Biomedical subjects

A Caruso

Publications and source records attributed to A Caruso.

At least 199 records · Page 11Linked to original sources

PubMed1995

Aspects of molecular interaction between HIV p17 and human gamma interferon.

We describe the specific interaction between high-purity recombinant human immunodeficiency virus (HIV) type 1 p17 and human gamma interferon (hIFN-gamma) proteins. This interaction was found to be dose dependent and to involve conformational epitopes on both sides. Specificity was confirmed by competition ELISA, using monoclonal antibodies (MAbs) to hIFN-gamma as specific reagents. By competition experiments we also identified the epitope(s) on the hIFN-gamma molecule involved in p17 binding, very close to the receptor binding site. The kinetic constants were determined by surface plasmon resonance (SPR) analysis. The affinity constant (KA) of the complex was 2.78 x 10(8) M-1, that is, the ratio between a low dissociation rate constant (Koff)(1 x 10(-5)sec-1) and a high association rate constant (Kon) (3 x 10(3) M-1sec-1). However, p17 did not displace the binding of hIFN-gamma to its cellular receptor, nor did it interfere with the capability of the lymphokine to induce de novo expression of HLA-DR antigens on human monocytic cells or to inhibit the proliferation of tumor cells.

Animals↗

PubMed1995

A monoclonal antibody to the NH2-terminal region of human interferon-gamma inhibits its antiproliferative activity without affecting its internalization.

MAb IGMB-15, an anti-hIFN-gamma MAb, neutralizes the antiproliferative activity of hIFN-gamma without affecting that of hIFN-alpha or hIFN-beta. The neutralizing capacity of MAb IGMB-15 is wide: it has been assessed on cell lines whose origin and sensitivity to hIFN-gamma differ. The binding of hIFN-gamma to its receptor and its subsequent internalization into the target cell were not influenced by the antibody. MAb IGMB-15 has been found to interact with hIFN-gamma in solution but not when the lymphokine was associated with its cell surface receptor, showing that the growth of certain cell lines can be inhibited at the cell membrane level. This finding is consistent with the existence of an accessory factor responsible for the antiproliferative activity of hIFN-gamma.

Antibodies, Monoclonal↗

PubMed1995

The growth hormone response to growth hormone-releasing hormone is blunted in polycystic ovary syndrome: relationship with obesity and hyperinsulinaemia.

This study was designed to investigate the growth hormone (GH) secretory response to the growth hormone-releasing hormone (GHRH) test in women with polycystic ovary syndrome (PCOS). A total of 25 patients with PCOS (13 obese and 12 non-obese) and 15 normal ovulatory women (seven obese and eight non-obese) were included in this study. In the follicular phase patients were subjected to an oral glucose tolerance test (OGTT); 2 days later they underwent a GHRH test. Basal plasma concentrations of gonadotrophins, steroids and sex hormone-binding globulin were measured. Insulin and GH were assayed under the OGTT and GHRH test respectively. Based on the insulin response to OGTT in the PCOS group, nine patients were classified as normoinsulinaemic and 16 as hyperinsulinaemic; none of the patients of the control group had a hyperinsulinaemic response to OGTT. Obese patients showed a trend towards a lower GH response to GHRH. Moreover, hyperinsulinaemic patients showed a significantly (P < 0.05) lower area under the curve for secretion of GH (AUC-GH) as compared to normo-insulinaemic patients. All PCOS patients exhibited a markedly decreased response of GH to GHRH compared with the control population. Obese and hyperinsulinaemic PCOS patients were both found to have a lower response of GH to GHRH than all other groups. Despite the fact that obesity and hyperinsulinaemia have an additive influence on the impairment of GH secretion, our results suggest that other factors may also negatively affect GH secretion in PCOS.

Adult↗

PubMed1995

Epidermal growth factor receptors in placentae and fetal membranes from hypertension-complicated pregnancies.

