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Biomedical subjects

R L Wasserman

Publications and source records attributed to R L Wasserman.

17 recordsLinked to original sources

Persistent enterovirus infection in culture-negative meningoencephalitis: demonstration by enzymatic RNA amplification.

Chronic meningoencephalitis due to enterovirus infection can occur in patients with antibody deficiencies. A modified polymerase chain reaction technique demonstrated persistent echovirus 11 infection in such a patient, despite negative routine viral cultures and negative routine nucleic acid hybridization. Although the sequence of echovirus 11 has not yet been determined, genomic conservation among the enteroviruses is significant, permitting detection of echovirus 11 with a primer pair and probe derived from enterovirus serotypes that have been fully sequenced. This study provides the first definitive evidence for the persistence of enterovirus infection with negative viral cultures.

Agammaglobulinemia

Lack of transmission of human immunodeficiency virus from infected children to their household contacts.

The possibility of transmission of the human immunodeficiency virus (HIV) from infected children to their contacts has been confronted in households, schools, day-care centers, and other child care settings. Cases reported to the Centers for Disease Control and several studies of close contacts of HIV-infected patients suggested that the risk of transmission in these settings is extremely low. However, most of these studies involved infected adults or older children. Younger children, who drool, bite, mouth toys, and are incontinent, may be more likely to transmit HIV in these settings. To assess this possibility, the authors tested 89 members of households in which 25 children with HIV infection, most of whom were preschool-aged, resided. Household members had close personal contact with the infected children. They shared many items likely to be soiled with blood and body fluids, such as toys, toothbrushes, eating utensils, toilets, and bathtubs. Hugging, kissing, sharing a bed, and bathing together were common. Household members were tested no sooner than 4 months after initial contact with the infected child, to allow adequate time for sero-conversion. All 89 participating household members were anti-HIV seronegative, and 78 who were tested were serum p24 antigen negative. It was concluded from this study and other evidence that the risk of transmission from children to their contacts is extremely low and has not been clearly documented in the household setting.

Acquired Immunodeficiency Syndrome

Complete protein sequences of the variable regions of the cloned heavy and light chains of a human anti-cytomegalovirus antibody reveal a striking similarity to human monoclonal rheumatoid factors of the Wa idiotypic family.

The complete amino acid and nucleotide sequences of the variable regions of the heavy and light polypeptide chains of a human neutralizing IgGl anti-cytomegalovirus (CMV) antibody reveal a striking homology to IgM rheumatoid factors (RFs) of the Wa idiotypic family. The anti-CMV antibody and Wa RFs have in common VKIIIb, JKl, and VHIa gene segments but use different DH and JH gene segments. The anti-CMV antibody does not have RF activity and does not express the Wa idiotype. The Wa RFs do not have anti-CMV activity. A subset of Wa RFs, however, and the anti-CMV antibody do share several idiotypes on the VHIa and VKIIIb polypeptides. Since there are major differences in the antigen binding characteristics and some of the other expressed idiotypes, these data suggest that the D and J region amino acids are crucial to such specificities. Although the use of such highly homologous gene segments in different immune responses is well-documented in murine systems, these data represent the first such example in the human.

Amino Acid Sequence

In vitro stimulation prior to fusion generates antigen-binding human-human hybridomas.

Production of useful human monoclonal antibodies has been limited by the inability to reliably generate and isolate antigen-specific B cells by in vivo immunization. An in vitro culture system employing antigen and mitogen to stimulate lymphocytes derived from solid lymphoid organs has been developed. Human tonsilar or splenic lymphocytes were stimulated in vitro with antigen and mitogen in short term culture and then fused with either of two enzyme deficient human B cell lines. This approach appears to expand antigen-specific B cell clones prior to fusion resulting in the production of a significant number of antigen-binding human hybridoma antibodies. The system has been effective in the production of human monoclonal antibodies following stimulation with KLH-ARS, a soluble antigen, and intact group B streptococcus, a particulate antigen. Hybridomas have been produced by fusion with two distinct parental human B cell lines supporting the previously reported observation that human B lymphoblastoid cell lines representing different stages of B cell differentiation may be useful fusion partners. The utility of the in vitro stimulation system in producing human-human hybridomas secreting antibody directed against two distinct classes of antigens establishes this approach as a generally useful method for the production of human monoclonal antibodies.

