor mediates growth and differentiation. The separation of these functions is controlled by a number of factors including the tissue distribution of the respective receptors. Modulation of the binding of the ligands insulin or IGF-I and IGF-II to their respective receptors by the local environment of the cell also offers signaling specificity mediated via the receptors. Each ligand bind to its respective receptor with high affinity. This high affinity binding is dictated by the primary sequence of both the ligand and the receptor. Furthermore IGF-binding proteins are specific for IGF-I and IGF-II thereby modulating the binding of the IGFs to the IGF-I receptor. In contrast insulin circulates unbound to any proteins and interacts in the free state with the insulin receptor. It has been postulated that downstream substrates of the activated receptors differ in their specificity for the receptors, thus lending further specificity to the actions mediated by the receptors. While a number of known endogenous substrates such as IRS-1, IRS-2 and She are utilized by both receptors, the structural differences in the beta subunits of the two receptors has lead investigators to suggest that certain substrates may be unique to each receptor. Candidate substrates which show this specificity of action have been and are being described. Full eludication of the specificities of the insulin and IGF-I signaling pathways is of interest of course for a better understanding of intercellular communication. In addition, because the closely related proteins insulin and IGF-I are used clinically, a clear understanding of the pathways activated by these agents is essential if more specific therapeutic modalities are to be developed for use in disease states.

Binding Sites↗
PubMed1994

Identification of an HP1 phage protein required for site-specific excision.

Transposon insertion mutagenesis and transformation were used to locate genes responsible for excision in the temperature phage HP1 of Haemophilus influenzae. A 6.5 kb segment of DNA near the left end of the phage genome was sequenced, and 11 new open reading frames were identified. Two face-to-face overlapping promoter sequences organized these open reading frames into two operons transcribed in opposite directions. Interruption of the first open reading frame in the rightward operon created lysogens unable to produce phages. Provision of the uninterrupted open reading frame in trans restored phage production. The gene identified by this procedure, cox, was cloned and the protein product was expressed at high levels in Escherichia coli. The Cox protein is a 79-residue basic protein with a predicted strong helix-turn-helix DNA-binding motif. Extracts induced to express high levels of Cox contained a 9 kDa protein. These extracts inhibited integrative recombination and were required for excisive recombination mediated by HP1 integrase. The HP1 cox gene location is similar to that of the homologous excisive and regulatory genes from coliphages P2 and 186. These phages appear to share a distinctive organization of recombination proteins and transcriptional domains differing markedly from phage lambda and its relatives.

Amino Acid Sequence↗
PubMed1994

The incidence of tuberculosis among North Carolina migrant farmworkers, 1991.

All locatable subjects (n = 94) for whom tuberculosis prevalence had been determined in an earlier study were tested with purified protein derivative (PPD) and control antigens, sputum sampling, and chest x-rays. Of the 46 who had been tuberculin negative (confirmed with control antigens) 3 years earlier, 2 had developed active tuberculosis in the interim and 14 (30%) were tuberculin positive. All had been engaged continuously in migrant farmwork. Lack of access to health care, an institutional feature of migrant farmwork, was significantly associated with primary infection.

Adult↗
PubMed1994

[Benign insulinoma. Efficacy of preoperative treatment for persistent hyperinsulinemia using a synthetic somatostatin analog].

