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T Gentile

Publications and source records attributed to T Gentile.

At least 19 recordsLinked to original sources

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↗

IgG asymmetric molecules with antipaternal activity isolated from sera and placenta of pregnant human.

The proportion of symmetric and asymmetric IgG molecules was studied in 10 mothers at delivery. IgG was obtained from peripheral blood and placental blood sera and by elution at 4 M KCl from placenta cell membranes. The percentage of symmetric and asymmetric molecules was determined in the IgG and in their corresponding F(ab')2 fragments by absorption to Con A-Sepharose. The presence of antipaternal antibodies was investigated by IIF and MC tests using paternal lymphocytes. The average percentage of asymetric IgG molecules in the sera was 24.4, which is about double the value of that found in normal subjects. In the IgG eluted from the placenta, the proportion of asymmetric IgG was much higher, averaging 44.4%. Antipaternal antibodies were detected in 5 mothers by IIF and MC and in two mothers only by IIF. In three mothers no antibodies could be detected. It was found that the concentration of antipaternal antibodies was about three times higher in the asymmetric IgG fraction than in the summetric one. Considering the percentage of asymmetric IgG molecules with antipaternal antigen specificity eluted from placenta and the possibility that they function as blocking antibodies, their participation in fetal protection is suggested.

Cytotoxicity Tests, Immunologic↗

[Effect of pre-treatment with pyridostigmine on the stimulation of growth hormone by clonidine and GRF].

The large availability of biosynthetic GH suggested the need to define the more accurate way to make diagnosis of GH deficit. Only one stimulation test by clonidine or insulin is not enough to define a GH deficit, and this because often it's possible to get "false negative" tests. The GH is regulated by the influence of GRF and somatostatin that respectively are under the adrenergic and cholinergic control, for this reason we studied how and in which measure a cholinergic agonist (pyridostigmine) acts on GH release during the clonidine and GRF stimulation tests. We studied the area under the curve (AUC), the peak and the mean of the value of GH after clonidine or clonidine and pyridostigmine, and after GRF or GRF and pyridostigmine: we got the following results: 191 +/- 71.33 (AUC), 5.42 +/- 1.68 (peak), 2.44 +/- 0.54 (mean) after clonidine stimulation test; 1048 +/- 442.37 (AUC), 19.5 +/- 10.15 (peak) and 7.96 +/- 3.2 (mean) after clonidine and pyridostigmine (p less than 0.01); 1499 +/- 887 (AUC), 21.1 +/- 11.8 (peak) and 11.11 +/- 6.6 (mean) after GRF test and 2370 +/- 332 (AUC), 31.4 +/- 3.49 (peak) and 18.22 +/- 3.27 (mean) after GRF and pyridostigmine. The pyridostigmine effect on the simulation by clonidine and GRF is able to potentiate the stimulation of GH and allowed a more accurate diagnosis of GH deficit.

Adolescent↗

Asymmetric Fab glycosylation in guinea-pig IgG1 and IgG2.

The presence of asymmetric antibody molecules has been investigated in both IgG1 and IgG2 subclasses of guinea-pig immunoglobulins. It was found that about 20% of the IgG1 and 10% of the IgG2 were of asymmetric type. The proportion was essentially the same in the sera of normal animals, animals hyperimmunized with dinitrophenyl-bovine gamma globulin (DNP-BGG) and Freund's adjuvant, and animals infected with Trichinella spiralis. In the case of animals immunized with DNP-BGG, no differences were observed in the proportion of asymmetric molecules between the specific antibodies and the IgG not specific for the immunizing antigen. It is concluded that the asymmetric glycosylation occurs to a different extent in each subclass and that it is not affected by the antigen specificity of the antibodies studied.

Animals↗

Asymmetrically glycosylated IgG isolated from non-immune human sera.

When human IgG or its F(ab')2 fragment purified from a pool of non-immune sera was passed through a Con A-Sepharose column, 12% of the molecules bound to concanavalin A. While 44% of Fab' and 72% of Fd' fragments obtained from F(ab')2 retained by concanavalin A and eluted with methyl alpha-D-mannoside bound to concanavalin A, the Fab' and Fd' fragments obtained from non-retained F(ab')2 and the L chains and Fc fragments did not interact with the lectin. Only Fd' fragment obtained from the F(ab')2 retained by concanavalin A inhibited the fixation of guinea-pig erythrocytes to concanavalin A. These results are similar to those previously observed for IgG antibodies of different animal species and indicate that partial asymmetric glycosylation is a general phenomenon that is not restricted exclusively to IgG molecules with known specificity.

Animals↗

Sport and growth.

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Adolescent↗