Epidermal growth factor receptor concentrations (EGFR) in placentae and fetal membranes from 25 normal and 25 hypertension-complicated pregnancies were analysed by a radioreceptor technique. Higher EGFR concentrations were found in placentae from hypertension-complicated pregnancies than in those from normal pregnancies (median 125.0 fmol/mg protein, range: 33.4-190.7 versus median 50.3 fmol/mg protein, range 21.4-184.0) (P = 0.0002). EGFR concentrations were significantly lower in fetal membranes than in placental tissue, both in normal membranes (median 31.7, range 4.8-92.0 versus median 50.3, range 21.4-184.0) (P = 0.0004) and in hypertension-complicated pregnancies (median 65.0, range 16.8-125.0 versus median 125.0, range 33.4-190.7) (P = 0.0001). A statistically significant inverse correlation between EGFR concentrations and gestational age was found in placentae (r = 0.53, P = 0.0061) and fetal membranes (r = 0.56, P = 0.0032) from hypertension-complicated pregnancies. Multiple regression analyses demonstrated that hypertensive disease is more closely associated with EGFR concentrations than gestational age and fetal weight in placental tissue and fetal membranes. Our findings suggest that hypertensive disorders in pregnancy are associated with elevated EGFR concentrations in both the placenta and fetal membranes.

Epidermal Growth Factor↗

PubMed1995

Effect of opioid blockade on insulin metabolism in polycystic ovarian disease.

A total of 17 women affected by polycystic ovarian disease (PCOD) were studied to evaluate the involvement of endogenous opioids in the pathophysiology of the hyperinsulinism in PCOD by administering naltrexone, an oral opioid antagonist. An oral glucose tolerance test (OGTT) was performed at baseline (on day 5 of the cycle) and repeated after 6 weeks of naltrexone administration. Plasma glucose, insulin and connecting peptide (c-peptide) concentrations were evaluated in all samples. Based on their insulinaemic response to OGTT, patients were classified as hyperinsulinaemic or normoinsulinaemic. Naltrexone treatment significantly (P < 0.007) reduced the insulin response to OGTT in the hyperinsulinaemic group without affecting the c-peptide incremental area; in the normoinsulinaemic group there was a slight, but not significant, increase in both c-peptide and insulin incremental areas. The two groups showed similar c-peptide incremental areas after naltrexone treatment. There was no significant difference in the c-peptide:insulin incremental areas molar ratio between the two groups; after treatment, a significant increase in this ratio was observed in both groups. When we considered the data as an expression of the fractional hepatic extraction of insulin, we found a lower value for hyperinsulinaemic in comparison with normoinsulinaemic patients (not significant), and a significant (P < 0.01) improvement of this parameter in the hyperinsulinaemic group after naltrexone administration. In conclusion, we suggest that the contribution to hyperinsulinaemia in PCOD patients may be at least in part due to both increased pancreatic secretion and reduced hepatic removal of insulin. Chronic pharmacological inhibition of opioid tone could improve the insulin plasma concentration by acting chiefly on the liver metabolism of insulin in hyperinsulinaemic patients.

Adolescent↗

PubMed1995

Increased levels of antibodies to IFN-gamma in human and experimental African trypanosomiasis.

In African trypanosomiasis the occurrence of antibodies to interferon-gamma (IFN-gamma) was studied in both humans and experimental rats. Sera from patients infected with Trypanosoma brucei gambiense showed increased levels of antibodies to IFN-gamma as compared with controls from the same regions in Africa. In Sprague-Dawley rats infected with Trypanosoma brucei brucei an early appearance of IFN-gamma-producing spleen cells was observed, followed by an increase in levels of antibodies against IFN-gamma in the sera. Previously, IFN-gamma has been found to play a crucial role in trypanosome infections in rats by promoting proliferation of Trypanosoma brucei brucei. The appearance of antibodies to IFN-gamma in humans, as in rats, indicates that this cytokine is produced also in the human infection. Its parasitic growth-stimulating and pathophysiological effects on the organism may be reduced by the antibodies.

Animals↗

PubMed1995

Nerve growth factor promotes the differentiation of pituitary mammotroph cells in vitro.

