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Biomedical subjects

R Attanasio

Publications and source records attributed to R Attanasio.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effects of tamoxifen on GH and IGF-I levels in acromegaly.

Tamoxifen (TAM), a non steroid partially competitive antagonist to the estrogen receptors, has been reported to decrease plasma GH and IGF-I levels both in vitro and in vivo. These data prompted us to evaluate GH and IGF-I changes in acromegaly after acute and chronic TAM administration. Nineteen acromegalic patients (6 M, 13 F, aged 30-70 years) were studied in a prospective open study. Acute TAM test (20 mg po) did not induce any significant change in GH and IGF-I levels. Chronic TAM treatment (20 mg/day for a month and 40 mg/day for another month) induced a transient increase in GH levels (from 9 [3-139] micrograms/l [median, range] to 12 [3-188] micrograms/l, p = 0.0025) and a persistent decrease in IGF-I levels (from 785 [500-1200] micrograms/l to 553 [209-1420] micrograms/l, p = 0.0034). Individual IGF-I values decreased in 13 patients and reached the normal range in 4 of them. At TAM withdrawal hormonal levels increased up to pretreatment values. There was no correlation between GH and IGF-I changes and results were not influenced by age, sex or gonadal status. In this setting it is likely that the observed decrease in plasma IGF-I levels is dependent on TAM activity at the hepatic level.

Acromegaly↗
PubMed1997

DNA-based immunization induces anti-CD4 antibodies directed primarily to native epitopes.

DNA-based immunization is one of the most promising strategies to induce protective immunity against a variety of pathogens, presenting clear advantages as compared to the use of recombinant antigens. One of these advantages might be the ability to induce antibodies directed primarily against conformational determinants, as compared to immunization with recombinant proteins. To test this possibility, we have analyzed the antibody responses induced in mice by immunization with either recombinant soluble CD4 (rCD4) or by immunization with plasmid DNA-encoding CD4 (CD4-DNA). Mice immunized with CD4-DNA had lower titers of antibodies able to recognize rCD4 than mice immunized with rCD4. However, immunization with CD4-DNA induced antibodies reactive with the native cell surface CD4 molecule in all mice, whereas only two out of five mice immunized with rCD4 produced antibodies reactive with cell surface CD4, thus demonstrating that the genetic immunization approach may lead to an antibody response more consistent and superior at a qualitative level as compared to immunization with the corresponding recombinant protein. In addition, differences in the kinetics of appearance of antibodies directed against the native CD4 molecule were observed between mice immunized with CD4-DNA or rCD4. In the first case, antibodies reacting with cell surface CD4 were present 28 days after the first immunization, whereas mice immunized with rCD4 produced antibodies directed against the native molecule only following a booster injection. Finally, the two groups of mice produced antibodies with a different isotype distribution. No clear predominance of a specific IgG subclass was detected in the antibody population produced in response to DNA immunization. Conversely, mice immunized with rCD4 produced predominantly antibodies of the IgG1 isotype, indicating generation of a TH2 response. Together, results from this study indicate that the CD4 molecule endogenously produced following DNA immunization is expressed, at least partially, in a native conformation. This feature confers a major advantage to the DNA immunization approach as compared to immunization with the corresponding recombinant protein, which seems to elicit antibodies predominantly directed to epitopes uniquely expressed on the recombinant molecule.

Animals↗
PubMed1997

An overview of bruxism and its management.

Bruxism is a mandibular parafunction and it can be regarded as a forcible clenching or grinding of the dentition or a combination of both. Because bruxist behavior can be exhibited during both waking and sleeping hours, neither aspect should be ignored by the practitioner as a potential contributing factor of disturbances of the masticatory system. This article provides a general overview of bruxism relative to epidemiology, etiology, characteristics, diagnosis, and management.

Bruxism↗
PubMed1997

Intraoral orthotic therapy.

