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Biomedical subjects

R Attanasio

Publications and source records attributed to R Attanasio.

At least 19 recordsLinked to original sources

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

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

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

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