Mitogenic properties of a bispecific single-chain Fv-Ig fusion generated from CD2-specific mAb to distinct epitopes.

The combination of anti-CD2 mAb 9.6 and 9-1, specific for distinct epitopes, induces proliferation of resting human T cells. The mitogenic activity of this mAb mixture depends upon accessory cells and the 9-1 mAb Fc domain. To further study the functional properties of these mAb, their variable regions were cloned and expressed as monospecific single-chain Fv (scFv) proteins fused to the human IgG1 Fc domain (scFvIg). A novel bispecific scFvIg was constructed by cloning the two monospecific scFv binding sites in tandem, with the 9.6 scFv placed N-terminal to the 9-1 scFvIg. Monospecific scFvIg binding to CD2 was comparable to that of the corresponding parental mAb, while the bispecific scFvIg exhibited binding activity similar to that of the 9-1 scFvIg. The combination of 9.6 scFvIg and 9-1 mAb was mitogenic, whereas mixtures including the 9-1 scFvIg were non-stimulatory, confirming the unique properties of the 9-1 IgG3 Fc. Without the IgG3 tail, the bispecific 9.6/9-1 scFvIg was directly mitogenic and was a more potent mitogen than the mAb mixture, but was accessory cell dependent. Unlike the combination of mAb, the bispecific reagent did not directly mobilize calcium in T cells. In comparison to the mAb mixture, bispecific 9.6/9-1 scFvIg-mediated stimulation of a mixed lymphocyte reaction was significantly more resistant to inhibition of the CD28 co-stimulatory pathway by the inhibitor CTLA-4-Ig. These results show that expression of the 9.6 and 9-1 binding sites together on a bispecific scFvIg increased the mitogenic properties of the mAb and altered the degree of accessory cell signals required for T cell activation.

Ambiguity in the "Nursing Statement on assisted Suicide".

Nursing is multidimensional, interactive, interdisciplinary, and complex. Almost anything that can be said about nursing can be said another way. Some things worth being said and heard will not follow the norms of journal presentation. A forum accommodates the emerging voice, the new format, the innovative approach. Nursing Forum, in an effort to honor the "independent voice" in nursing, presents here the voice who elects to enter the dialogue, but who does so "in another way."

Anti-idiotypic antibody to the V3 domain of gp120 binds to vimentin: a possible role of intermediate filaments in the early steps of HIV-1 infection cycle.

Although the CD4 molecule is the major cellular receptor for human immunodeficiency virus (HIV), several lines of evidence suggest participation of additional molecules that are engaged after the binding of HIV to the CD4 receptor and that may facilitate viral entry into the target cell. Some of the post-CD4 binding, perfusion events involve the third hypervariable region (V3 loop) of the viral envelope protein gp120. To identify cellular proteins that interact with the V3 loop, we chose as a probe an antiidiotypic monoclonal antibody (MAb), anti-id2, which was prepared against the neutralizing MAb 110.4 that binds the V3 domain in the envelope glycoprotein gp120 of the LAI isolate of HIV-1. Anti-id2 reacted specifically with a 55- to 60-kDa protein in human T cell and monocytoid cell lines, and in a mouse melanoma cell line. This protein was identified immunologically and by protein sequence analysis as vimentin, an intermediate filament protein of lymphoid and other cells of mesodermal origin. Antiserum raised against vimentin inhibited nuclear translocation of HIV-1 DNA following infection of monocytes and CD4+ T cells with live virus, and reduced the amount of HIV-1 gag-specific RNA in the nuclei of monocytes following inoculation with HIV-1 pseudovirions. These data suggest that vimentin may participate in the early steps of HIV-1 replication, perhaps during the uptake of HIV-1 preintegration complexes into the nuclear compartment.

Amniotic band syndrome in fetal lambs. I: Fetoscopic release and morphometric outcome.