Despite the unanswered questions on the physiologic mechanisms that explain the effectiveness of intraoral orthotics on reducing symptoms of TMD, there is still a plethora of documentation that intraoral orthotics, when appropriately used in the management plan, can contribute to the relief of TMD symptoms. The clinician is encouraged to evaluate fully each particular patient case in an effort to develop a differential diagnosis that leads to an effective management plan, which, in turn, addresses the cause(s) as best as possible. Before commencing any intraoral orthotic therapy for a TMD, the clinician should be confident that the patient will benefit from the therapeutic approach to be employed or, at least, that the resultant effect, or lack thereof, on the symptoms will provide additional diagnostic information. The clinician also needs to take into account that approximately 40% of patients suffering from TMD demonstrate a favorable response to intraoral orthotic therapy just from a placebo effect. As with any treatment, a good patient-dentist relationship concomitant with patient education can allay patient concerns and anxieties, which, in and of themselves, can contribute to a positive and favorable response to intraoral orthotic therapy.

Facial Pain↗
PubMed1996

Effects of terguride on anterior pituitary function in parkinsonian patients treated with L-dopa: a double-blind study versus placebo.

In a randomized double-blind study, 20 parkinsonian patients (suffering from the disease for 2-18 years), chronically treated with levodopa (500-750 mg/day for 0.5-12 years), received terguride (1 mg b.i.d.) or placebo for 4 weeks. Growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), and insulin-like growth factor (IGF-I) secretions were studied before and after the morning dose of levodopa (250 mg p.o.), both before and at the end of study period. At the beginning of the study, basal hormonal levels were within normal limits, and levodopa administration induced a significant suppression in PRL and TSH levels (both p < 0.01)) and a significant increase in GH (p < 0.01). The same results were observed at the end of the study period in the placebo group. Addition of terguride induced a significant suppression in basal PRL levels (p < 0.01), whereas levodopa-induced hormonal changes were unaffected. These data suggest that the hypothalamic dopaminergic function that controls anterior pituitary hormones is preserved in parkinsonian patients, regardless of both the duration of the disease and the long-term treatment with levodopa. The strong additional prolactin-lowering effect of terguride indicates long-lasting dopaminergic effects, as is already known from hyperprolactinemic conditions. The dopaminergic effects of levodopa on TSH, GH, and IGF-I secretion were unchanged by terguride treatment. The anti-dopaminergic effects of terguride observed in the motor system in animal studies, as well as in levodopa-induced dyskinesias in parkinsonian patients, could not be observed in the case of the dopaminergic control of anterior pituitary hormones under the conditions of this study.

Aged↗
PubMed1995

Persistence of somatostatinergic tone in acromegaly.

It is a matter of debate whether hypothalamic somatostatin (SRIH) secretion in acromegaly is preserved and still regulated by the physiological feedback mechanisms of growth hormone (GH) and insulin-like growth factor I. To gather further information on this, the reproducibility of plasma GH changes induced by growth hormone-releasing hormone (GHRH) administration was evaluated in 15 acromegalic patients. There was a highly significant correlation between the peak/basal ratio (P/B) GH response in the 15 patients administered GHRH on two separate occasions (r = 0.99, p < 0.001). The test was performed also before and after the administration of drugs able to inhibit or stimulate hypothalamic SRIH release, by activating (pyridostigmine) or inhibiting (pirenzepine) cholinergic pathways, respectively. The GHRH-induced GH response (P/B = 2, range 1.1-26.1) was increased significantly by pyridostigmine pretreatment in 30 patients (P/B = 2.6, range 1.3-34.8; p = 0.0045). In nine out of 30 patients an increase of greater than 2 SD of within-subject GHRH variability was observed in response to GHRH plus pyridostigmine when compared to GHRH alone. An inverse correlation (r = -0.37, p < 0.05) was observed between GH response to GHRH alone and after pyridostigmine pretreatment. On the contrary, no change of GHRH-induced GH response was observed in 12 patients after pirenzepine pretreatment (P/B = 1.9, range 1.1-5 and P/B = 2, range 1.3-6 without and after pirenzepine pretreatment, respectively). These data suggest that in acromegaly the somatostatinergic tone does not seem to fluctuate, and that it can be inhibited often by cholinergic pathway activation but not increased further by cholinergic suppression.

Acromegaly↗
PubMed1994

Folding patterns of immunoglobulin molecules identified by urea gradient electrophoresis.

