Richard Linsk - Academia.edu (original) (raw)
Papers by Richard Linsk
Genetics, 1994
A newly identified locus in Drosophila melanogaster, Mosaic suppressor (Msu), is described. This ... more A newly identified locus in Drosophila melanogaster, Mosaic suppressor (Msu), is described. This gene modifies the expression of white-apricot (wa), which is a copia retrotransposon-induced allele of the white gene. In addition to suppressing wa in a mosaic fashion, this mutation suppresses or enhances the expression of several other retrotransposon induced white alleles. Mutations in Msu alter copia transcript abundance and may regulate the expression of several other retrotransposons. While each of the two Msu isolates is homozygous lethal, heteroallelic escapers occur at a low frequency. These escapers act not only as strong suppressors of wa, but also as a recessive enhancer of synaptic-dependent gene expression at white. The mutation described here suggests a connection between the regulation of specific transcriptional units such as retrotransposons and more global synapsis dependent regulatory effects.
Thesis (Ph. D. in Genetics)--University of California, Berkeley, May 1988. Includes bibliographic... more Thesis (Ph. D. in Genetics)--University of California, Berkeley, May 1988. Includes bibliographical references (leaves 115-134).
Clinical Pediatrics, 2004
We surveyed pediatricians (PEDs), family physicians (FPs), otolaryngologists (ENTs), and emergenc... more We surveyed pediatricians (PEDs), family physicians (FPs), otolaryngologists (ENTs), and emergency physicians (ERs) from across Michigan (100 each), as well as 30 nationally recognized experts about their clinical approach to acute otitis media (AOM). The overall response rate was 52%. There was substantial variation within each group with respect to diagnostic criteria and clinical decision-making, but no significant differences among groups. The 63% of respondents who considered symptoms among their diagnostic criteria for AOM were 3.8-fold more likely to defer therapy for an asymptomatic toddler with a bulging, red, immobile tympanic membrane (TM) (95% Confidence Interval (CI) 1.53, 9.74), but 24% of respondents stated that they would prescribe oral antibiotics for a symptomatic child with a red TM, even in the absence of a middle ear effusion. These data suggest that diagnostic criteria are a major factor determining whether clinicians prescribe antibiotics to a particular patient.
Class I and class II major histocompatibility (MHC) antigens are polymorphic cell surface glycopr... more Class I and class II major histocompatibility (MHC) antigens are polymorphic cell surface glycoproteins which play central roles in controlling target cell recognition by antigen specific cytotoxic and helper T cells. The class I molecules are expressed ubiquitously and, in general, are involved in the presentation of intracellular and cell surface viral antigens to cytotoxic T-Iymphocytes (CTLs). On the other hand, class II molecules are expressed primarily on antigen presenting cells such as macrophages and B cells, where they are involved in the presentation of phagocytized or internalized foreign antigens to helper T cells (Zinkernagel and Doherty 1979; Schwartz 1984). As a rule, T cells exhibit an obligatory requirement of corecognition of antigen and MHC antigen of their own haplotype or "restriction element." Therefore, T cell recognition is said to be "MHC restricted." Another intriguing feature of T cell recognition is the phenomenon of all 0 react ivity...
MHC + X, 1988
Class I and class II major histocompatibility (MHC) antigens are polymorphic cell surface glycopr... more Class I and class II major histocompatibility (MHC) antigens are polymorphic cell surface glycoproteins which play central roles in controlling target cell recognition by antigen specific cytotoxic and helper T cells. The class I molecules are expressed ubiquitously and, in general, are involved in the presentation of intracellular and cell surface viral antigens to cytotoxic T-lymphocytes (CTLs). On the other hand, class II molecules are expressed primarily on antigen presenting cells such as macrophages and B cells, where they are involved in the presentation of phagocytized or internalized foreign antigens to helper T cells (Zinkernagel and Doherty 1979; Schwartz 1984). As a rule, T cells exhibit an obligatory requirement of corecognition of antigen and MHC antigen of their own haplotype or “restriction element.” Therefore, T cell recognition is said to be “MHC restricted.”
