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Clinicians affiliated with medical human rights programs throughout the United States perform forensic evaluations of asylum seekers. Much of the best practice literature reflects the perspectives of clinicians and attorneys, rather than the viewpoints of immigration judges who incorporate forensic reports into their decision-making. The purpose of this study was to assess former immigration judges' perspectives on forensic mental health evaluations of asylum seekers. We examined the factors that immigration judges use to assess the affidavits resulting from mental health evaluations and explored their attitudes toward telehealth evaluations. We conducted semistructured interviews in April and May 2020 with nine former judges and systematically analyzed them using consensual qualitative research methodology. Our findings were grouped in five domains: general preferences for affidavits; roles of affidavits in current legal climate; appraisal and comparison of sample affidavits; attitudes toward telephonic evaluations; and recommendations for telephonic evaluations. Forensic evaluators should consider the practice recommendations of judges, both for telephonic and in-person evaluations, which can bolster the usefulness of their evaluations in the adjudication process. To our knowledge, this is the first published study to incorporate immigration judges' perceptions of forensic mental health evaluations, and the first to assess judges' attitudes toward telephonic evaluations., (© 2022 American Academy of Psychiatry and the Law.)

Background: Postoperative pain after fixation of ankle fractures has a substantial effect on surgical outcome and patient satisfaction. Patients requiring large amounts of narcotics are at higher risk of long-term use of pain medications. Few prospective studies investigate patient pain experience in the management of ankle fractures., Methods: We prospectively evaluated the pain experience in 63 patients undergoing open reduction and internal fixation of ankle. The Short-Form McGill Pain Questionnaire was administered preoperatively and postoperatively (PP) at 3 days (3dPP) and 6 weeks (6wPP). Anticipated postoperative pain (APP) was recorded., Results: No significant differences were found between PP, APP, and 3dPP; however, 6wPP was markedly lower. Significant correlations were found between PP and APP and between preoperative and postoperative Short-Form McGill Pain Questionnaire scores. PP and APP were independent predictors of 3dPP; however, only APP was predictive of 6wPP. Sex, age, and inpatient versus outpatient status were not notable factors. No statistically significant differences were found in pain scores between fracture types., Conclusions: Both preoperative pain severity and anticipated postoperative pain are predictive of postoperative pain levels. Orthopaedic surgeons should place a greater focus on the postoperative management of patient pain and expectations after surgical procedures.

The ability to produce monoclonal antibodies (Mabs) in plants offers the opportunity for the development of an inexpensive method of mucosal immunoprotection against sexually transmitted diseases. To investigate the suitability of plant-expressed Mabs for vaginal preventive applications, we compared a humanized anti-herpes simplex virus 2 (HSV-2) Mab expressed in mammalian cell culture with the same antibody expressed in soybean. We found these Mabs to be similar in their stability in human semen and cervical mucus over 24 h, their ability to diffuse in human cervical mucus, and their efficacy for prevention of vaginal HSV-2 infection in the mouse.

The murine monoclonal antibody BR55-2 is directed against the tumor-associated antigen Lewis Y oligosaccharide. The Lewis Y core antigen is a difucosylated structure consisting of four hexose units. Analysis of binding profiles of lactoseries isomeric structures by BR55-2 suggest that the binding epitope includes the OH-4 and OH-3 groups of the beta-D-galactose unit, the 6-CH3 groups of the two fucose units and the N-acetyl group of the subterminal beta-D-N-acetylglucosamine (beta DGlcNAc). To elucidate the molecular recognition properties of BR55-2 for the Y antigen, BR55-2 was cloned, sequenced and its three-dimensional structure was examined by molecular modeling. The crystal structure of BR96, another anti-Lewis Y antibody, solved in complex with a nonoate methyl ester Lewis Y tetrasaccharide, and the lectin IV protein in complex with a Lewis b tetrasaccharide core were used as a guide to probe the molecular basis for BR55-2 antigen recognition and specificity. Our modeling study shows that BR55-2 shares similar recognition features for the difucosylated type 2 lactoseries Lewis Y structure observed in the BR96-sugar complex. We observe that a major source of specificity for the Lewis Y structure by anti-Y antibodies emanates from interaction with the beta-D-N-acetylglucosamine residue and the nature of the structures extended at the reducing site of the fucosylated lactosoamine.