A fetal lamb model of amniotic band syndrome (ABS) was developed to study the pathophysiology of banded extremities and evaluate the possibility of in utero treatment with the potential for functional recovery. Eight fetal lambs underwent banding of their extremities with umbilical tape at 100 days' gestation. Two lambs aborted after the open fetal surgery. The limbs of two unoperated newborn lambs served as controls in addition to five sham-operated control limbs that had no bands applied. Nine limbs were banded without reducing blood flow assessed by laser doppler (group 1), and 6 limbs were similarly banded and released fetoscopically at 125 days' gestation. Four limbs were banded, with a mean reduction in blood flow to the limb of 18.7% (group 2) by laser doppler flowmeter. Shortly after birth the lambs were killed, and segmental limb length, circumference, joint range of motion, and histology were evaluated. At birth, banded limbs showed marked brawny edema and absence of wool distal to the band. Segmental limb measurements showed shorter distal forelimbs in banded limbs compared with controls (10.97 +/- 0.59 versus 12.98 +/- 0.69, P < .05). Banded limbs were associated with progressive increase in hoof circumference (P < .03) and a decrease in joint range of motion (P < .003). In sharp contrast, there were no differences between fetoscopically released limbs and control limbs in any of the parameters measured. Histology of banded extremities showed edema, venous and lymphatic congestion, and fibrosis compared with controls. This model of ABS in fetal lambs is simple, reproducible, and replicates all the clinical features of extremity ABS.(ABSTRACT TRUNCATED AT 250 WORDS)

Dual specificity of a monoclonal anti-idiotypic antibody for HIV-1 neutralizing monoclonals 110.3 and 110.4 as well as the V3 loop of gp120.

Monoclonal antibodies (MAbs) 110.3 and 110.4 bind an epitope at the tip of the third hypervariable region (V3) of the envelope protein gp120 of human immunodeficiency virus type 1 (HIV-1). These MAbs inhibit HIV-induced syncytium formation and neutralize cell-free virus infection. Anti-idiotypic MAb alpha-id8, generated against 110.3, was found to mimic the V3 loop of gp120, as demonstrated by competition ELISA and by the generation of anti-anti-idiotypic sera which bound gp120 and a peptide representing the tip of the V3 loop. Interestingly, alpha-id8 itself also reacted specifically with both gp120 and the V3 loop peptide. Thus, alpha-id8 both mimics and binds directly to the V3 loop, suggesting that the V3 loop of gp120 may associate with itself.

Letter to my children about sex and the catholic church.

This essay is directed to a younger generation. It summarizes the conflicting traditions in the Catholic community today: official Church teaching (represented by "Humanae Vitae" and "Veritatis Splendor"), liberal theologians like Charles Curran (who occasioned this letter), and ordinary Catholics struggling in an imperfect world. The paper attempts to integrate values from three traditions, those associated with respect for new life, a loving relationship, and playfulness. The resulting synthesis offers a spiritually and psychologically viable option worth considering, the author believes.

Nursing responsibility for the placebo effect.

The placebo effect is a common phenomenon in therapy and research but has received very little attention as such in nursing research. This article reviews some of the literature which shows the placebo effect, which can be positive or negative, is a significant force. Then it is argued that, while all health professionals have a general obligation to benefit their patients, nursing has a special, specific obligation to enhance the placebo effect, to maximize a positive effect and minimize a negative effect. Nursing education, current policy statements, and circumstances of clinical practice explain this obligation. Nursing research is needed to clarify the multiple ways in which the social and physical environment can trigger a placebo effect. As nursing expands its knowledge of this effect, it can begin to educate patients to the self-care implications of this pervasive but misunderstood phenomenon.

A pyrrhic victory over the RCT?

Where does the moral authority reside to determine what shall be the norms of conduct within a profession? Key documents in nursing, especially "A Social Policy Statement," are analyzed. From this literature it is apparent that nursing is committed to the philosophy that society "owns" the profession. Consequently, moral authority is rooted in the general public. Examining nursing reactions to the registered care technician (RCT) with this philosophy for consistency, we conclude that in this case nursing did not clearly acknowledge the moral authority of society. The public record of the debate suggests that nursing, like medicine, is guilty of a form of paternalism (i.e., nursing is in the best position to decide what is best for society). Nursing needs to evaluate its level of awareness with regard to stated social policy philosophy and the extent to which this philosophy is consciously used to focus discussion about such issues as are raised by the RCT. Most important, if nursing sincerely believes in the moral authority of society, the profession has an obligation to devise creative means of involving society in more direct ways in decision making about health care priorities.