We investigated the 24-hour mean blood glucose and serum insulin (IRI), C peptide (C pep) and glucagon concentrations before (pre) and after (post) continued treatment with octreotide (100 mcg three time daily by s.c. injection) in a woman, 68 years old, affected by a nine years long benign insulinoma. The blood pool to dose 24-hour mean glucose and all hormone concentrations was obtained by equal quantities of blood samples taken every 2-hour over 24-hour. The IRI, C pep, glucagon, glucose circadian pattern and IRI/glucose ratio were determined on remaining blood portions. After continued treatment with octreotide was significantly reduced the exaggerated and inappropriate insulin (pre = 77.08 +/- 23.6 microUI/ml; post = 15.19 +/- 2.3 microUI/ml; p < 0.001) and C pep secretion (pre = 4.17 +/- 0.4 ng/ml; post--1.64 +/- 0.04; p < 0.001), while the blood glucose levels were significantly elevated (pre = 40.46 +/- 3.1 mg/dl; post = 132.46 +/- 6.9 mg/dl; p < 0.001). Also glucagon levels were significantly inhibited (pre = 73.53 +/- 12.19 pg/ml; post = 46.80 +/- 9.1 pg/ml; p < 0.05). The long-acting somatostatin analogue has improved a lot IRI/glucose ratio (pre = 1.9 +/- 0.4; post = 0.12 +/- 0.04; p < 0.001). A significant positive correlation was found between IRI and C pep before (r = 0.93; p < 0.001) as well after octreotide treatment (r = 0.85; p < 0.001). A significant positive correlation (r = 0.69; p < 0.008) between IRI and glucose was observed only after octreotide treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Four-week safety and efficacy study of dorzolamide, a novel, active topical carbonic anhydrase inhibitor.

OBJECTIVE: To investigate the activity and local and systemic safety of the topical carbonic anhydrase inhibitor, dorzolamide hydrochloride. DESIGN: Four-week, double-masked, randomized, placebo-controlled, parallel, three-center study. SETTING: Referral centers. PATIENTS: Forty-eight patients with bilateral open angle glaucoma or ocular hypertension and intraocular pressure (IOP) greater than 22 mm Hg entered the study. Two of 28 patients receiving dorzolamide and two of 20 patients receiving placebo were withdrawn due to adverse experiences. INTERVENTION: Dorzolamide (2%) or placebo to each eye three times daily for 4 weeks. MAIN OUTCOME MEASURES: Diurnal IOP curves; ophthalmologic evaluations including corneal ultrasound pachymetry and endothelial cell count; and systemic evaluations including vital signs, blood chemistries, complete blood cell counts, urinalysis, electrocardiogram, and drug and carbonic anhydrase activity levels in red blood cells. RESULTS: Mean IOP at morning trough (8 AM) decreased from 27.1 mm Hg at baseline to 23.5 mm Hg on day 29 with dorzolamide (-13.3%) compared with a decrease from 27.1 mm Hg to 26.4 mm Hg with placebo (-2.3%). Peak activity occurred 2 hours after administration, with IOP decreasing from 26.8 mm Hg at baseline to 21.8 mm Hg on day 29 with dorzolamide (-18.4%) vs 26.1 mm Hg to 25.5 (-2.4%) with placebo. Mean corneal thickness was slightly increased for the dorzolamide-treated group compared with the placebo-treated group (0.009 mm vs 0.001 mm, respectively, P < .05) and changes in endothelial cell counts were similar (-24 cells/mm2 vs -27 cells/mm2, respectively, P > .25). Mean carbonic anhydrase isoenzyme II activity in red blood cells decreased to 21% of baseline in dorzolamide-treated patients. There were no clinically significant differences in ocular or laboratory parameters between the dorzolamide and placebo groups. CONCLUSIONS: Dorzolamide demonstrated significant IOP lowering activity over 4 weeks. It was well tolerated and there were no clinically significant changes in ocular or systemic safety parameters.

Administration, Topical↗
PubMed1992

TGF beta inhibits rat thyroid cell proliferation without alterations in the expression of TSH-induced cell cycle-related genes.

Transforming growth factor beta (TGF beta) is a secreted polypeptide factor that is thought to play a major role in the regulation of proliferation of many cell types and various differentiation processes. TGF beta acts on thyroid cells by inhibiting cell proliferation and expression of differentiation markers, such as thyroglobulin production and iodide uptake. Exponentially growing thyroid cells cultures accumulate mostly in G0/G1 after exposure to TGF beta for 48 hours. TGF beta inhibits the TSH induced transition of quiescent thyroid cell from the G0 to the S phase. These effects on the thyroid cell growth, however, are not mediated by changes in the TSH-induced cell cycle-related genes expression; both immediate early and progression genes expression is unaffected by the TGF beta treatment.

Animals↗
PubMed1992

Tetanus immunity in a partially vaccinated population of children in a district of Naples (Secondigliano).