Science, 1985
The H-2 Antigens of the Major Histocompatibility Complex The major histocompatibility complex (MH... more The H-2 Antigens of the Major Histocompatibility Complex The major histocompatibility complex (MHC) of the mouse consists of three classes of genes that encode cell surface and secreted products involved in immune regulation and function (1). Within the MHC, the class I genes represent a large multigene family of distinct, but related, sequences encoding several types of products. These products include the transplantation antigens, which (CTL's) against virally infected or neoplastic cells (Fig. 1). Although the precise molecular basis of T-cell recognition remains unknown, CTL function exhibits an absolute requirement for associated recognition between foreign antigens and self MHC components (4-6). As the products of specific class I genes are required for the restricted recognition of different viral antigens, the H-2 molecules are often referred to as restriction or control elements for CTL function. In addition, some CTL's can recognize Summary. Recent advances in tumor immunology suggest that the expression of the histocompatibility antigens, encoded by the major histocompatibility complex, is important in controlling the metastatic growth of certain murine tumors. The anomalous expression of histocompatibility antigens in many neoplasms appears to be associated with the ability of these cells to evade the immune system and progress to metastasis. This review examines some of the underlying molecular and immunobiological interactions that might determine the metastatic outcome of cellular transformation.
European Journal of Immunogenetics, 1986
Many tumours are highly immunogenic when transplanted into histocompatible animals and are, there... more Many tumours are highly immunogenic when transplanted into histocompatible animals and are, therefore, rejected by immunocompetent hosts (Doherty et al., 1984; Goodenow et al., 1985). Although the biochemical nature of the products responsible for tumour
Genetics, 1994
We are interested in identifying single gene mutations that are involved in trans-acting dosage r... more We are interested in identifying single gene mutations that are involved in trans-acting dosage regulation in order to understand further the role of such genes in aneuploid syndromes, various types of dosage compensation as well as in regulatory mechanisms. The Lighten up (Lip) gene in Drosophila melanogaster was identified in a mutagenic screen to detect dominant second site modifiers of white-blood (wbl), a retrotransposon induced allele of the white eye color locus. Lip specifically enhances the phenotype of wbl as well as a subset of other retroelement insertion alleles of white, including the copia-induced allele, white-apricot (wa), and six alleles caused by insertion of I elements. We isolated six alleles of Lip which are all recessive lethal, although phenotypically additive heteroallelic escapers were recovered in some combinations. Lip also suppresses position effect variegation, indicating that it may have a role in chromatin configuration. Additionally, Lip modifies the...
Proceedings of the National Academy of Sciences, 1988
We have isolated cytotoxic T lymphocytes (CTL) preferentially reactive with the alpha 1 external ... more We have isolated cytotoxic T lymphocytes (CTL) preferentially reactive with the alpha 1 external domain of the H-2Ld antigen by selecting for T cells capable of recognizing a variant major histocompatibility complex (MHC) class I antigen sharing alpha 1 sequences with H-2Ld. Using these CTL, we demonstrate that a synthetic alpha 1 peptide corresponding to one of the helices derived from the H-2Ld molecule can be presented by a class I restriction element to reconstitute a CTL determinant borne by intact H-2Ld. Moreover, several other H-2L-reactive CTL generated independently were also able to recognize H-2Ld either as an intact alloantigen or as a peptide in conjunction with appropriate class I restriction elements. These data demonstrate that an H-2 peptide can reconstitute a CTL target structure and suggest that some alloreactive T cells in fact might be directed against allogeneic class I peptides in the context of a class I framework.
Contemporary pediatrics, 1999
Resistance is only one reason acute otitis media may fail to respond to a first course of amoxici... more Resistance is only one reason acute otitis media may fail to respond to a first course of amoxicillin. In deciding what to do next, you'll need to take the other possibilities into account as well.
