Search PubMed⌕ Search

Biomedical subjects

T Gentile

Publications and source records attributed to T Gentile.

At least 19 recordsLinked to original sources

Imaging of the patient with chronic bronchitis: an overview of old and new signs.

Up to now, neither chest radiograph nor high-resolution computed tomography (HRCT) has much to offer to the diagnosis of patients with chronic bronchitis (CB). A lot of HRCT findings can be observed, but they cannot be regarded as specific for pure CB. Their evaluation is often subjective, and measurements are poorly reproducible. In order to better characterise the HRCT features of CB, further efforts are warranted. The finding of bronchial wall thickening may even be considered nonsensitive as well as nonspecific. CB should not only be equated with narrowing of the airway since thickness of the bronchial wall may vary among different stages of development. Small pits can often be detected along the inner surfaces of the large bronchi in patients with CB using volumetric thin-section CT. Sometimes, multiple pits give rise to the accordion-like appearance that was described using bronchography. In our experience, they often occur in patients with long-lasting CB. A better comprehension of the large airways abnormalities is important because it is likely that the same pathophysiologic process that causes small-airway obstruction also takes place in larger airways, where it has less functional effect.

Bronchitis, Chronic↗

Reliability and validity of a patient self-administered daily questionnaire to assess impact of oral mucositis (OM) on pain and daily functioning in patients undergoing autologous hematopoietic stem cell transplantation (HSCT).

Oral mucositis (OM) is a frequent complication of myeloablative therapy and HSCT. We evaluated the feasibility, reliability, and validity of a new patient self-reported daily questionnaire on OM and its impact on daily functions. This OM Daily Questionnaire (OMDQ), containing 10 items, was developed for use in palifermin clinical trials. In a phase 3 study, 212 patients received palifermin or placebo for three consecutive days before conditioning and three consecutive days after HSCT. Compliance rates were consistently >80% for most patients. Mouth and throat soreness (MTS) and MTS-Activity Limitations (MTS-AL) (swallowing, drinking, eating, talking, and sleeping) scores on consecutive days were highly correlated (days 7,8 = 0.70-0.86; test-retest reliability). Correlations among items measuring the same construct ranged between 0.5 and 0.8 (internal consistency reliability). The WHO Oral Toxicity scale was the clinical comparator to assess the criterion, discriminative, and evaluative validities of MTS-related questions. Most correlation coefficients between the WHO and MTS ranged between 0.45 and 0.55. Patients with more severe WHO OM grades had higher MTS mean scores. Changes in MTS scores were similar, but patients detected changes 1-3 days earlier than clinicians. In conclusion, the OMDQ is a feasible, reliable, valid, and responsive patient-reported measure of OM severity.

Activities of Daily Living↗

Interleukin-6 and dexamethasone modulate in vitro asymmetric antibody synthesis and UDP-Glc glycoprotein glycosyltransferase activity.

The increased production of asymmetric IgG protective antibodies is one of the mechanisms proposed to explain a successful semiallogeneic pregnancy. We have previously demonstrated that IL-6 was able to enhance the synthesis of these antibodies by a murine hybridoma, while the glucocorticoid dexamethasone (DEXA) diminished it. In order to investigate the mechanism of asymmetric antibody synthesis, we investigate the role of UDP-Glc glycoprotein glucosyltransferase (GT), an endoplasmic reticulum enzyme involved in the quality control and folding of glycoproteins. Either recombinant murine rmIL-6 (0-10-40-160-320-640 ng/ml) or DEXA (0.15 microM) were added to a mouse hybridoma culture and incubated for 24 and 72 h in the first case, and for 4h in the presence of DEXA. Anti-DNP asymmetric antibodies were determined in the culture supernatants by ELISA. After harvesting, hybridoma cells were sonicated and GT activity was analysed in isolated microsomal fractions by measuring UDP((14)C)-Glc incorporation into urea-denatured thyroglobulin (urea-Tg). In the present paper, we showed that IL-6, mainly at 40 ng/ml and t=24h, was able to upregulate both in vitro GT activity (+74%) and asymmetric molecule synthesis (+227%). Lower increases were obtained employing 10 and 160 ng/ml. On the other hand, DEXA, at 0.15 microM and t=4h, showed a mild inhibition of enzyme activity (-10%) and a diminished proportion of asymmetric IgG (-49%). A direct relationship between GT activity and proportion of the asymmetric antibody synthesised was found in our hybridoma cells employing IL-6 and DEXA in different conditions, as was indicated by a correlation analysis. These results suggest that GT might be involved in the synthesis of asymmetric antibodies.