The reversible denaturant-induced unfolding of immunoglobulin molecules has been analyzed by transverse urea gradient gel electrophoresis and the effects that urea-induced unfolding exerts on the functional properties associated with their variable region, i.e. antigen binding and idiotypic expression, have been determined by Western blot analysis. Results obtained from these experiments indicate that urea-induced unfolding of the immunoglobulin molecule is a highly cooperative reversible process that occurs through a two-state transition with no accumulation of intermediates. The unfolding transition has its midpoint at about 6.5 M urea and appears to be slow on the time scale of electrophoresis. Folding intermediates in rapid equilibrium with the unfolded state as well as molecular forms with different electrophoretic mobility can be detected during refolding reactions. Results from Western blot analysis confirm the highly cooperative reversible urea-induced unfolding of immunoglobulin molecules and demonstrate that the unfolding transition leads to disappearance of both antigen binding and idiotypic expression, whereas the ability to interact with antibodies directed to continuous epitopes of the variable region is preserved. After progressive removal of the denaturing agent, the variable region refolds into structures that regain the functional properties of the native conformation.

Animals↗
PubMed1993

Anti-peptide reagent identifies a primary-structure-dependent, cross-reactive idiotype expressed on heavy and light chains from a murine monoclonal anti-CD4.

A synthetic peptide corresponding to the second complementarity determining region (CDR2) of the immunoglobulin (Ig) variable (V) region heavy (H) chain (CDR2VH) of anti-Leu3a, a murine monoclonal antibody specific for the human CD4 molecule, was used to elicit the production of specific rabbit anti-peptide antibodies. The rabbit anti-peptide antiserum was tested for reactivity against the immunizing peptide, anti-Leu3a, and a panel of mouse monoclonal anti-CD4. Only the immunizing peptide and anti-Leu3a were recognized by ELISA, whereas the H chains of anti-Leu3a and five other monoclonal anti-CD4 preparations were recognized by Western blot analysis. These data suggest that linear structures corresponding to the CDR2VH are not normally exposed on the surface of these monoclonal antibodies and become accessible only upon unfolding of the Ig molecule. In addition, Western blot analysis demonstrated that the anti-CDR2VH peptide antiserum was able to recognize the Ig light (L) chain of anti-Leu3a. This reactivity to both H and L chains from anti-Leu3a was ascribed to a homologous five amino acid sequence region shared by the two chains. The region of homology was associated with the third framework (FR3) of the L chain and was included as a portion of the sequence in the CDR2VH synthetic peptide. This observation was confirmed by the ability of the CDR2VH anti-peptide antiserum to bind the L chains of three mouse myeloma proteins that exhibited the five amino acid sequence region of homology within their respective FR3. Together, these data provide information on the structural basis of idiotypes shared by the H and L chains from the same antibody molecule and indicate that five amino acids might be sufficient to define a minimal continuous idiotypic determinant.

Amino Acid Sequence↗
PubMed1993

Memory impairment in Cushing's disease.

In the present study the cognitive performance of 25 patients with Cushing's disease (CD) was extensively evaluated in comparison with normal control subjects, matched one by one. The results indicate a selective impairment of memory functions: the number of patients showing a significantly impaired mnesic performance increases with age. Moreover, the neuropsychological impairment tends to recover in those cases who underwent further controls after surgical treatment. The neuropsychological data are discussed in the light of recent evidence in the literature concerning the effects of adrenal steroids on the brain.

Adolescent↗
PubMed1993

CV 205-502 in acromegaly.

In a series of acromegalic patients the effects of CV 205-502, a new long-acting dopamine-agonist drug, on growth hormone (GH), insulin-like growth factor I (IGF-I) and prolactin (PRL) levels were evaluated in an open study. After acute administration of CV 205-502 (0.0375 mg, po) in 12 patients. GH levels did not change, whereas PRL values significantly decreased and remained suppressed for 24 h. In the 14 patients who underwent chronic CV 205-502 treatment (at daily doses of 0.150-0.600 mg/day given at bedtime or b.i.d. for up to 12 months). GH and IGF-I levels fell significantly from 60 +/- 17 (mean +/- SEM) micrograms/l to 28 +/- 10 micrograms/l and from 1127 +/- 84 micrograms/l to 738 +/- 57 micrograms/l, respectively (p < 0.05). A retrospective comparison with the results obtained for the same patients during a previous chronic bromocriptine treatment (at daily doses of 5-20 mg given t.i.d. or q.i.d.) did not show any significant difference in the suppression of GH levels between the two treatments; no bromocriptine-resistant patient was CV 205-502 sensitive, even at the highest CV 205-502 dose used. We conclude that in acromegaly chronic treatment with this new dopaminergic drug has a GH- and PRL-lowering effect that is similar to but more prolonged than that of bromocriptine, and normal or near-normal GH and IGF-I levels may be obtained in a few patients with b.i.d. administration. However, no GH-lowering effect is observed in bromocriptine-resistant patients.