It is well known that the differentiation of somatotroph cells is dependent on GRF. The extracellular signals that direct the initial proliferation and differentiation of mammotroph cells during pituitary development, however, have remained elusive. In the present study we first report that somatomammotroph and mammotroph cells present in early postnatal rat pituitary cultures express the receptor for nerve growth factor (NGF) and contain NGF. In addition, we demonstrate that endogenous NGF supports the proliferation and terminal differentiation of mammotroph cells during postnatal in vitro maturation. Early postnatal rat pituitary cells were cultured for 1-12 days, double stained with antibodies to PRL and GH, and analyzed by fluorescence-activated cell sorting. Mature mammotroph cells were generated in culture as shown by 1) the increase in PRL production, 2) the spreading of cells secreting only PRL in relation to those producing both PRL and GH, and 3) the expression of D-2 receptors for dopamine. Exposure of cell cultures to NGF produced a remarkable increase in the rate of appearance of mammotroph cells and an increase in their abundance from 20 +/- 0.5% to 44 +/- 1%. Deprivation of secreted NGF by means of a specific antibody completely prevented the generation of mature mamotrophs. The fluorescence-activated cell sorting analysis of cells grown in the presence of the antibody to NGF showed, in fact, that although the proportions of somatotrophs and somatomammotrophs were unchanged, that of mammotrophs was much lower than that in untreated cultures. We, thus, conclude that NGF is critical for generation of the mammotroph phenotype during pituitary maturation.

Animals↗

PubMed1995

Evidence of a distinct derangement of opioid tone in hyperinsulinemic patients with polycystic ovarian syndrome: relationship with insulin and luteinizing hormone secretion.

Recent data indicate that an altered opioid tone could be involved in the LH hypersecretion and metabolic alterations seen in polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the presence of a common mechanism of action of opioids on altered insulin and gonadotropin release in patients suffering from PCOS. Twenty-eight women affected by PCOS and 8 normal ovulatory women were studied; an oral glucose tolerance test (OGTT) and GnRH tests were performed during the follicular phase before and after 6 weeks of naltrexone treatment (50 mg/day, orally). Plasma levels of sex hormone-binding globulin and steroids were assayed in the basal samples, whereas FSH and LH were analyzed during the GnRH stimulus. Insulin and glucose were assayed by the OGTT. Based on the insulinemic response to OGTT, 17 women were classified as hyperinsulinemic and 11 as normoinsulinemic. No difference in glucose and hormone plasma concentrations was observed before and after naltrexone treatment in both groups. Only basal sex hormone-binding globulin values were higher in normoinsulinemic compared to hyperinsulinemic subjects. Administration of the opioid antagonist significantly reduced the insulin response to OGTT only in the hyperinsulinemic group. No difference were found in the LH increment after the GnRH stimulus in both group of patients before treatment; on the contrary, naltrexone administration reduced the LH response to GnRH in hyperinsulinemic women but failed to be effective in normoinsulinemic subjects. Only 5 patients showed no concordance of drug-induced changes in insulin and LH secretion. In control subjects, naltrexone failed to have any effect on insulin or LH secretion. These data support the involvement of endogenous opioids in the regulation of insulin and LH secretion in a specific group of PCOS patients exhibiting an exaggerated insulin response to OGTT.

Adult↗

PubMed1995

Guidelines for the use of zidovudine in pregnant women with HIV infection.

Zidovudine therapy seems to be effective for reducing vertical transmission of HIV infection and preventing paediatric AIDS. Besides those cases in which it is indicated, zidovudine plays an important role in safeguarding maternal well-being. Even though no data indicating teratogenic effect of this drug exist, its use during the first trimester should be limited to those cases where it is absolutely indicated. All undergoing this therapy should be informed that no information regarding the long term effects of this drug are available yet. Further controlled studies are necessary if this drug is to be used in those cases where it could actually be of benefit.

Female↗

PubMed1995

In vitro human growth hormone increases human chorionic gonadotropin and progesterone secretion by human placenta at term: evidence of a modulatory role by opioids.