Animals↗

In vitro and in vivo effects of progesterone on Trichinella spiralis newborn larvae.

We have previously demonstrated that during pregnancy there exists an increased parasiticide activity against Trichinella spiralis newborn larvae (NBL) in infected rats. In this work we analysed the contribution of peritoneal cells from noninfected pregnant rats to the mortality of the NBL in cytotoxicity assays, and evaluated the role of progesterone in this effector mechanism. Our findings suggest that progesterone can induce activation of effector peritoneal cells to destroy the NBL in a rapid and antibody-independent manner. The administration of progesterone to ovariectomized rats also led to a significant decrease in the parasite load of the animals, thus demonstrating that progesterone induces the increase of the parasiticide activity of the leukocytes involved in the mechanisms of NBL death.

Animals↗

Asymmetric antibodies: a protective arm in pregnancy.

In normal conditions, a simple change in the pattern of cytokines towards a Th2 response is associated with the production of aggressive antibodies. This fact could not completely explain phenomena such as the fetal survival or the chronicity of certain infections. However, it has been demonstrated that Th2 cytokines increase the proportion of asymmetric antibodies, which are unable to activate effector immune mechanisms (complement fixation, clearance of antigens and phagocytosis). Investigations of asymmetrically glycosylated antibodies demonstrated that these IgG molecules have an extracarbohydrate in one of the Fab regions. This glycosylation affects their antigen interaction turning them into a functionally univalent and blocking antibodies. It has been established that their synthesis is increased under different physiopathological situations involving Th2 responses: chronic infections by extracellular microorganisms, pregnancy and allergic processes. In this review we summarize the experiments performed by our research group over the last years as well as the advances made concerning the role and mechanism of asymmetric antibodies.

Animals↗

Regulation of interleukin-6 fetoplacental levels could be involved in the protective effect of low-molecular weight heparin treatment on murine spontaneous abortion.

PROBLEM: CBA/J x DBA/2 abortion rate could be the consequence of a deficient local production of T helper (Th2) cytokines, which cause fetal wastage via fgl2 prothrombinase. Heparin reduces significantly the abortion rate in mice and recurrent spontaneous abortion (RSA) patients. We proposed to determine the effect of enoxaparin on the levels of local interleukin (IL)-6 during murine pregnancy. METHOD OF STUDY: Recombinant human IL-6 (rhIL-6) or enoxaparin were inoculated in CBA/J x DBA/2 pregnant mice on days 6.5-12.5. IL-6 levels in sera as well as in culture supernatants of day 9.5 fetoplacental units of CBA/J x BALB/c control mice or CBA/J x DBA/2 abortion combination were determined by enzyme-linked immunosorbent assay (ELISA) test. RESULTS: CBA/J x DBA/2 fetoplacental units secreted significantly lower levels of IL-6 with regard to CBA/J x BALB/c normal units. rhIL-6h and enoxaparin treatments decreased the resorption rate and regulated IL-6 fetoplacental levels. CONCLUSION: This study suggests that regulation of IL-6 fetoplacental levels could be involved in heparin-mediated anticoagulation protection against abortion.

Abortion, Spontaneous↗

Increased parasiticide activity against Trichinella spiralis newborn larvae during pregnancy.

