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Biomedical subjects

R Attanasio

Publications and source records attributed to R Attanasio.

At least 55 records · Page 3Linked to original sources

Structural characterization of a cross-reactive idiotype shared by monoclonal antibodies specific for the human CD4 molecule.

A panel of mouse monoclonal anti-CD4 antibodies was characterized in terms of idiotypic expression by using specific anti-idiotypic antibody (anti-Id) reagents generated in rabbits immunized with anti-Leu3a, a monoclonal anti-CD4 which inhibits the human immunodeficiency virus (HIV) gp120 binding to CD4. Direct binding and competitive inhibition assays demonstrate that the majority of monoclonal anti-CD4 antibodies able to recognize CD4 epitopes overlapping the epitope recognized by anti-Leu3a expressed an antigen-combining site-related cross-reactive idiotype (IdX). Western blot analysis was used to demonstrate that this IdX is associated primarily with the light (L) chain of the monoclonal anti-CD4 antibodies. To further characterize the structural basis of the IdX, the nucleotide sequence of the variable region of the L kappa chain of anti-Leu3a was determined. Peptides corresponding to the first, second, and third complementarity determining regions (CDRs) of the L chain of anti-Leu3a were synthesized and used to immunize rabbits. All anti-peptide antisera recognized the immunizing peptide, the cognate anti-Leu3a molecule, and several other monoclonal anti-CD4 antibodies by direct binding assays. Western blot analysis utilizing the anti-CDR peptide reagents demonstrates that the reactivity to the monoclonal anti-CD4 antibodies was L chain-specific. The anti-Id generated by immunizing with the intact anti-Leu3a molecule failed to recognize the three L chain-derived CDR synthetic peptides, suggesting that the IdX requires the presence of the three-dimensional configuration of the L chain for its expression. The broad range of reactivity exhibited by the antipeptide antisera indicates that the majority of mouse monoclonal anti-CD4 antibodies characterized in this study utilize L chains encoded by a single germ line variable (V) region kappa (V kappa) chain gene or by V kappa genes that belong to the same gene family.

Amino Acid Sequence↗

Anti-idiotypic antibody response to monoclonal anti-CD4 preparations in nonhuman primate species.

A series of mouse monoclonal anti-CD4 preparations was characterized for the ability to recognize overlapping epitopes on CD4 and to inhibit HIV/simian immunodeficiency virus (SIV) syncytium formation. Based on this characterization, mAb able to recognize CD4 epitopes overlapping the HIV binding site were selected and used to immunize nonhuman primates to elicit the production of specific anti-Id antibodies. Five baboons and five rhesus monkeys were immunized with either individual or a cocktail consisting of several monoclonal anti-CD4 preparations. All the nonhuman primates produced specific anti-Id that recognized either private or cross-reactive Id depending on the monoclonal anti-CD4 used to generate the anti-Id response. Inhibition assays were performed to ascertain the ability of: 1) soluble CD4 to inhibit the Id-anti-Id reaction and 2) the various anti-Id to inhibit the CD4-monoclonal anti-CD4 reaction. These studies demonstrated that some of the anti-Id recognized a cross-reactive Id that was associated with the Ag-combining site. In addition, some of the anti-Id weakly recognized SIV gp120 by Western blot analysis. These studies may be useful in designing experiments that may lead to a better understanding of the CD4-HIV gp120 interaction and to the production of Id and/or anti-Id reagents that might be used to manipulate this virus-receptor interaction.

Animals↗

Doxorubicin for acromegaly: a case report.

We report the case of an acromegalic woman, aged 35 years, with a huge GH-secreting tumor, repeatedly treated with neurosurgery and radiotherapy, not responsive to bromocriptine (Br) and octreotide (SMS), whose clinical picture evolved to coma due to endocranic hypertension. Since remnant size was too large to be further treated by surgery, chemotherapy with doxorubicin (DOX) (100 mg i.v. every three weeks up to 0.5 mg/m2 over 7 months) was started. Treatment was followed by a rapid improvement of clinical picture with resumption out of coma, progressive decline of GH levels (from 800 ng/ml to 15 ng/ml) and a slight shrinkage of tumor. No side effects were observed during DOX administration. We suggest that in those few acromegalic patients resistant both to SMS and Br, and with poor prognosis, DOX may be effectively used.

Acromegaly↗

A procedure for making a bruxism device in the office.

Microtrauma to the temporomandibular joint, the masticatory muscles, and the dentition can be significant in mandibular parafunctional activity such as nocturnal clenching and bruxing. Intraoral therapy can be useful in helping to reduce the deleterious effects of this activity. This article presents an in-office procedure for a device to reduce a delay in starting treatment and the time needed for adjustment of the device in the mouth.

Bruxism↗

Immunogenicity of hepatitis B surface antigen derived from the baculovirus expression vector system: a mouse potency study.