Acromegaly↗
PubMed1992

Characteristics of murine monoclonal anti-CD4. Epitope recognition, idiotype expression, and variable region gene sequence.

We have characterized a series of mouse monoclonal anti-CD4 and describe both their CD4 epitope recognition and Id expression. We also determined the V region gene sequences of these antibodies in an attempt to correlate epitope recognition and Id expression with V region sequence. All of these preparations recognize epitopes that cluster around the HIV gp120 binding site on the human CD4 molecule. However, we observed differences in epitope recognition among the anti-CD4 preparations, based on either competitive inhibition assays or functional assays, such as syncytium inhibition. Analysis of Id specificities using a polyclonal anti-Id generated against anti-Leu 3a indicated that five of the seven monoclonal anti-CD4 expressed a shared Id. Based on V region gene sequences, the V region kappa-chain (V[kappa]) from each of the seven antibodies was encoded by the V[kappa]21 gene family and expressed the J[kappa]4 gene segment. Those preparations that expressed the shared Id with anti-Leu 3a have virtually identical V[kappa] sequences, with a high degree of homology in the CDR. The VH region gene sequences of six of the seven antibodies also shared overall homology and appeared to be encoded by the J558 VH gene family. The seventh anti-CD4 VH region is encoded for by the VHGAM gene family. The majority of these antibodies used JH3 gene segment, although the JH2 and JH4 gene segments were also represented. In addition, several of these antibodies share a common sequence organization within their V-D-J joining regions that appears to involve N and P sequences to generate unique D segments. Together, these data suggest that differences in epitope recognition among the monoclonal anti-CD4 may reflect sequence variability primarily within the CDR3 region of both V[kappa] and VH. The basis for the detection of a shared Id most likely reflects the high degree of homology within the V[kappa] region sequences. In addition, these data, which are based on a limited analysis, suggest the possible restricted use of V region germ-line gene families in the secondary antibody response of BALB/c mice to specific epitopes on the human CD4 molecule.

Amino Acid Sequence↗
PubMed1992

A preliminary diagnostic and treatment protocol.

The objectives of the preliminary diagnostic and treatment protocol are 1. To reveal retention or resistance form deficiencies. 2. To reveal need for augmentive periodontal crown-lengthening surgical procedures. 3. To evaluate pontic form for the existing space. 4. To preplan occlusal plane deficiencies and methods of corrective treatment to establish Curve of Spee. 5. To preplan occlusal scheme, i.e., canine guidance, group function, mutually protected occlusion, and cross-bite conditions. 6. To aid in preplanning sequence of treatment and method of preservation of occlusal vertical dimension. 7. To serve as a visual aid for discussion of treatment recommendations with patient prior to actual treatment. 8. To act as a medicolegal record to document the clinician's pretreatment planning in complex treatment situations for possible use in peer review or litigation. 9. To aid in fabrication of an elastomer reduction guide for use during crown preparation. 10. To aid in fabrication of a vacuum-formed template for provisional restoration of crown and abutment teeth after preparation.

Clinical Protocols↗
PubMed1992

Clinical decision analysis in fixed prosthodontics.

Structured clinical decision analysis in dentistry in fixed prosthodontics, as in any branch of dentistry, allows the practitioner to think through more clearly the problems at hand based on the clinical data and extenuating factors presented by the patient. This discipline of decision making is intended to complement the experience level and educational background of the clinician in assisting him or her through the decision process. Additionally, CDA helps the clinician define not only the pre-existing condition of the patient prior to irreversible therapy, but also which treatment strategies may best be suited for that individual over an extended period. The systematic nature of decision analysis stimulates the focusing of one's attention on those factors considered to be germane to the overall complexity of the case and, at the same time, excluding those factors having little or no influence on its final outcome. With further implementation of computerized databases and procedural outcome probabilities based on clinical and laboratory studies as well as the clinical experience of those choosing to use it, the future for structured, formalized clinical decision analysis seems quite promising.

Decision Support Techniques↗