We examined the in vitro effect of human growth hormone (hGH) on hormone placental production and the modulation by opioids of this function. Small placental fragments from 12 term placentas were incubated at 37 degrees C in a 95% air and 5% CO2 atmosphere for 4 h with various concentrations of hGH (1-1000 ng/ml) or naloxone (3-500 ng/ml). Both hGH and naloxone increased the concentrations of human chorionic gonadotropin (hCG) and progesterone in the media. The effect of the hGH was dose-dependent and statistically significant at 10 ng/ml, while naloxone was able to increase hCG and progesterone production only at the highest doses (250-500 ng/ml). The concomitant treatment with ineffective doses of naloxone and hGH was able to enhance hCG and progesterone secretion reaching levels similar to those obtained with the highest doses of hGH alone. High naloxone concentrations significantly decreased both hCG and progesterone secretion induced by high doses of hGH. This study confirms the relevance of growth hormone in sustaining placental endocrine activities and indicates an effect of opioids in modulating these functions.

Chorionic Gonadotropin↗

PubMed1995

Effect of corticotropin-releasing factor on the pituitary-ovary axis in human luteal phase.

In order to test the possible negative effect of corticotropin-releasing factor (CRF) on the pituitary-gonadal axis, two gonadotropin-releasing hormone (GnRH) tests, on two consecutive days, were performed in five normally cycling women in the midluteal phase of the menstrual cycle. The first GnRH test was performed after 2 h during which time basal blood samples were collected every 10 min. On the second day, the GnRH test was repeated after a 2-h CRF infusion which was continued throughout the GnRH test. Our results demonstrate that while CRF increases cortisol levels it affects neither the basal nor the GnRH-stimulated gonadotropin levels. Similarly, both basal and luteinizing hormone (LH)-stimulated progesterone concentrations were not modified by the CRF infusion thereby also excluding a possible direct effect of the peptide on corpus luteum steroidogenesis.

Adult↗

PubMed1995

Synthesis and pharmacological properties of thieno[2',3':4,5]pyrimido [2,1-b][1,3,4]thiadiazine derivatives.

A new series of 2-substituted-7,8-dimethyl-3H,9H-thieno[2',3':4,5]pyrimido[2,1- b][1,3,4]thiadiazin-9-ones 5a-d and 6a,b was synthesized through the hydrazinium(1+) salt of 3-amino-2,3-dihydro-5,6-dimethyl-2-thioxo- thieno[2,3-d]pyrimidin-4(1H)-one, 2. These derivatives and two analogs 10a,b were tested for their analgesic and antiinflammatory properties. The pharmacological results are discussed in comparison with those of related compounds previously tested.

Analgesics↗

PubMed1995

Polycystic ovary disease. A risk factor for gestational diabetes?

We investigated the impact of pregestationally elevated insulin plasma levels on glycemic control in pregnant women with polycystic ovary disease (PCOD). Twelve patients with PCOD who became pregnant within six months following evaluation of their metabolic status were the study subjects. Four were obese and six (two obese) had a hyperinsulinemic response to the oral glucose tolerance test (OGTT). They were tested with the OGTT at 28-30 weeks of gestation. We also tested 12 normal patients and 10 consecutive patients with gestational diabetes; all were at the same gestational age. Plasma levels of insulin and glucose were determined in the samples collected for a period of four hours after glucose load (100 g). All PCOD patients significantly increased their insulin secretion in pregnancy. The hyperinsulinemic PCOD patients developed gestational diabetes (two patients) and impaired gestational glucose tolerance (three patients). The area under the insulin curve was greater in PCOD patients than in control and gestational diabetes patients (P < .01). In spite of their large increase in insulin secretion observed during pregnancy, patients with PCOD may develop a derangement of glycemic control, probably related to their pregestational insulinemic status.

Analysis of Variance↗

PubMed1995

Personality, inner experience and compliance in advanced cancer patients treated with external pumps.