To evaluate whether pregnancy has a synergetic effect on the host's immune response against Trichinella spiralis infection, immunological and parasitological parameters relating to the infection were assessed in pregnant rats and compared to those observed in virgin infected rats. The muscle parasite load was lower in pregnant infected rats but no differences were found in the intestinal worm burdens or the fecundity of female worms. The ability of sera to mediate death in newborn larvae (NBL) in an antibody-dependent cell cytotoxicity assay was higher for pregnant rats, even in the absence of specific anti-NBL antibodies. High levels of total and anti-NBL IgE were found in both groups, however, these levels were higher in the group of pregnant infected animals. No differences were found in anti-NBL IgGAM titers, nevertheless in some pregnant infected rats these antibodies were found earlier. No differences were found in peritoneal or blood eosinophil counts. Offspring born to infected dams were found to be infected. The results obtained in this model demonstrate that during pregnancy there is an enhanced helminthotoxic effect towards the NBL. Despite this immunoactivation, vertical transmission of the parasite is possible.

Animals↗

Interleukin regulation of asymmetric antibody synthesized by isolated placental B cells.

PROBLEM: Protecting antibodies against trophoblast surface molecules were previously described. Here we analysed the synthesis of asymmetric IgG by placental B-lymphocytes. METHOD OF STUDY: B cells were isolated from human term placenta and cord blood, stimulated with anti-CD40 IgG and cocultured with transfected Fcgamma R-expressing mice Ltk-fibroblast. Interleukin-4, IL-6, IL-10, IL-11 and IL-13 were added to cultures for 14 days. Asymmetric IgG were assessed in culture supernatants by concanavalin A (Con A) fixation and enzyme-linked immunosorbent assay. RESULTS: When IL-6 was added to the cultures, the percentages of asymmetric IgG synthesized by placental B cells were: IL-6: 29 +/- 10; IL-6 + IL-10: 24 +/- 7; IL-4 + IL-10 + IL-6: 38 +/- 9. The last combination induced the highest increase in the asymmetric IgG synthesis as compared with control (19 +/- 10%, P < 0.05). Additionally, placental B cells synthesized more asymmetric IgG than umbilical cord blood B-lymphocytes (P = 0.0015). CONCLUSIONS: Isolated placental B-lymphocytes synthesized asymmetric IgG in response to Th2 interleukins, more notably IL-6 in combination with IL-4 and IL-10. The in vitro increase of protective asymmetric IgG synthesis in response to Th2-cytokines support the hypothesis that a local Th2-switch is beneficial for pregnancy outcome.

Animals↗

Enhancement of in vitro hsp72 expression by placental IL-6.

PROBLEM: To give an approach in order to elucidate the mechanism by which placental IL-6 induce modifications in the glycosylation status of immunoglobulins, in the present work, we investigate a putative relationship between a stimulus by placental IL-6 and expression of cytoplasmic "hsp70 family proteins" in an in vitro model. METHODS OF STUDY: Supernatants of cultures of placentae obtained from primiparous and multiparous AKR/J x AKR/J and AKR/J x BALB/c mouse crossbreedings were added to mouse IgGI hybridoma cultures which produced symmetric and asymmetric anti-dinitrophenol (anti-DNP) antibodies. Analyses of the expression of inducible hsp72/constitutive hsp73 in cellular lysates obtained from hybridomas cultured, in the presence of rmIL-6 or crude murine placental culture supernatants, followed by neutralization assays with anti IL-6, were performed. In addition, the level of IL-6 present in the employed placental culture supernatants was determined and compared with the placental hsp70-inducing effect. RESULTS: These experiments showed that mouse placentae were able to release IL-6 in vitro. In addition, mouse placental supernatants (PS) containing over 1,000 pg/mL of IL-6 enhanced the expression of the inducible isoform hsp72 in the employed hybridomas. This effect was abolished when the hsp70-inducing PS were previously incubated with anti-mIL6 antibody. CONCLUSIONS: These observations indicate that mouse placentae produce different titers of IL-6 and suggest that IL-6 appears to be the unique mouse placental factor able to induce in vitro hsp72 synthesis. A relationship with the increased synthesis of anti-paternal antigen asymmetric antibodies, previously observed during pregnancy, is discussed.

Animals↗

Asymmetric antibodies and pregnancy.