ABL 364 is a murine monoclonal IgG3 antibody directed against the Lewis Y carbohydrate antigen (Le(y)) expressed on the surface of many epithelial cell tumors. The antibody mediates cytotoxicity via activation of human complement or human effector cells, and has been evaluated in several clinical trials including two Phase I/II trials in relapsed small cell lung cancer and metastatic breast cancer. To improve the effector functions of the antibody, increase its half-life in circulation, and avoid the human antimouse antibody response, two chimeric and several humanized antibodies were constructed for evaluation. The chimeric IgG1 is more potent than the murine IgG3 in tumor cell lysis via activation of human peripheral mononuclear cells (10-fold), but somewhat less effective in complement-dependent lysis (2-3 fold). The chimeric IgG3 is slightly less potent than the IgG1. A humanized IgG1 was constructed by combining the complementarity-determining regions of the ABL 364 antibody with human framework and constant regions. Several additional variants were subsequently constructed to improve the binding affinity and increase expression of the antibody. Two of the variants, designated I and K, differ by a single amino acid at position 75 of the heavy chain. Both variants have affinity within 2-fold of the chimeric IgG1 antibody and retain the cytolytic activities toward tumor cell lines. However, it was possible to express variant K at a significantly higher level (5- 10-fold) than variant I. Pharmacokinetics of the humanized ABL 364 antibody variant K was compared with that of the parent murine antibody in rhesus monkeys. It was shown that the terminal half-life of the humanized antibody in rhesus monkeys is 14-20 days, with a mean of 16.3 days, while that of the parent murine antibody is only 1.9 days.

Seven neutralizing murine monoclonal antibodies specific for the glycoprotein H of human cytomegalovirus were produced and used to construct a topological map of two nonoverlapping antigenic sites that are bridged by a third antigenic site. Neutralization assays with 15 laboratory or clinical human cytomegalovirus strains indicated that the monoclonal antibodies recognize three antigenically variable and three conserved epitopes within the three antigenic sites. The variable-domain genes encoding monoclonal antibodies representing each of the three antigenic sites were cloned and sequenced, and molecular models of their binding sites were generated. Conformational differences in the antibody-binding sites suggested a structural basis for experimentally observed differences in gH epitope recognition.

Human-mouse chimeric immunoglobulins G1 and G3 (IgG1 and IgG3) (ChG1, ChG3) and "complementarity-determining region"-grafted, humanized IgG1 and IgG3 (HuG1, HuG3) constructs of the mouse monoclonal antibody (mAb) M195 were characterized. M195 is a murine immunoglobulin G2a (IgG2a), anti-CD33 mAb, specifically reactive with acute myelogenous leukemia cells, that is active as an antileukemia agent in humans. The new mAb constructs maintained specificity and biological function, including rapid internalization after binding to the cell surface, which has been important for delivery of therapeutic isotopes in patients. Although previously reported complementarity-determining region-grafted mAbs had reduced avidities, the HuG1 and HuG3 M195 showed up to an 8.6- and 4-fold higher binding avidity, respectively, than the original murine mAb. All constructs were effective at mediating rabbit complement-mediated cytotoxicity against HL60 targets. Fibroblasts transfected with CD33 genes and expressing high levels of CD33 antigen were also lysed in the presence of human complement, but HL60 cells or fibroblasts with lower CD33 levels were not killed. Thus, the inability of M195 and constructs to kill HL60 targets with human complement is due to the much lower antigen density on HL60 cells compared to CD33+ fibroblasts. Unlike the murine M195, the chimeric and humanized M195 demonstrated antibody-dependent cell-mediated cytotoxicity using human peripheral blood mononuclear cells as effectors. Because the chimeric and humanized M195 have improved avidities as compared to the original M195 and have, in addition, the potential to avoid human anti-mouse antibody responses and to recruit human effector functions, these new constructs may be useful therapeutically, either alone or conjugated to toxins or isotopes, in the treatment of acute myelogenous leukemia.

Humanized IgG1 M195 (HuG1-M195), a complementarity determining region-grafted recombinant monoclonal antibody, is reactive with CD33, an antigen expressed on myelogenous leukemia cells. M195 is in use in trials for the therapy of acute myelogenous leukemia. Since biological activity of IgG may depend, in part, on multimeric Fab and Fc clustering, homodimeric forms of HuG1-M195 were constructed by introducing a mutation in the gamma 1 chain CH3 region gene to change a serine to a cysteine, allowing interchain disulfide bond formation at the COOH terminal of the IgG. Despite similar avidity, the homodimeric IgG showed a dramatic improvement in the ability to internalize and retain radioisotope in target leukemia cells. Moreover, homodimers were 100-fold more potent at complement-mediated leukemia cell killing and antibody-dependent cellular cytotoxicity using human effectors. Therefore, genetically engineered multimeric constructs of IgG may have advantages relative to those forms that are found naturally.

Protein engineering has made it possible to combine the binding sites of murine antibodies with human antibody regions. Antibodies constructed in this way have important advantages for therapy.

Antibody therapy holds great promise for the treatment of cancer, autoimmune disorders, and viral infections. Murine monoclonal antibodies are relatively easy to produce but are severely restricted for therapeutic use by their immunogenicity in humans. Production of human monoclonal antibodies has been problematic. Humanized antibodies can be generated by introducing the six hypervariable regions from the heavy and light chains of a murine antibody into a human framework sequence and combining it with human constant regions. We humanized, with the aid of computer modeling, two murine monoclonal antibodies against herpes simplex virus gB and gD glycoproteins. The binding, virus neutralization, and cell protection results all indicate that both humanized antibodies have retained the binding activities and the biological properties of the murine monoclonal antibodies.