A standard mouse potency test was performed to evaluate the immunogenicity of recombinant hepatitis B surface antigen (HBsAg) produced in the baculovirus/insect cell expression system. Groups of NIH Swiss mice were immunized with serial four-fold amounts of either baculovirus-derived HBsAg adsorbed to aluminum sulfate or a commercially available yeast-derived recombinant HBsAg vaccine preparation. Results from these experiments showed that the effective dose of baculovirus- and yeast-derived HBsAg vaccine preparations necessary to seroconvert 50% of the animals were similar. The duration of the antibody response to HBsAg was studied in mice immunized with the highest doses of the two recombinant vaccine preparations 3 and 6 months after injection. No decrease in the anti-HBs response was observed 6 months after injection. No decrease in the anti-HBs response was observed 6 months after immunization with either of the two vaccine preparations. These results indicate that the baculovirus-derived recombinant HBsAg could serve as an alternative vaccine candidate for hepatitis B virus.

Animals↗

The implications and applications of biostatistical analysis in craniomandibular and orofacial pain disorders.

This article will acquaint the reader with the most commonly used summary statistics and their appropriate use in craniomandibular and orofacial pain disorders. Hopefully it will also encourage the reader to critically examine published papers, experimental design, and statistical treatment of data by asking these questions: Have experiments been properly designed? Has enough information been presented so that research can be repeated? Were subjects randomly assigned and treated? Was the statistical analysis described clearly and succinctly, and was it appropriate? Did the experimental data and results support the conclusions of the article? Were the findings statistically significant, and if so, were they clinically significant and meaningful? Anecdotal clinical studies of temporomandibular disorder sufferers can no longer be considered as the gold standard.

Biometry↗

Nocturnal bruxism and its clinical management.

Most individuals, both adults and children, engage in nocturnal bruxist activity at some point in their lives and to varying degrees. The tissues of the masticatory system will generally adapt to this behavior; however, in some individuals the capacity for adaption will be exceeded by the cumulative forces of this mandibular parafunctional behavior, resulting in pain and dysfunction of the masticatory system. This article discusses the history, nature, causes, and effects of bruxism as well as the diagnosis and therapy.

Adult↗

Amyotrophic lateral sclerosis: thyroid and prolactin hormone changes in thyrotropin-releasing hormone therapy.

13 patients with amyotrophic lateral sclerosis (ALS) were treated with intravenous infusion of thyrotropin-releasing hormone (TRH). In 6 patients 2 mg/day of TRH was i.v. given over 2 hours for 10 days. In 7 others 2 mg/day of TRH was continuously infused by means of a pump. An increase of thyroid hormones related to the duration of the treatment was observed. A surprising finding was the onset of prolactin (PRL) response to growth hormone releasing hormone (GHRH), previously absent.

Amyotrophic Lateral Sclerosis↗

Prolactin response to growth hormone-releasing hormone during chronic thyrotropin-releasing hormone infusion in the treatment of amyotrophic lateral sclerosis.

In six patients suffering from amyotrophic lateral sclerosis we evaluated changes of T4, T3, TSH, PRL, and GH during treatment by continuous iv infusion of TRH for at least 15 days. No clinical improvement was detected. A significant rise of thyroid hormone levels was observed, as well as an upward trend of basal TSH levels and no change of basal PRL and GH levels. TRH acute test-induced TSH and PRL responses became blunted. Treatment provoked also the onset of a responsiveness of PRL to GHRH. The reduced TSH and PRL responses to acute TRH test during treatment could be explained by a down-regulation of TRH pituitary receptors. On the contrary, the onset of PRL responsiveness to GHRH is at present without a satisfactory explanation.

Amyotrophic Lateral Sclerosis↗

Resistance to a long-acting somatostatin analog (SMS 201-995) reversed by surgery in acromegaly.

A 42-year-old woman had acromegaly and a large macroadenoma with supra- and parasellar extension. Her GH levels (median 85 ng/ml, range 63-170 ng/ml) were not responsive to TRH (200 micrograms iv), GHRH (100 micrograms iv) and bromocriptine (Br 2.5 mg po) acute tests; Sm-C level was 8 U/ml. She was treated with octreotide (SMS) (up to 1500 micrograms daily) for 3 months. No changes of clinical, biochemical and radiological findings were seen, therefore she underwent transsphenoidal surgery. After surgery, hypopituitarism and diabetes insipidus appeared: GH levels remained high (median 45 ng/ml; range 37-56 ng/ml), but became responsive to Br acute test. The patient was given SMS again, and this resulted in clinical improvement, marked reduction of GH and Sm-C levels and slight shrinkage of the residual tumor. Speculative hypotheses about this previously unreported phenomenon might be either an excess of both GHRH and somatostatin, caused by a primary increase of dopaminergic tone, or a primary excess only of GHRH; in both cases the surgical lesion of the hypothalamic-pituitary region might have impaired the neurohormones inflow to the residual pituitary and so let SMS and Br exert their inhibitory actions on GH secretion.

Acromegaly↗

Anti-idiotypic antibodies of a predefined specificity generated against CDR3VH synthetic peptides define a private anti-CD4 idiotype.