PROBLEM: Asymmetric IgG antibodies (AAb) possess a mannose-rich oligosaccharide residue bound to one of the Fab regions, making them unable to activate immunoeffector mechanisms. The proportion of asymmetric antibodies is increased after prolonged immunization with particulate antigens like cellular spleen cells. During pregnancy, AAb were found in serum and bound to placenta with specific activity to paternal antigens. No previous reports about the status of AAb in recurrent spontaneous abortion (RSA) patients have been published to date. Therefore, the aim of the present study was to analyze the percentage of asymmetric IgG molecules in serum samples of (a) healthy pregnant and non-pregnant women, (b) pregnant women with a history of RSA, and (c) non-pregnant RSA patients receiving paternal lymphocyte immunotherapy (LIT) or intravenous gammaglobulin therapy (IVIgs). METHOD OF STUDY: A previously-described differential ELISA technique was used to determine the percentage of IgG that was of the asymmetric type. RESULTS: During normal pregnancy, there was an increase in the percentage of high ConA affinity IgG serum molecules with a major increase at the second trimester. Pregnant RSA patients at the second trimester had lower values. When evaluating non-pregnant RSA patients who received LIT, it was observed that the immunized patients expressed a higher percentage of asymmetric IgG antibodies. The pregnant patients who received IVIgs had a percentage of AAbs comparable to normal pregnant patients. Additionally, the presence of IgG asymmetric molecules was confirmed in commercial gammaglobulin preparations. CONCLUSION: Results suggest a protective role of AAb during pregnancy.

Abortion, Habitual↗

Improved continuity of care in a community teaching hospital model.

HYPOTHESIS: We created an ambulatory resident clinic in a community teaching hospital to improve the continuity of care in a surgery residency program. DESIGN: A retrospective chart review analysis. SETTING: A community hospital, general surgery residency training program, and its ambulatory practice. INTERVENTIONS: Providence Hospital, Southfield, Mich, has established a new model, the Surgical Associates of Michigan, which is an association comprising private practice physicians serving as full-time faculty in the Department of Surgery. In addition to clarification of teaching requirements and reimbursement for educational activities, the most dramatic feature is the relocation of private practice offices and the staff surgical office to one central location within the hospital. The proximity of the staff and private surgical offices facilitates closer interaction of attending physicians, residents, and patients. MAIN OUTCOME MEASURES: Compliance rates of continuity of patient care provided by the same resident, as presented by the Surgery Residency Review Committee, including confirmation of diagnosis, provision of preoperative care, discussion with attending physician, selection and provision of intervention, direction of postoperative care, and postdischarge follow-up. RESULTS: Since the inception of this arrangement at our institution, surgical residents have seen 229 staff patients and 465 private patients in the offices under supervision. Compliance rate of continuity of care was defined as patient follow-up with the same senior surgical resident who performed an operation or evaluated the patient on initial presentation to the emergency department or offices. We achieved a compliance rate of 92.8% (169/182) in the staff surgical clinics. A compliance rate of 63.5% (205/323) for private general surgical patients and 70.4% (100/142) for vascular surgical patients was obtained. With the establishment of the teaching faculty group and the relocation of offices, we were able to achieve a dramatic improvement in continuity of care. CONCLUSIONS: In addition to fulfilling the Surgery Residency Review Committee requirements, we believe our model facilitates broader education of surgical residents and improves risk management. We recommend further similar studies, greater involvement of primary care specialties in recruiting staff surgical referrals, and implementation of a specialized computer program to continue to improve continuity of care in surgery residency programs.

Continuity of Patient Care↗

Effect of pregnancy and placental factors on the quality of humoral immune response.