Journal of Experimental Medicine, 1989
Previously, we cloned and sequenced the three novel MHC class I genes expressed by the C3H UV fib... more Previously, we cloned and sequenced the three novel MHC class I genes expressed by the C3H UV fibrosarcoma, 1591. We have extended the analysis of the polymorphic nature of these genes relative to the C3H strain. Scattered nucleotide differences among the tumor genes as compared with the C3H H-2 and Qa sequences make it highly unlikely that the novel tumor genes were generated by recombination between endogenous C3H sequences. Given that two of the tumor clones, A149 and A166, are remarkably similar in amino acid and DNA sequence to H-2Lq and H-2Dq, respectively, we also examined the 1591 RP2 and GUS loci for evidence of polymorphism. Compared with C3H and B10.AKM, 1591 appears to be heterozygous at each of these loci, consistent with an H-2q origin for the two novel 1591 class I genes. Interestingly, the third tumor gene, designated A216, shares certain characteristics with the H-2Ks antigen, reminiscent of the naturally occurring combination of H-2Ks, H-2Dq, and H-2Lq antigens fou...
Journal of Experimental Medicine, 1986
The UV-induced, C3H fibrosarcoma, 1591, expresses at least three unique MHC class I antigens not ... more The UV-induced, C3H fibrosarcoma, 1591, expresses at least three unique MHC class I antigens not found on normal C3H tissue. Here we report the complete DNA sequence of the three novel class I genes encoding these molecules, and describe in detail the recognition of the individual products by tumor-reactive and allospecific CTL. Remarkably, although C3H does not appear to express H-2L locus information, this C3H tumor expresses two distinct antigens, termed A149 and A166, which are extremely homologous to each other and to the H-2Ld antigen from BALB/c. The gene encoding the third novel class I antigen from 1591, A216, is quite homologous to H-2Kk) throughout its 3' end. Since all three of these genes account for polymorphic restriction fragments not found in C3H, it is likely that they were derived by recombination from the endogenous class I genes of C3H. The DNA sequence homology of A149, A166, and H-2Ld is especially significant given the functional conservation observed bet...
Genetics, 1994
Copyright 0 1994 by the Genetics Society of America ... Weakener of white (Wow), a Gene That Modi... more Copyright 0 1994 by the Genetics Society of America ... Weakener of white (Wow), a Gene That Modifies the Expression of the white Eye Color Locus and That Suppresses Position Effect Variegation in Drosophila melanogaster ... James A. Birchler,**f Utpal Bhadra," Leonard Rabinow,+.' ...
Genetics, 1994
A newly identified locus in Drosophila melanogaster, Mosaic suppressor (Msu), is described. This ... more A newly identified locus in Drosophila melanogaster, Mosaic suppressor (Msu), is described. This gene modifies the expression of white-apricot (wa), which is a copia retrotransposon-induced allele of the white gene. In addition to suppressing wa in a mosaic fashion, this mutation suppresses or enhances the expression of several other retrotransposon induced white alleles. Mutations in Msu alter copia transcript abundance and may regulate the expression of several other retrotransposons. While each of the two Msu isolates is homozygous lethal, heteroallelic escapers occur at a low frequency. These escapers act not only as strong suppressors of wa, but also as a recessive enhancer of synaptic-dependent gene expression at white. The mutation described here suggests a connection between the regulation of specific transcriptional units such as retrotransposons and more global synapsis dependent regulatory effects.
Thesis (Ph. D. in Genetics)--University of California, Berkeley, May 1988. Includes bibliographic... more Thesis (Ph. D. in Genetics)--University of California, Berkeley, May 1988. Includes bibliographical references (leaves 115-134).
Clinical Pediatrics, 2004
We surveyed pediatricians (PEDs), family physicians (FPs), otolaryngologists (ENTs), and emergenc... more We surveyed pediatricians (PEDs), family physicians (FPs), otolaryngologists (ENTs), and emergency physicians (ERs) from across Michigan (100 each), as well as 30 nationally recognized experts about their clinical approach to acute otitis media (AOM). The overall response rate was 52%. There was substantial variation within each group with respect to diagnostic criteria and clinical decision-making, but no significant differences among groups. The 63% of respondents who considered symptoms among their diagnostic criteria for AOM were 3.8-fold more likely to defer therapy for an asymptomatic toddler with a bulging, red, immobile tympanic membrane (TM) (95% Confidence Interval (CI) 1.53, 9.74), but 24% of respondents stated that they would prescribe oral antibiotics for a symptomatic child with a red TM, even in the absence of a middle ear effusion. These data suggest that diagnostic criteria are a major factor determining whether clinicians prescribe antibiotics to a particular patient.