A synthetic peptide corresponding to the third complementarity determining region (CDR) of the heavy chain (CDR3VH) of anti-Leu3a, a monoclonal anti-CD4 antibody which inhibits HIV gp120 binding to CD4, was used to elicit specific anti-peptide antibodies in rabbits. The anti-peptide antisera showed anti-idiotypic antibody (anti-Id) activity and recognized both the immunizing peptide and the intact cognate protein by ELISA. In addition, the antisera reacted with isolated heavy chains of anti-Leu3a by Western blot analysis. The lack of reactivity with a panel of monoclonal anti-CD4 antibodies suggested that the anti-peptide antisera recognize a private idiotype (Id) associated with the anti-Leu3a CDR3VH region. Further studies demonstrated the inability of the rabbit antisera to inhibit the binding of anti-Leu3a to the CD4 molecule. In addition, soluble recombinant CD4 was unable to inhibit the binding of the rabbit anti-peptide antisera to anti-Leu3a indicating that the CDR3VH region may not be involved in CD4 recognition. Anti-Id containing sera from mice, rabbits and nonhuman primates immunized with the intact anti-Leu3a molecule did not bind the CDR3VH synthetic peptide, suggesting that the corresponding region of anti-Leu3a may not represent an immunodominant idiotypic determinant in thes e species. These results suggest the potential use of synthetic peptides corresponding to immunoglobulin variable (V) region amino acid sequences in generating anti-Id reagents of a predefined specificity. In addition, V-region synthetic peptides may be useful in mapping the idiotopes recognized by an anti-Id response to the cognate molecule.

Amino Acid Sequence↗

Idiotypic cascades associated with the CD4-HIV gp120 interaction: principles for idiotype-based vaccines.

Idiotypes (Id) are antigenic determinants expressed on the variable (V) region of the immunoglobulin molecule. Id-bearing antibodies, or Ab-1, are produced upon stimulation with a given antigen. Ab-1 may elicit the production of anti-idiotypic antibodies (anti-Id) or Ab-2. The anti-Id also expresses Id determinants and may in turn elicit the production of anti-anti-Id or Ab-3. The production of Ab-1, Ab-2, and Ab-3 responses resulting from stimulation with the antigen is representative of components within an Id cascade. The existence of this Id cascade is the basis for the development of Id based strategies for controlling the immune response to infectious agents and tumors. In this review we will focus on several aspects regarding the Id cascades that may be operational during the immune response to the human immunodeficiency virus (HIV). In light of several studies which suggest the existence of Id-anti-Id interactions operating during the course of HIV infection, we will discuss the potential applications of Id based strategies in manipulating the immune response to HIV.

AIDS Vaccines↗

Temporal arteritis.

Temporal arteritis, a vasculitis, affects the large- and medium-sized arteries. This disorder has a largely unknown etiology and mainly occurs in older patients. Headache is the predominant symptom with diplopia usually appearing shortly after. Clinicians must be aware of temporal arteritis because blindness occurs in up to 50% of untreated or misdiagnosed patients.

Aged↗

The effect of long-term pulsatile GnRH administration on the 24-hour integrated concentration of GH in hypogonadotropic hypogonadic patients.

Measurement of integrated concentration of GH by means of continuous withdrawal sampling is a method of evaluating physiological hormonal secretion. Integrated concentration of GH was evaluated in 5 subjects with idiopathic hypogonadal hypogonadism (range 19-27 years) and in a 17-year-old male with idiopathic delay of puberty (5 males, 1 female) before and 30-240 days after the start of pulsatile GnRH administration. Gonadotropins and testosterone or 17 beta-estradiol were restored, whereas 24-h integrated concentration of GH (before therapy 5.4 +/- 1.3 IU/1; during GnRH 8.1 +/- 2.0 IU/1; P less than 0.05) was increased by GnRH therapy. However, no correlation was found between GH levels and sex steroid concentrations during GnRH pulsatile administration. These data further confirm that a physiological increase in gonadotropins and sex steroids can modulate GH synthesis and/or release.

Adult↗

Endogenous opioid blockade and gonadotropin secretion: role of pulsatile luteinizing hormone-releasing hormone administration in anorexia nervosa and weight loss amenorrhea.

In anorexia nervosa alterations in the hypothalamic-pituitary-gonadal unit were previously thought to have been connected to an increase of endogenous opiate tone. The authors tried to prove that the replacement of normal endogenous steroid levels could restore the functional coupling between opiatergic and luteinizing hormone-releasing hormone (LH-RH) neurons in patients with anorexia nervosa. Pulsatile LH-RH therapy has been used to achieve normal ovarian activity. The authors studied gonadotropin levels before and during intravenously (IV) pulsatile LH-RH therapy (50 to 100 ng/kg body weight/90 to 120 minutes) in three anorexia nervosa and two weight loss amenorrhea patients, during both placebo and naloxone administration (2 mg IV bolus plus 4 mg infusion lasting 120 minutes). Before therapy, naloxone administration did not significantly change gonadotropin levels in three out of five patients, while a decrease in gonadotropin levels was observed in the other two subjects. During LH-RH therapy, normal pituitary-gonadal activity was demonstrated and ovulatory cycles were found in all patients. Naloxone administration did not change gonadotropin release during LH-RH therapy. Data could support the hypothesis of either a primitive impairment of LH-RH neurons, or an alteration in central regulation of LH-RH pulsar in anorexia nervosa.

Adolescent↗