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Biomedical subjects

E Goldberg

Publications and source records attributed to E Goldberg.

At least 127 records · Page 7Linked to original sources

Antigenic sites of lactate dehydrogenase-C4.

Use of antipeptide antibodies plus a panel of monoclonal antibodies to screen the testicular lactate dehydrogenases should provide highly sensitive discrimination of their evolutionary relatedness. When this is combined with sequence information and peptide synthesis, it will be possible to describe the precise limits of each epitope on the surface of LDH-C4. From the standpoint of contraceptive vaccine development, a synthetic antigen consisting of one or more epitopes can be prepared. This will eliminate the necessity of attempting to isolate antigens from natural products, and will provide a useful strategy for developing this approach to fertility control.

Animals↗

Male-enhanced expression and genetic conservation of a gene isolated with an anti-H-Y antibody.

The hypothesis of the serological H-Y antigen as the inducer molecule for mammalian male sex differentiation has been considered an important working model in developmental biology. However, because of the difficulties involved in its detection, supporting evidence in molecular terms is lacking for this hypothesis. The isolation of the gene for the serological H-Y antigen is essential to the acertainment of its proposed functions. Using recombinant DNA technology and specific anti-H-Y sera we have isolated a candidate gene, the MEA gene, for the serological H-Y antigen. Molecular characterization of the MEA gene shows male-enhanced expression and genetic conservation patterns similar to those attributed to the serological H-Y antigen. The isolation of this candidate gene for the serological H-Y antigen. The isolation of this candidate gene for the serological H-Y antigen would allow further investigations to identify the functions for this molecule in molecular terms.

Aging↗

Non-cross-reactivity of antibodies to murine LDH-C4 with LDH-A4 and LDH-B4.

The induction of infertility by immunization with the sperm-specific lactate dehydrogenase, LDH-C4, suggests its use in a contraceptive vaccine. Development of an immunological contraceptive for human use, however, requires that there be no cross-reactions with somatic tissues. We have demonstrated, using enzyme-linked immunoabsorbence, solid-phase radioimmunoassay, and competitive inhibition radioimmunoassay, that antisera to LDH-C4 is specific and does not cross-react with the somatic isozymes, LDH-A4 and LDH-B4.

Animals↗

Control of fertilization by immunization with peptide fragments of sperm specific LDH-C4.

The use of a well-defined, synthetic antigen is essential to progress in developing a vaccine for fertility control and to establish with certainty the utility of such technology. The studies with LDH-C4 are consistent with the feasibility of using a synthetic antigen in a vaccine to control fertility. LDH-C4 remains the best-developed candidate for future studies. Immunization with LDH-C4 does suppress fertility, and the complete biochemical characterization of this isozyme is well underway. These studies will provide a wealth of synthetic antigens to substitute for the natural product in experiments to determine whether immunologic contraception is appropriate and desirable for wide-scale application in human beings.

Animals↗

Varieties of perseveration: a comparison of two taxonomies.

Two taxonomies of perseveration have been independently developed by Goldberg and Tucker (1979) and Sandson and Albert (1984). They are in remarkable agreement with respect to phenomenology of perseveration but differ in terms of postulated mechanisms. Sandson and Albert propose a separate mechanism for every type, whereas Goldberg and Tucker propose a unitary mechanism which can operate at different levels of neurocognitive hierarchy thus producing different types of perseveration. The issue of neuroanatomical specificity of perseveration is also addressed. It is proposed that clinical features of prefrontal syndromes need not imply the presence of selective structural or biochemical damage to prefrontal cortex, and that a structurally diffuse CNS disease often masquerades as a selective frontal-lobe disease. The difference between structural and functional definitions of focal brain disease is emphasized.

Adult↗

Local reproductive tract immunity to sperm-specific lactate dehydrogenase-C4.

Immunity to sperm-specific lactate dehydrogenase C4 (LDH-C4) results in reduction of fertility in females. Stimulation of a local mucosal immune response to LDH-C4 in the reproductive tract would guarantee the presence of antibodies at the site of fertilization, which should enhance suppression of fertility. After intrauterine immunization with LDH-C4, SJL/J female mice secrete immunoglobulin (Ig)A antibodies specific for LDH-C4 into their uterine fluids. Furthermore, these animals demonstrate a lower pregnancy rate than controls receiving an intrauterine immunization without LDH-C4. Thus, induction of a local immune response is an effective alternative to systemic immunization for administering a contraceptive vaccine.