Asymmetrical IgG molecules are characterised by the presence of a mannose-rich oligosaccharide group in only one of the two Fab fragments, which impairs the corresponding paratope, causing such molecules to behave as univalent antibodies and therefore as antigen blockers [1-3]. During human and murine pregnancy, an increase has been detected in asymmetrical IgG molecules in serum and those bound to the placenta, which normally releases factors capable of modulating the immune response. It thus seemed of interest to investigate the effect of placental culture supernatants (PCS) on in vivo and in vitro synthesis of rat immunoglobulin IgG1, IgG2a, IgG2b and IgG2C, particularly the ratio of symmetrical and asymmetrical molecules in each isotype. The effect of PCS was determined in vivo by means of passive transfer to virgin females and in vitro by analysing the supernatants of spleen cells cultured in the presence of PCS. The results showed that neither pregnancy status nor PCS were capable of modifying serum levels of IgG2a, IgG2b or IgG2c, whereas the level of IgG1 was reduced. When PCS were added to the spleen cells cultures, an in vitro increase was observed in IgG2a, IgG2b and IgG2c production. The separation of symmetrical from asymmetrical IgG molecules was performed by affinity chromatography in Concanavalin A-Sepharose, as such lectin binds high mannose sugars present only in asymmetrical IgG molecules. It is shown that pregnancy and PCS induce an increase in IgG1 and IgG2 molecules asymmetrically glycosylated, capable of binding to ConA-Sepharose. Therefore, the placenta is capable of releasing factors which can regulate the relative proportion of asymmetrical IgG molecules and induce quantitative and qualitative modifications of the in vitro and in vivo produced antibodies.

Animals↗

Incidence of rat-soluble placental factors on IgE and IgG2a synthesis.

PROBLEM: The in vivo effect of soluble factors present in placental culture supernatants (PCSs) on the synthesis of rat immunoglobulin E (IgE) and IgG2a isotypes was investigated. METHOD OF STUDY: Batches of Wistar SPF rats immunized with a 10-microgram dose of ovalbumin and Al(OH)3 were used: group I, consisted of virgin rats; group II, virgin females injected simultaneously with PCSs; and group III, pregnant females. As controls, nonimmunized batches were included. Serum samples were collected at days 0 (basal) and 10 after antigen challenge, determining levels of total and specific antiovalbumin of both IgE and IgG2a by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: In vivo and at least at the doses administered, PCSs exert an inhibitory effect on the synthesis of specific and total anti-ovalbumin IgE during the course of immune response to such challenge. However, PCSs did not modify serum values of total and specific IgG2a. CONCLUSIONS: These results suggest that PCSs exert selective influence on the synthesis of diverse immunoglobulin isotypes during immune response, through the balance of cytokines synthesized by placental cells.

Animals↗

IgG asymmetric anti-ovalbumin antibodies synthesized by virgin and pregnant rats.

A study on the synthesis of asymmetrical IgG molecules 'with no specific activity' and with anti-ovalbumin activity was carried out both in virgin rats and in rats inoculated with ovalbumin and made pregnant by syngeneic and allogeneic males. Before pregnancy, female rats synthesize about 23% of asymmetrical IgG molecules, when the level of these molecules is assessed in total IgG, in anti-ovalbumin IgG and in the supernatant from the adsorption of anti-ovalbumin antibodies. On the other hand, anti-ovalbumin antibodies isolated are predominantly of the symmetrical IgG type; they are also precipitants and effectors of the biological mechanisms that the host operates to preserve pathogenic antigens (bacteria, parasites). In rats pregnant by syngeneic and allogeneic males, the ratio asymmetric/symmetric IgG molecules increases, and the anti-ovalbumin antibodies are mainly of the asymmetrical IgG type, which aid antigen-blocking. Similar results are found in virgin rats, immunized with ovalbumin and intraperitoneally transferred simultaneously with supernatants of placental cultures. These results suggest that, during pregnancy, there is an increase of the IgG asymmetric/symmetric molecule ratio, produced by placental factors, whatever the immunogen specificity may be. Speculations about this fact are presented.

Animals↗

Growth charts, growth velocity and bone development in childhood obesity.

