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J Oh

Publications and source records attributed to J Oh.

At least 73 records · Page 4Linked to original sources
PubMed1998

Aspects of antigen mimicry revealed by immunization with a peptide mimetic of Cryptococcus neoformans polysaccharide.

We have recently identified peptide mimetics of the Cryptococcus neoformans capsular polysaccharide by screening phage display peptide libraries. 2H1, one of a large family of mAbs against the glucuronoxylomannan fraction (GXM), is highly protective and binds several peptide motifs. This study analyzes the immunologic properties of P601E (SYSWMYE), a peptide from the low affinity motif (W/YXWM/LYE) that has an extended cross-reactivity among anti-GXM mAbs and whose binding correlates with the protective potential of mAbs in experimental infection. P601E is a mimetic, since it competes for GXM binding to 2H1, but not a mimotope, since it does not elicit an anti-GXM response. Sequence analysis of 14 anti-P601E mAbs indicates that anti-P601E mAbs elicited in BALB/c mice have an order of homology with 2H1 of V kappa > J kappa >> V(H) > J(H) > D. Further screening of a peptide library with anti-P601E mAbs isolated peptides having a motif almost identical to the peptide motif selected by 2H1. When these results are compared to the crystal structure of a related peptide in complex with 2H1, there is a clear correlation between the ability to elicit V region components of 2H1 Ab and peptide association with the V region, suggesting that the completeness of the fit in the binding site is an important driving force for mimicry. As a consequence, improving affinity of a mimetic for the Ab binding site seems to be the most logical way to insure that all of the appropriate V region segments are elicited and that useful mimotopes are created.

Amino Acid Sequence↗
PubMed1998

Antibody-mediated modulation of Cryptococcus neoformans infection is dependent on distinct Fc receptor functions and IgG subclasses.

Coupling of an antibody response to effector cells through the Fc region of antibodies is a fundamental objective of effective vaccination. We have explored the role of the Fc receptor system in a murine model of Cryptococcus neoformans protection by infecting mice deleted for the common gamma chain of FcRs. Passive administration of an IgG1 mAb protects FcRgamma+/- mice infected with C. neoformans, but fails to protect FcRgamma-/- mice, indicating that the gamma chain acting through FcgammaRI and/or III is essential for IgG1-mediated protection. In contrast, passive administration of an IgG3 mAb with identical specificity resulted in enhanced pathogenicity in gamma chain-deficient and wild-type mice. In vitro studies with isolated macrophages demonstrate that IgG1-, IgG2a-, and IgG2b-opsonized C. neoformans are not phagocytosed or arrested in their growth in the absence of the FcRgamma chain. In contrast, opsonization of C. neoformans by IgG3 does not require the presence of the gamma chain or of FcRII, and the internalization of IgG3-treated organisms does not arrest fungal growth.

Animals↗
PubMed1998

Possible implication for an indirect interaction between basic fibroblast growth factor and (Na,K)ATPase.

The (Na,K)ATPase is responsible for generating the ionic gradients and membrane potentials by the exchange of intracellular Na+ for K+. It has been recently shown that (Na,K)ATPase is involved in the exocytic pathway of basic fibroblast growth factor (bFGF), although it is not known that bFGF is secreted to the outside of cell through direct interaction with (Na,K)ATPase. To understand the role for (Na,K)ATPase in the secretory pathway of bFGF, we have sought to identify the cytoplasmic domains of the alpha 1 isoform of (Na,K)ATPase interacting with bFGF by yeast two-hybrid system. We have also investigated the interaction between the alpha 2 isoform of (Na,K)ATPase and bFGF to find out whether the interaction is isoform-specific. We found that none of the cytoplasmic domains of (Na,K)ATPase isoforms interacted with bFGF. The result suggests that the interaction between bFGF and (Na,K)ATPase might be indirect, thus requiring other proteins which are involved in the formation of protein complexes for the interaction, although we cannot exclude the possibility that the interaction requires the element of the whole alpha subunit structure that was not present in the isolated alpha subunit cytoplasmic domains.

Blotting, Western↗
PubMed1998

Nucleotide and deduced amino acid sequences of rat myosin binding protein H (MyBP-H).

The complete nucleotide sequence of the cDNA clone encoding rat skeletal muscle myosin-binding protein H (MyBP-H) was determined and amino acid sequence was deduced from the nucleotide sequence (GenBank accession number AF077338). The full-length cDNA of 1782 base pairs(bp) contains a single open reading frame of 1454 bp encoding a rat MyBP-H protein of the predicted molecular mass 52.7 kDa and includes the common consensus 'CA__TG' protein binding motif. The cDNA sequence of rat MyBP-H show 92%, 84% and 41% homology with those of mouse, human and chicken, respectively. The protein contains tandem internal motifs array (-FN III-Ig C2-FN III-Ig C2-) in the C-terminal region which resembles to the immunoglobulin superfamily C2 and fibronectin type III motifs. The amino acid sequence of the C-terminal Ig C2 was highly conserved among MyBPs family and other thick filament binding proteins, suggesting that the C-terminal Ig C2 might play an important role in its function. All proteins belonging to MyBP-H member contains 'RKPS' sequence which is assumed to be cAMP- and cGMP-dependent protein kinase A phosphorylation site. Computer analysis of the primary sequence of rat MyBP-H predicted 11 protein kinase C (PKC) phosphorylation site, 7 casein kinase II (CK2) phosphorylation site and 4 N-myristoylation site.