Animals↗

Fine specificity analysis of lactate dehydrogenase B-specific proliferating T cell clones: implications for the mechanism of alloreactivity.

T cell clones of C57BL/6 origin which recognize porcine lactate dehydrogenase B (LDH-BP) together with the Ab molecule were characterized in terms of fine specificity for both LDH-B and self-major histocompatibility complex determinants. Using antigen-presenting cells from the Ab-mutant strain B6.C-H-2bm12 (bm12), three clonotypes could be distinguished: the first responds to LDH-BP + bm12, the second fails to respond and the third is alloreactive to bm12. The last clone exhibits additional alloreactivities to A molecules expressed in strains of H-2 haplotypes f, r, s, u, w6, w7, w16, w17 and w23. All three clonotypes give identical response patterns to a panel of 17 different dehydrogenase enzymes, and react to the same tryptic peptide of LDH-BP. Thus, these clones appear to recognize the same LDH-B epitope together with at least 3 different determinants of the Ab molecule. The data suggest that alloreactivity is more closely related to T cell specificity for self-major histocompatibility complex than to specificity for foreign antigen.

Animals↗

The antigenicity of synthetic peptide fragments of lactate dehydrogenase C4.

Lactate dehydrogenase C4 (LDH-C4) is an antigenic protein found only in spermatozoa and the mature testis. Synthetic peptides containing the amino acid sequences of the C-subunit, designated MC5-15, MC97-110 and MC211-220, were each conjugated to the carrier proteins diphtheria toxoid or bovine serum albumin. Rabbits immunized with these peptide-carrier conjugates produced antibodies to the peptide that cross-reacted with native LDH-C4. These data support our map that identifies antigenic domains of LDH-C4. Such synthetic peptides will be useful in the design of a contraceptive vaccine.

Animals↗

Antigenic domains of the sperm-specific lactate dehydrogenase C4 isozyme.

Lactate dehydrogenase C4 (LDH-C4) is an antigenic protein that occurs only in spermatozoa and the mature testis. The antibody-combining sites of this enzyme were mapped by measuring the binding of anti-LDH-C4 by isolated peptides. Pure mouse LDH-C4 was digested with trypsin, and the resulting fragments were fractionated by reverse-phase high-pressure liquid chromatography. Rabbit anti-mouse LDH-C4 bound to 13 pure peptides. Amino acid compositions and partial or complete sequencing by the Edman degradation was used to identify eight of these fragments in the complete structure of the molecule. The relationship between structure and antigenicity of these peptides is discussed in detail. These data fit best to the domain model of protein antigenicity. This antigenic map of LDH-C4 will be useful in the design of a synthetic contraceptive vaccine.

Amino Acid Sequence↗

Serum antibodies to LDH-C4.

Human sera from the WHO Reference Bank were tested by a liquid phase radioimmunoassay for antibodies to the sperm-specific form of lactate dehydrogenase (LDH-C4; LDH-X). Modestly elevated levels of antibodies were detected in about 10% of infertile males and females and in about 20% of vasectomized males, as well as in a few cases in other categories. The occurrence of this anti-LDH-C4 activity was without overt correlation with other anti-sperm antibody assays. The primary advantage of the radioimmunometric assay is its absolute specificity for a sperm antigen. These findings lend support to contraceptive vaccine development based on LDH-C4 antigenicity.

Animals↗

Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound.