Antibodies, Monoclonal

Ataxia-telangiectasia associated with sarcoidosis.

Ataxia-telangiectasia and sarcoidosis are diseases characterized by abnormalities of the immune system. We examined a 13-year-old female with ataxia-telangiectasia who developed atrophic, violaceous plaques of the skin and a destructive, polyarticular arthritis. The histologic features of both skin and synovium were most consistent with a diagnosis of sarcoidosis. Interaction of these two immunologic disorders may have resulted in the unusual features of this patient's disease.

Adolescent

Caustic substance injuries.

Caustic and corrosive substance ingestions are a significant cause of early and late morbidity and may cause esophageal carcinoma after a long latent period. Initial management should be directed at the assurance of adequate ventilation and cardiovascular stability as well as the prevention of vomiting. Early esophagoscopy (to the level of first lesion, if present) is useful to identify those patients who do not need hospitalization or treatment. Esophagoscopy and contrast esophagram are useful to define the full extent of esophageal injury, but should be withheld until after the acute phase. Glucocorticoids are probably useful in limiting the extent and severity of esophageal stricture, the most frequent and significant long-term sequela. Colon interposition is used in those situations in which dilation of a stricture has been unsuccessful, and may prevent the subsequent development of esophageal carcinoma.

Child, Preschool

Primary structure of the variable regions of two canine immunoglobulin heavy chains.

The complete amino acid sequences of the variable regions of two canine immunoglobulin heavy chains have been determined by automated Edman degradation and found to be strongly homologous to the human VHIII subgroup. The canine sequences were identical with each other at 76 of 113 residue positions. Twenty-three of the 37 differences are located within the four hypervariable regions previously defined by the sequences of several human VHIII proteins. Forty-five of 77 framework residue positions are invariant in the seven human and two canine VHIII proteins which have been completely sequences. The canine proteins are 78% homologous to the framework of the human prototype. Phylogenetically associated residues before the first hypervariable region were confirmed and several potential phylogenetically associated residues were identified between the first and third hypervariable regions. This study represents the first complete amino acid sequences of VH regions of spontaneously occurring, nonhuman homogeneous immunoglobulins. The date demonstrate a high degree of preservation of VHIII structure in another species.

Amino Acid Sequence

The amino-terminal sequence of the VHIII subgroup of pooled porcine IgG.

Pig gamma-chains contain a significant fraction of the unblocked VHIII variable region subgroup. The amino terminal sequence (30 residues) was found to be uniform and more than 90% homologous with the prototype sequence of the human VHIII subgroup. An additional VHIII phylogenetically associated residue, glutamic acid in position 2 was identified in these porcine heavy chains.

Amino Acid Sequence

Phylogenetically associated residues within the VH3 subgroup of several mammalian species. Evidence for a "pauci-gene" basis for antibody diversity.

Immunoglobulin heavy chains from IgG pools of several mammalian species have been subjected to Edman degradation on an automated protein sequencer. The percentage of unblocked vs. blocked heavy chains was estimated from the yield of the invariant valine in the second position. Further analysis of these unblocked polypeptides unequivocally placed them in the V(HIII) subgroup on the basis of homology with known human heavy chain sequences. The mammals studied could be divided into three distinct categories on the basis of the distribution of the V(HIII) subgroup. In several species the V(HIII) subgroup could not be detected while, in others, virtually all of the heavy chains belonged to this subgroup. Several species had intermediate amounts with the level of the V(HIII) subgroup restricted to between 19 and 29% of the total pool. Within experimental error, all members of a given order had a similar V(HIII) subgroup distribution. Further amino acid sequence studies illustrated a high degree of structural homogeneity in the heavy chains of IgG isolated from pooled sera of a number of mammalian species. The very close amino acid sequence homologies of the amino terminal 24 residues of the various pools corroborated conclusions previously obtained using several myeloma proteins from some of these same species. In particular, certain phylogenetically associated residues were identifiable at characteristic positions in the pools in confirmation of their identification in the myeloma proteins. The simplest assumptions would suggest that these findings are more compatible with a pauci-gene than a multi-gene basis for the generation of antibody diversity.

Amino Acid Sequence