A general opinion is that compliance with the compulsory immunization programme of children is excellent in Italy. We have studied antitetanus immunity in relation to vaccination history in a sample of 444 school children born between 1977 and 1981 in a district of Naples. Information on vaccination history was collected by interviewing the parents and validated using the official vaccination certificates. Titration of antibodies against tetanus was carried out by the immunoenzymatic method. 0.9% of our study subjects had not been vaccinated at all and only 21.2% had received 4 vaccine doses. In 18 children the presence of antitetanus antibodies was not detected; 14 of them had received one or more doses of vaccine. The lack of compliance with the vaccination programme was associated with a remarkable delay in administering the tetanus vaccine. In the population reported here, the percentage of subjects only partially covered is higher than that found in other regions of Italy.

Child↗
PubMed1989

Decline in the exposure to hepatitis A and B infections in children in Naples, Italy.

In May 1988, the hepatitis A antibody (anti-HAV) and hepatitis B virus (HBV) markers were studied by radioimmunoassay in 484 apparently healthy children between the ages of 7 and 12, attending a primary school in Naples, Italy. The overall anti-HAV prevalence was 11.2%, increasing from 5.2 in 7-year-old children to 28.2% in children between the ages of 11 and 12 years old. The overall prevalence of the hepatitis B surface antigen (HBsAg) and of other HBV markers were 0.8 and 6.8 respectively. Compared with a similar previous study conducted in Naples in 1980, the results show a significant reduction in the prevalence of anti-HAV in each of the two age-groups (P less than 0.01), in the prevalence of any HBV marker in the 11 to 12-year-old group, as well as in the total population (P less than 0.05). The findings of the present study indicate that today, children in Naples are less exposed to the hepatitis A virus than in the past, most likely because of improvements in both the socioeconomic conditions and in health education during recent years. These same reasons, as well as decreased family size and a lower prevalence of HBeAg among HBsAg carriers could explain the decline, although to a lesser degree, of exposure to HBV infection.

Child↗
PubMed1989

Chromosomes of older humans are more prone to aminopterine-induced breakage.

We have adopted a simplified version of the "cell hybrid cotransfer method" to test the hypothesis that human lymphocytes derived from elderly individuals have a higher chromosome instability. Peripheral blood lymphocytes from "old" male individuals and "young" controls were fused with a Chinese hamster cell line (CHO-YH21), yielding 10 HAT-resistant rodent-human clones from the old propositi and 22 from the young controls (HAT = hypoxanthine/aminopterin/thymidine). Both series of hybrid clones were analyzed with respect to the retention of the enzyme glucose-6-phosphate dehydrogenase and the surface antigen MIC2 identified by monoclonal antibody 12E7, two human X chromosome-linked markers located at opposite ends of the X chromosome. Cell hybrid clones with an X chromosome from a young control retained both markers in about 70% of the cells. In contrast, cell hybrid clones with an X chromosome from an old donor retained the MIC2 marker in only 30% of their cells. Slot-blot hybridization studies have established that the observed loss of the MIC2 marker is due to loss of the coding gene, not to suppression of its expression. Similar hybridization studies with molecular probes specific for other regions of the X chromosome suggest preferential chromosomal breakage sites. T lymphocytes from old donors were also found to have an LD50 for aminopterine significantly lower than the concentration of this drug in the HAT medium used to grow the hybrids, suggesting that the higher level of gene loss observed in the X chromosomes from old donors may be directly related to their increased sensitivity to the clastogenic effect of aminopterine. We speculate that the higher rate of chromosomal breakage and of marker loss observed along the "old-age" X chromosomes could be the result of "molecular scars" accumulated with aging at sites of constitutive chromosomal fragility.

Adult↗
PubMed1985

The human genes for hemophilia A and hemophilia B flank the X chromosome fragile site at Xq27.3.