The presence of portable pumps for protracted infusional chemotherapy in metastatic solid tumors at an advanced stage determines the need to evaluate psychologically the inner experience of the patients in relation to this therapeutic modality. The objective of the study were to analyze personality variables (coping and awareness), inner experience variables (acceptance and expectations) and the compliance of the patients during repeated courses of therapy. In addition we evaluated the influence of sex, age, level of education and response to treatment in relation to these variables. From February 1992 to March 1994 we evaluated 50 metastatic patients with a psycho-dynamic interview at the 1st, 3rd, 6th and the 9th course of therapy. The data obtained showed a positive trend for all the variables examined and in all the subgroups (age, sex, level of education, response) up to the 6th course. After the 6th course, personality variables remained stable, yet a drop in variables related to inner experience and compliance was observed in the whole group. While the personality variables remain constant in all patients, a decrease of acceptance and expectation was observed in patients non responding to therapy for their tumor, a trend which becomes significative at the 9th course regards expectation. The use of a psycho-dynamic interview allowed us to evaluate the effect of treatment on psychological variables and compliance to therapy. The length of treatment and the response to treatment seem to influence the more profound inner experiences of the patients.

Adaptation, Psychological↗

PubMed1995

Purification of LamB proteins using continuous elution electrophoresis: a comparison with immunoaffinity chromatography.

LamB is a membrane protein that allows the exposition of a foreign peptide on the surface of a recombinant E. coli cells. An immunopurified hybrid LamB protein has been used to elicit high-titre antibodies to a foreign epitope. Looking for a simpler purification procedure we have compared the traditional approach, which includes affinity chromatography, to continuous elution electrophoresis, in the purification of two different hybrid LamB proteins as foreign epitopes. The results obtained showed that both methods yielded the same purification, although the electrophoretic procedure had a higher yield. Continuous-elution electrophoresis could be a useful tool for the purification of membrane proteins.

Antibodies, Monoclonal↗

PubMed1995

Cocaine during pregnancy: a critical review of the literature.

A number of epidemiological indices suggest that the use of cocaine in Italy is increasing, thus explaining the importance of scientific interest in this field. There is considerable disparity between the scientific papers published in the literature concerning the damaging effects on fetus and mother linked to the use of cocaine during pregnancy. The main problem consists of the method used to identify those patients using cocaine. These methods are burdened by a high level of false negatives: subjects who often use a variety of active pharmacological substances are identified and the methods are not always suitable for classifying subjects according to useful clinical parameters. This is reflected in the poor quality of data concerning the epidemiology and clinical aspects of cocaine abuse during pregnancy. A careful selection of the best scientific papers published in the literature shows that the effects on the maternal organism are slight, whereas those on the fetus are more severe. Compared to controls, the use of cocaine is associated with a high percentage of cardiac malformations, preterm delivery, low birth weight and minor anomalies of the nervous system. Results relating to sudden neonatal death are discordant. This paper shows that the use of cocaine is often underestimated both in epidemiological terms and from the fetal point of view. This behaviour is linked to the belief that the effects of cocaine are benign.

Abnormalities, Drug-Induced↗

PubMed1995

Monoclonal antibodies against antigens exposed on the surface of vegetative forms and spores of Myxococcus virescens.

Twelve monoclonal antibodies (mAbs) directed against cell-surface antigens of Myxococcus virescens cells were developed and partially characterized. All of them recognized multiple, diffuse proteic bands in Western blot and four were also reactive to living bacteria, as assessed by flow cytometry. The four latter mAbs recognized antigens common to a number of vegetative forms and spores. The selective expression of proteins recognized by mAbs on the microorganisms and the possible applications of mAbs to the study of myxobacterial cell interaction are discussed.

Antibodies, Bacterial↗

PubMed1995

Synthesis and pharmacological evaluation of thieno[2,3-d]pyrimidin-2,4-dione and 5H-pyrimido [5,4-b]indol-2,4-dione derivatives.

Two series of novel derivatives based on the thienopyrimidine and pyrimidoindole ring systems, both N-substituted in position 3, have been synthesized. The compounds were obtained by reaction of N-amino groups of 5,6-dimethyl-thieno[2,3-d]pyrimidin-2,4-dione and of 5H-pyrimido[5,4-b]indol-2,4-dione with aromatic aldehydes. Some of these substances showed an appreciable analgesic activity, a good antiinflammatory activity, a low acute toxicity with an optimal gastric tolerance.

Analgesics, Non-Narcotic↗