Doppler ultrasound examination was performed in 69 patients with a variety of cardiopulmonary disorders who were undergoing bedside right heart catheterization. Patients were classified into two groups on the basis of hemodynamic findings. Group I consisted of 20 patients whose pulmonary artery systolic pressure was less than 35 mm Hg and Group II consisted of 49 patients whose pulmonary artery systolic pressure was 35 mm Hg or greater. Tricuspid regurgitation was detected by Doppler ultrasound in 2 of 20 Group I patients and 39 of 49 Group II patients (p less than 0.001). Twenty-six of 27 patients with pulmonary artery systolic pressure greater than 50 mm Hg had Doppler evidence of tricuspid regurgitation. In patients with tricuspid regurgitation, continuous wave Doppler ultrasound was used to measure the velocity of the regurgitant jet, and by applying the Bernoulli equation, the peak pressure gradient between the right ventricle and right atrium was calculated. There was a close correlation between the Doppler gradient and the pulmonary artery systolic pressure measured by cardiac catheterization (r = 0.97, standard error of the estimate = 4.9 mm Hg). Estimating the right atrial pressure clinically and adding it to the Doppler-determined right ventricular to right atrial pressure gradient was not necessary to achieve accurate results. These findings indicate that tricuspid regurgitation can be identified by Doppler ultrasound in a large proportion of patients with pulmonary hypertension, especially when the pulmonary artery pressure exceeds 50 mm Hg. Calculation of the right ventricular to right atrial pressure gradient in these patients provides an accurate noninvasive estimate of pulmonary artery systolic pressure.

Adult↗

Akinesia, tardive dysmentia, and frontal lobe disorder in schizophrenia.

Two iatrogenic effects of antipsychotic medications other than tardive dyskinesia have been recently described in schizophrenic populations: akinesia and tardive dysmentia. These effects involve activational, cognitive, and affective rather than motor changes, and closely resemble two most common prefrontal syndromes: dorsolateral and fronto-orbital/mediobasal. It is possible that the widely reported "frontal lobe dysfunction" in some chronic schizophrenic patients at least in part reflects iatrogenic changes in the mesolimbic/mesocortical dopamine system, which projects extensively into prefrontal areas. The degree of iatrogenic versus genuine contribution to the frontal lobe dysfunction in schizophrenia needs to be ascertained further, and the heterogeneity of known frontal lobe syndromes must be taken into account in describing schizophrenic populations. The mechanisms of noniatrogenic contributions to the frontal lobe dysfunction in schizophrenia may reflect a variety of anatomical sources and require further examination.

Antipsychotic Agents↗

Induction of cell-mediated cytotoxic immunity to sperm-specific lactate dehydrogenase-C4 in SJL/J female mice.

SJL/J female mice were tested for a cell-mediated cytotoxic response to sperm-specific lactate dehydrogenase C4 (LDH-C4). We demonstrated this response with a 51chromium release assay. Mouse LDH-C4 was coupled to EL-4 tumor cells. These cells were then labeled with 51Cr and mixed with splenocytes from LDH-C4-immune and -nonimmune mice. Specific lysis of the tumor cells by splenocytes from LDH-C4-immune mice was detected at 7 days and 14 days following a single footpad immunization. Since LDH-C4 is present on the surface of sperm, these results support the suggestion that cytotoxic removal of sperm from the female reproductive tract is one of the mechanisms whereby fertility is reduced following immunization with this enzyme.

Animals↗

Binding of antibodies against antigenic domains of murine lactate dehydrogenase-C4 to human and mouse spermatozoa.

Peptide fragments of lactate dehydrogenase-C4 (LDH-C4) that contain antigenic sequences of the native protein have been identified. The present study describes the binding to murine and human spermatozoa of antibodies that were produced against synthetic peptides containing two of these sequences. Rabbits were immunized with peptides designated MC5-15 and MC211-220, conjugated to diphtheria toxoid (DT). Antisera from these rabbits were tested for binding to washed mouse epididymal sperm or human ejaculated spermatozoa using a solid-phase radioimmunoassay. Antisera bind to mouse sperm in this system at dilutions of 1:64,000. When these antisera are first absorbed with the native LDH-C4 molecule, significant inhibition of binding to sperm results. Antisera to both DT-MC5-15 and DT-MC211-220 bind to human sperm with similar but weaker patterns than seen with mouse sperm. These data indicate that the immune response to synthetic peptides containing antigenic sequences of LDH-C4 includes antibodies that specifically bind to this enzyme on the surface of sperm. In addition, there are shared antigenic sequences between mouse and human LDH-C4, including the MC5-15 and MC211-220 peptides.

Amino Acid Sequence↗