Two DNA recombinant clones, shown by separate studies to contain DNA sequences homologous to the genes coding for the human blood coagulation Factors VIII and IX, were hybridized in situ to metaphases or prometaphases derived from patients with the fragile-X syndrome and from a normal control. The results of these experiments indicate that (i) both genes are located in the subtelomeric region of the long arm of the human X chromosome flanking the fragile site at Xq27.3, (ii) the resolution of this localization is approximately 0.5% the length of the human haploid genome, i.e., 1.8 X 10(7) bp, (iii) the linear order of loci within the above region is Factor IX-fragile site-Factor VIII-Xqter. Both the localization and the linear order of these loci have been confirmed by Southern blotting studies using the same molecular probes and a panel of rodent-human somatic cell hybrids known to have retained different segments of the human X chromosome. The findings described herein and the knowledge that Factor IX deficiency recombines freely with at least two loci of the G6PD cluster support our hypothesis that the chromosomal region which includes the fragile-X site is normally a region of high meiotic recombination.

Chromosome Mapping↗
PubMed1985

Genes controlling gp25/30 cell-surface molecules map to chromosomes X and Y and escape X-inactivation.

The monoclonal antibody AbO13 defines a cell-surface antigen that is expressed on most cultured human cells, but not on rodent cells. AbO13 precipitates glycoproteins of 25,000 and 30,000 mol. wt. from lysates of [3H]glucosamine-labeled human cells. Results of the serological typing of a panel of 25 rodent-human somatic cell hybrid clones show that reactivity with AbO13 segregates with the human X and Y chromosomes. The presence of either of these chromosomes is sufficient for O13 expression on the hybrid cell surface. Analysis of hybrid clones containing human X chromosomes with karyotypically defined deletions permitted the regional assignment of the X-linked gene locus controlling the expression of O13 to Xp22-pter. In addition, AbO13 is reactive with Chinese hamster-human hybrids derived from fibroblasts of a 49,XXXXX individual that contained only inactivated copies of the human X chromosome. These results suggest that the X-linked locus determining the expression of O13 is not subject to X-inactivation.

ABO Blood-Group System↗
PubMedDate not supplied

Plasma glucose level decreases as collateral effect of fermented papaya preparation use.

AIM: Fermented Papaya Preparation (FPP) is a natural healthy drug that has been commercially sold in Japan and Philippines. This nutricetive, bio-normalizer product has antioxidant action, inhibitory effect on oxidative DNA damage and tissue injury, being a potent OH scavanger. The wide use of FPP, expecially by elderly people, made us note an unknown collateral effect, i.e., blood sugar level dropping signs especially in the afternoon. The aim of the present work was to scientifically verify the possibility that individuals, who are taking the nutriceutical FPP, might have a decrease of plasma sugar levels. MATERIALS AND METHODS: For this purpose, 50 subjects, divided in two groups, were enrolled. The first group was made of 25 patients: 13 females and 12 males affected by type-2 diabetes mellitus under treatment with the oral antidiabetic drug, glybenclamide. The control group included 25 clinically-healthy subjects: 16 females and 9 males, matching in age. All subjects were given 3 grams of FPP daily, during lunch, for two months. RESULTS: The results of this study confirmed the empirical experience that FPP use can induce a significant decrease in plasma sugar levels in both healthy subjects and type 2 diabetic patients. This hypoglycaemic effect, associated with clinical signs, induced the diabetic patients to reduce the dosage of their antidiabetic oral therapy (in one patient the therapy was really suspended). CONCLUSIONS: In accordance with these results, the FPP administration is suggested as an adjuvant drug to join the oral antidiabetic therapy in type 2 diabetes meltus.

Aged↗
PubMedDate not supplied

[Geriatric questionnaire assessment in the sanitary district 50 of the ASL NA1].

In this study it has been estimated the prevalence of the disability in the over 65 population, resident in the sanitary district 50 of the ASL NA1. The aim is an appropriate nursing planning based on the needs of the population. The used geriatric questionnaire is provided by law (ex art. 70 comma 1 lettera a. del DPR 270/2000). The general practitioners of the district filled in 6014 questionnaires. The elders that resulted as self-reliant at the ADL and self-sufficient at the IADL are 86.9% and 80.2% respectively. 54.9% of the elders are free from slight or heavy depression. 81.7% are not going to have mental worst damage. Depression is statistically related to a low income and to a low level of self-reliance and self-sufficiency at the ADL and IADL questionnaire. The study evaluated important formative needs of the elders and pointed out some issues regarding the questionnaire structure and its filling in.

Activities of Daily Living↗