Antigenic heterogeneity in the 115,000 Mr major surface antigen of Trichomonas vaginalis.

The 115,000-molecular-weight antigen of Trichomonas vaginalis was characterized using monoclonal antibodies developed to three different strains of T. vaginalis and one strain of Tritrichomonas foetus. The antigen was found to be present on all strains or isolates of T. vaginalis examined and was demonstrated to be located on the external surface plasma membrane by agglutination assays and complement-mediated lysis assays. Characteristics of the antigen were assessed with a proteolytic enzyme and periodate oxidation. Periodate treatment of whole T. vaginalis abrogated binding for eight antibodies while use of pronase-treated antigen resulted in loss of antibody binding for two different antibodies. Screening of 19 axenized clinical isolates of T. vaginalis and one strain each of T. foetus and Giardia lamblia with type-specific antibodies delineated three major groups of T. vaginalis based on antigenic specificities (epitope distributions) within the 115,000-molecular-weight antigen. In addition, one epitope of the 115,000-molecular-weight antigen was found only on the immunizing strain. Two epitopes were present on all T. vaginalis isolates as well as T. foetus and G. lamblia. One epitope was common to all T. vaginalis except one. A minimum of six different epitopes of the 115,000-molecular-weight antigen were identified. Antigens purified with type-specific or "common" monoclonal antibodies shared the same partial peptide maps demonstrating relatedness.

Natural death and Christian fasting.

The Christian has a unique resource for responding to the problem of how competent adults can exercise responsibly the right to control the last stages of their living/dying. Recent natural death legislation offers only a partial solution, because it does not specify what counts as life-sustaining procedures which may be discontinued if the individual fills out a directive to the physician. One of the most troublesome questions continues to be whether the withholding or withdrawal of artificial feeding, or indeed natural feeding, is ever justifiable. An adaptation of principles included in the Christian idea of fasting seems to provide adequate criteria for determining when forgoing nourishment by the terminally ill adult is morally justifiable.

Identification of a surface antigen of Trichomonas vaginalis.

A major surface antigen of Trichomonas vaginalis was purified by using three independently derived monoclonal antibodies (two immunoglobulin M and one immunoglobulin G1) prepared against T. vaginalis PHS-2J. A 115,000-molecular-weight antigen and one or more components with a molecular weight of 58,000 to 64,000 were recovered when any of the three antibodies was used as an immunoadsorbent. The purified antigen reacted with all three monoclonal antibodies in an enzyme-linked immunosorbent assay, indicating that the antibodies recognized the same antigen but not necessarily the same determinant. The purified antigen was sensitive to both pronase digestion and periodate oxidation. The antigen was shown to be on the external surface of some but not all T. vaginalis isolates by agglutination of live organisms with the monoclonal antibodies.

Specific and common antigens of Trichomonas vaginalis detected by monoclonal antibodies.

Monoclonal antibodies to Trichomonas vaginalis were prepared by immunizing mice with a cloned isolate of T. vaginalis. Eight antibodies reacted with the same four isolates or strains but did not react with the other T. vaginalis strains or isolates tested. All eight antibodies reacted uniformly with both the body and flagella of T. vaginalis in the immunofluorescence assay but were unreactive by immunoblotting. The antigen(s) recognized by these antibodies was determined to be present on the surface membrane by indirect immunofluorescence assay of live organisms. The antigen(s) was found to be sensitive to periodate oxidation but resistant to pronase digestion. In addition, one monoclonal antibody was derived which reacted with all T. vaginalis isolates or strains tested, as well as with Trichomonas gallinae, Tritrichomonas foetus, and Giardia lamblia. This antibody reacted with the body but not the flagella of Formalin-fixed protozoa in the immunofluorescence assay but failed to react with live organisms. The antigen was found to be periodate resistant but pronase labile. In the immunoblot assay, this antibody detected a single T. vaginalis polypeptide with a molecular weight of 62,000.