OBJECTIVE: To compare the growth charts of obese subjects (4-18 years) with the Tanner's growth curves and to analyze the growth velocities and bone age of obese children in prepuberty and adolescence. Moreover to compare the relationship between the serum insulinemic and glycemic levels and height standard deviation score (HSDS). DESIGN: Growth charts: this study included 1250 obese subjects (669 males, 581 females) observed between 1981 and 1993 and divided into seven age categories (4-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18 years). Growth velocities: yearly growth velocities of 579 obese subjects (325 males, 254 females) were compared to growth velocities of 473 controlled children of the same sex, chronological age and pubertal stage. Bone age (BA) of 846 obese subjects (470 males, 376 females) was estimated. Blood analysis: insulin secretion of 70 obese children was considered and compared to 70 lean controls of equal chronological age and sex. MEASUREMENTS: Growth rate, standardized height and other physical characteristics of the children were measured by trained examiners. All subjects were evaluated singularly for at least 4 years with a follow-up every 6 months. BA was estimated by radiograph of the left hand and wrist using the Tanner-Whitehouse II system by a single observer. For the insulin secretion study and glycemic levels oral glucose tolerance test (OGTT) was performed using a glucose load of 1.75 g/kg per body weight. Plasma insulin was assessed by a double antibody radioimmunoassay. RESULTS: In adipose children the growth charts, referred to 97th centile, 50th centile and 3rd centile, were superior to those of the normal population up to the age of 13 and 12.5 years for male and for female respectively; growth decreases at the above age in both sexes. The obese subjects were equal in height to the non obese subjects as they reached their 18th birthday. The growth velocity (cm/yr) of the obese child, in the age range considered here, does not show differences when compared with the lean child in the prepubertal status (P not significant) but decreases during Tanner's stage II, III IV in boys and girls (P < 0.0001). BA is more advanced over chronological age (delta BA-CA) in both sexes. The increase of BA over CA does not show a remarkable difference during pubertal maturation in boys (P not significant); whereas in girls the delta BA-CA decreases with advancing sexual maturation (P < 0.0001). Our obese subjects have significantly higher plasma insulinemic levels compared with the lean controls (P < 0.0001). Moreover there is a positive correlation between plasma insulinemic levels and HSDS (r = 0.881, P < 0.0001). We did not observe a correlation between serum glycemic levels and HSDS. CONCLUSION: Our data demonstrate that the growth increase in an obese child starts in the first years of life. The statural advantage acquired in the first years of life would be exploited and maintained up to the beginning of puberty and with a growth velocity equal to that of the lean subject. Skeletal maturation is strongly increased in both sexes. Bone age remained advanced during the entire period of pubertal development. During puberty obese subjects demonstrate a less notable growth spurt when compared with lean subjects. The growth advantage gradually decreases and final adult height of obese and normal subjects is equal.

Adolescent↗

Partial monosomy of 7q32 in a case of de novo rcp(7;15)(q32;q15).

A de novo apparently balanced translocation between chromosomes 7 and 15 with breakpoints in q32 and q15 respectively is reported in a female child. Clinical features included general growth and psychomotor retardation, feeding problems, microcephaly, low set ears, a short neck, and brachydactyly. These findings suggested possible physical or functional partial monosomy of the 7q32 or 15q15 segments. The phenotype of this case is similar to other cases of 7q deletion.

Abnormalities, Multiple↗

Preferential synthesis of asymmetric antibodies in rats immunized with paternal particulate antigens. Effect on pregnancy.

The effect of immunization of female Fischer rats with particulate (spleen cells) (group I) or soluble (supernatant of disintegrated spleen cells) (group II) paternal antigens previous to mating with Buffalo rats was investigated. The percentage of asymmetric IgG molecules in the serum of rats inoculated with particulate antigens was 38% while in those injected with soluble antigens it was 29% and 28% in non-immunized animals. These percentages further increased during pregnancy to 45%, 38% and 37%, respectively. The antipaternal antibody titres, as determined by indirect immunofluorescence (IIF), was much higher in the animals immunized with particulate antigens but the effector activity, judged by complement fixation, was similar in both groups. The same values were observed at the time of mating (after 3 months of immunization) and at day 17 of pregnancy. Fetus and placenta weights and offspring survival were equally greater in group I than in group II or non-immunized rats (group III). The results obtained indicate the preferential synthesis of antipaternal IgG asymmetric antibodies in rats injected with particulate antigens previous to mating and suggests a beneficial effect of these antibodies in pregnancy.

Animals↗