Class I and class II major histocompatibility (MHC) antigens are polymorphic cell surface glycopr... more Class I and class II major histocompatibility (MHC) antigens are polymorphic cell surface glycoproteins which play central roles in controlling target cell recognition by antigen specific cytotoxic and helper T cells. The class I molecules are expressed ubiquitously and, in general, are involved in the presentation of intracellular and cell surface viral antigens to cytotoxic T-Iymphocytes (CTLs). On the other hand, class II molecules are expressed primarily on antigen presenting cells such as macrophages and B cells, where they are involved in the presentation of phagocytized or internalized foreign antigens to helper T cells (Zinkernagel and Doherty 1979; Schwartz 1984). As a rule, T cells exhibit an obligatory requirement of corecognition of antigen and MHC antigen of their own haplotype or "restriction element." Therefore, T cell recognition is said to be "MHC restricted." Another intriguing feature of T cell recognition is the phenomenon of all 0 react ivity...
MHC + X, 1988
Class I and class II major histocompatibility (MHC) antigens are polymorphic cell surface glycopr... more Class I and class II major histocompatibility (MHC) antigens are polymorphic cell surface glycoproteins which play central roles in controlling target cell recognition by antigen specific cytotoxic and helper T cells. The class I molecules are expressed ubiquitously and, in general, are involved in the presentation of intracellular and cell surface viral antigens to cytotoxic T-lymphocytes (CTLs). On the other hand, class II molecules are expressed primarily on antigen presenting cells such as macrophages and B cells, where they are involved in the presentation of phagocytized or internalized foreign antigens to helper T cells (Zinkernagel and Doherty 1979; Schwartz 1984). As a rule, T cells exhibit an obligatory requirement of corecognition of antigen and MHC antigen of their own haplotype or “restriction element.” Therefore, T cell recognition is said to be “MHC restricted.”
Science, 1985
The H-2 Antigens of the Major Histocompatibility Complex The major histocompatibility complex (MH... more The H-2 Antigens of the Major Histocompatibility Complex The major histocompatibility complex (MHC) of the mouse consists of three classes of genes that encode cell surface and secreted products involved in immune regulation and function (1). Within the MHC, the class I genes represent a large multigene family of distinct, but related, sequences encoding several types of products. These products include the transplantation antigens, which (CTL's) against virally infected or neoplastic cells (Fig. 1). Although the precise molecular basis of T-cell recognition remains unknown, CTL function exhibits an absolute requirement for associated recognition between foreign antigens and self MHC components (4-6). As the products of specific class I genes are required for the restricted recognition of different viral antigens, the H-2 molecules are often referred to as restriction or control elements for CTL function. In addition, some CTL's can recognize Summary. Recent advances in tumor immunology suggest that the expression of the histocompatibility antigens, encoded by the major histocompatibility complex, is important in controlling the metastatic growth of certain murine tumors. The anomalous expression of histocompatibility antigens in many neoplasms appears to be associated with the ability of these cells to evade the immune system and progress to metastasis. This review examines some of the underlying molecular and immunobiological interactions that might determine the metastatic outcome of cellular transformation.
European Journal of Immunogenetics, 1986
Many tumours are highly immunogenic when transplanted into histocompatible animals and are, there... more Many tumours are highly immunogenic when transplanted into histocompatible animals and are, therefore, rejected by immunocompetent hosts (Doherty et al., 1984; Goodenow et al., 1985). Although the biochemical nature of the products responsible for tumour
Genetics, 1994
We are interested in identifying single gene mutations that are involved in trans-acting dosage r... more We are interested in identifying single gene mutations that are involved in trans-acting dosage regulation in order to understand further the role of such genes in aneuploid syndromes, various types of dosage compensation as well as in regulatory mechanisms. The Lighten up (Lip) gene in Drosophila melanogaster was identified in a mutagenic screen to detect dominant second site modifiers of white-blood (wbl), a retrotransposon induced allele of the white eye color locus. Lip specifically enhances the phenotype of wbl as well as a subset of other retroelement insertion alleles of white, including the copia-induced allele, white-apricot (wa), and six alleles caused by insertion of I elements. We isolated six alleles of Lip which are all recessive lethal, although phenotypically additive heteroallelic escapers were recovered in some combinations. Lip also suppresses position effect variegation, indicating that it may have a role in chromatin configuration. Additionally, Lip modifies the...