A cell-surface receptor for the mammalian reovirus type 3 hemagglutinin was isolated by using antiidiotypic anti-receptor antibodies. The receptor is a glycoprotein with a molecular mass of 67,000 daltons and a pI of 5.9. Evidence that the isolated structure represents the reovirus receptor was obtained by electrophoretic immunoblot studies, which demonstrated that the 67,000-dalton glycoprotein is the only cell-surface structure recognized by both reovirus type 3 and the anti-receptor immunoglobulin. Comparison of the reovirus receptor on murine thymoma (R1.1) and rat neuroblastoma (B104) cells indicated that similar structures on the cell surface are recognized by the reovirus type 3 and the anti-receptor antibodies as previously suggested from cellular and binding studies. This receptor was found on mouse, rat, monkey, and human cells. Furthermore, diverse tissue types, including lymphoid and neuronal cells, express the receptor structure. The receptor structure is discussed in terms of its role in mediating viral tropism and as an essential cell-surface protein.

X-ray absorption spectroscopy has been used to study the dimeric iron center in azidomethemerythrin from Phascolopsis gouldii. Absorption edge data confirm that the two iron atoms are present as Fe(III) and suggest a hexa-coordination site for each of the iron atoms. The extended x-ray absorption fine structure (EXAFS) analysis provides direct structural evidence of a mu-oxo bridge between the two iron atoms at an average Fe-O distance of 1.71-1.76 A. Analysis using a multiple-scattering formalism calculates upper limits of 165 degrees for the Fe-O-Fe bridging angle and 3.38 A for the Fe-Fe distance. This result agrees with current crystallographic models being determined by refinement of structures of two azidomethemerythrins.

The monoclonal anti-idiotypic antibody (mAb2) 87.92.6 directed against the 9B.G5 antibody specific for the virus neutralizing epitope on the mammalian reovirus type 3 hemagglutinin was previously demonstrated to express an internal image of the receptor binding epitope of the reovirus type 3. Furthermore, this mAb2 has autoimmune reactivity to the cell surface receptor of the reovirus. The nucleotide and deduced amino acid sequences of the 87.92.6 mAb2 heavy and light chains are described in this report. The sequence analysis reveals that the same heavy chain variable and joining (VH and JH) gene segments are used by the 87.92.6 anti-idiotypic mAb2 and by the dominant idiotypes of the BALB/c anti-GAT (cGAT) and anti-NP (NPa) responses. [GAT; random polymer that is 60% glutamic acid, 30% alanine, and 10% tyrosine. NP; (4-hydroxy-3-nitrophenyl)-acetyl.] Despite extensive homology at the level of the heavy chain variable regions, the NPa positive BALB/c anti-NP monoclonal antibody 17.2.25 binds neither 9B.G5 nor the cellular receptor for the hemagglutinin. Amino acid sequence comparison between the viral hemagglutinin and the 87.92.6 mAb2 light chain "internal image," reveals an area of significant homology indicating that antigen mimicry by antibodies may be achieved by sharing primary structure.

The mechanism by which viruses bind to and infect specific tissues to cause disease has only recently begun to be understood. The mammalian reoviruses provide an especially attractive model for studying the details of cell surface recognition. The cell and tissue tropism of reovirus is determined by a portion of the viral hemagglutinin termed the neutralization domain. We have reported previously on the generation of both monoclonal and polyclonal anti-idiotypic antibodies that mimic the viral hemagglutinin in the specificity of binding to the reovirus receptor. By using these anti-idiotypic antibodies as specific probes, we have successfully isolated the mammalian reovirus receptor from neuronal and lymphoid cells. In the present study, we report that the reovirus receptor is structurally similar to the mammalian beta-adrenergic receptor. This conclusion is based on the following observations: (i) purified beta-adrenergic receptor is immunoprecipitable by anti-reovirus receptor antibody; (ii) purified reovirus receptor obtained from murine thymoma cells and beta-adrenergic receptor obtained from calf lung exhibit identical molecular masses and isoelectric points; (iii) trypsin digests of purified reovirus and beta-adrenergic receptors display indistinguishable fragment patterns; (iv) purified reovirus receptor binds the beta-antagonist [125I]iodohydroxybenzylpindolol and this binding is blocked by the beta-agonist isoproterenol.

By atomic absorption analysis, we determined that the reovirus outer capsid protein sigma 3, which binds double-stranded RNA (dsRNA), is a zinc metalloprotein. Using Northwestern blots and a novel zinc blotting technique, we localized the zinc- and dsRNA-binding activities of sigma 3 to distinct V8 protease-generated fragments. Zinc-binding activity was contained within an amino-terminal fragment that contained a transcription factor IIIA-like zinc-binding sequence, and dsRNA-binding activity was associated with a carboxy-terminal fragment. By these techniques, new zinc- and dsRNA-binding activities were also detected in reovirus core proteins. A sequence similarity was observed between the catalytic site of the picornavirus proteases and the transcription factor IIIA-like zinc-binding site within sigma 3. We suggest that the zinc- and dsRNA-binding activities of sigma 3 may be important for its proposed regulatory effects on viral and host cell transcription and translation.