Proceedings of the National Academy of Sciences, 1988
We have isolated cytotoxic T lymphocytes (CTL) preferentially reactive with the alpha 1 external ... more We have isolated cytotoxic T lymphocytes (CTL) preferentially reactive with the alpha 1 external domain of the H-2Ld antigen by selecting for T cells capable of recognizing a variant major histocompatibility complex (MHC) class I antigen sharing alpha 1 sequences with H-2Ld. Using these CTL, we demonstrate that a synthetic alpha 1 peptide corresponding to one of the helices derived from the H-2Ld molecule can be presented by a class I restriction element to reconstitute a CTL determinant borne by intact H-2Ld. Moreover, several other H-2L-reactive CTL generated independently were also able to recognize H-2Ld either as an intact alloantigen or as a peptide in conjunction with appropriate class I restriction elements. These data demonstrate that an H-2 peptide can reconstitute a CTL target structure and suggest that some alloreactive T cells in fact might be directed against allogeneic class I peptides in the context of a class I framework.
Contemporary pediatrics, 1999
Resistance is only one reason acute otitis media may fail to respond to a first course of amoxici... more Resistance is only one reason acute otitis media may fail to respond to a first course of amoxicillin. In deciding what to do next, you'll need to take the other possibilities into account as well.
Journal of Experimental Medicine, 1989
Previously, we cloned and sequenced the three novel MHC class I genes expressed by the C3H UV fib... more Previously, we cloned and sequenced the three novel MHC class I genes expressed by the C3H UV fibrosarcoma, 1591. We have extended the analysis of the polymorphic nature of these genes relative to the C3H strain. Scattered nucleotide differences among the tumor genes as compared with the C3H H-2 and Qa sequences make it highly unlikely that the novel tumor genes were generated by recombination between endogenous C3H sequences. Given that two of the tumor clones, A149 and A166, are remarkably similar in amino acid and DNA sequence to H-2Lq and H-2Dq, respectively, we also examined the 1591 RP2 and GUS loci for evidence of polymorphism. Compared with C3H and B10.AKM, 1591 appears to be heterozygous at each of these loci, consistent with an H-2q origin for the two novel 1591 class I genes. Interestingly, the third tumor gene, designated A216, shares certain characteristics with the H-2Ks antigen, reminiscent of the naturally occurring combination of H-2Ks, H-2Dq, and H-2Lq antigens fou...
Journal of Experimental Medicine, 1986
The UV-induced, C3H fibrosarcoma, 1591, expresses at least three unique MHC class I antigens not ... more The UV-induced, C3H fibrosarcoma, 1591, expresses at least three unique MHC class I antigens not found on normal C3H tissue. Here we report the complete DNA sequence of the three novel class I genes encoding these molecules, and describe in detail the recognition of the individual products by tumor-reactive and allospecific CTL. Remarkably, although C3H does not appear to express H-2L locus information, this C3H tumor expresses two distinct antigens, termed A149 and A166, which are extremely homologous to each other and to the H-2Ld antigen from BALB/c. The gene encoding the third novel class I antigen from 1591, A216, is quite homologous to H-2Kk) throughout its 3' end. Since all three of these genes account for polymorphic restriction fragments not found in C3H, it is likely that they were derived by recombination from the endogenous class I genes of C3H. The DNA sequence homology of A149, A166, and H-2Ld is especially significant given the functional conservation observed bet...
Genetics, 1994
Copyright 0 1994 by the Genetics Society of America ... Weakener of white (Wow), a Gene That Modi... more Copyright 0 1994 by the Genetics Society of America ... Weakener of white (Wow), a Gene That Modifies the Expression of the white Eye Color Locus and That Suppresses Position Effect Variegation in Drosophila melanogaster ... James A. Birchler,**f Utpal Bhadra," Leonard Rabinow,+.' ...