Amino Acid Sequence↗
PubMed1998

Evaluation and management of men whose radical prostatectomies failed: results of an international survey.

OBJECTIVES: To determine how urologists evaluate and treat men who develop recurrent prostate cancer after radical prostatectomy. METHODS: Surveys were mailed to 4467 American Urological Association members comprising 3205 U.S. and 1262 non-U.S. urologists randomly selected from a total membership of approximately 12,000. One thousand four hundred sixteen were returned and 1050 (760 U.S. and 290 non-U.S.) surveys were evaluable. RESULTS: To evaluate men with an elevated or rising prostate-specific antigen (PSA) level more than 1 year after radical prostatectomy, 98% of respondents use digital rectal examination, 68% use bone scan, 54% use transrectal ultrasound with biopsy, 36% use abdominal or pelvic computed tomography scan, 31% use transrectal ultrasound without biopsy, 25% use prostatic acid phosphatase, 11% use monoclonal antibody scan, and 5% use abdominal or pelvic magnetic resonance imaging. Respondents evaluate men with an elevated or rising PSA within 1 year of radical prostatectomy similarly. To treat documented local recurrence, 81% of respondents recommend radiation therapy, 7% recommend orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonists, 6% recommend observation only, and 5% recommend combined androgen ablation. To treat documented distant recurrence, 50% recommend combined androgen ablation, 42% recommend orchiectomy or LHRH agonists, and 7% recommend observation only. To treat PSA-only recurrence, 54% recommend observation only, 16% recommend combined androgen ablation, 15% recommend orchiectomy or LHRH agonists, and 13% recommend radiation therapy. CONCLUSIONS: The evaluation of men whose radical prostatectomy failed varies among urologists and does not depend on time of recurrence. Radiation therapy is used by most urologists to treat local recurrence. Hormonal manipulation is used by more than 90% of urologists to treat distant recurrence. More than 50% of urologists recommend observation for men with biochemical-only recurrence.

Adult↗
PubMed1998

Evaluation and management of the man who has failed primary curative therapy for prostate cancer.

The recurrence of prostate cancer after potentially curative local therapy is becoming a significant urologic problem. There are few prospective randomized trials, and the optimal diagnostic and treatment strategies for men who fail potentially curative therapy are not known. The experience to date seems to suggest the following as a reasonable approach. A detectable serum PSA level (> or = 0.4 ng/mL) after radical prostatectomy is evidence of residual or recurrent prostate cancer. Men with low- or moderate-grade cancers (Gleason score < 7), with capsular penetration, or with positive surgical margins in whom disease recurs more than 2 years after radical prostatectomy with a PSA doubling time greater than 12 months seem likely to harbor a local recurrence and are the only good candidates for salvage therapy. Unless there is a palpable recurrence, transrectal ultrasound and biopsy are generally not recommended, and CT scanning and bone scintigraphy usually do not provide helpful information. The role of monoclonal antibody scanning is currently investigational. Men with high-grade tumors (Gleason score > or = 7) or with seminal vesicle or lymph node involvement in whom disease recurs within 2 years of radical prostatectomy are most appropriately observed or treated with early hormonal therapy. Men who do not achieve a PSA nadir of 0.5 ng/mL or less within 2 years of radiotherapy are very likely to harbor residual disease. For young healthy men who are willing to accept a substantial risk of impotency, urinary incontinence, and bladder neck contractures, salvage radical prostatectomy is a reasonable option if the preradiation tumor characteristics are acceptable (PSA < 10 ng/mL, Gleason score < or = 6) and if the current PSA is less than 10 ng/mL. Salvage cryotherapy may result in substantial morbidity and should only be offered on an investigational basis. Other men failing radiation may be observed or treated with hormonal therapy. There is seldom a role for repeat biopsy. Because the optimal time to begin hormone therapy is still not known, early or delayed treatment are both reasonable options. Testicular androgen ablation by orchiectomy or LHRH agonists is considered standard therapy. Combined therapy with an antiandrogen does not seem to be beneficial for all patients and should not be routinely used. Sexually active men in whom preservation of potency is important can be offered an investigational regimen such as a 5-alpha-reductase inhibitor combined with an oral antiandrogen or intermittent LHRH agonist therapy. It is hoped that the results of ongoing randomized trials and future research will establish efficient and effective practice guidelines to evaluate and treat men who have failed potentially curative therapy for localized prostate cancer. This remains a very important and controversial topic that will challenge many practicing urologists.

Cryotherapy↗
PubMed1998

Effects of relative humidity and applied force on atomic force microscopy images of the filamentous phage fd.

The filamentous phage fd was studied by both contact- and tapping-mode atomic force microscopy under conditions of controlled variations in relative humidity and changes in the applied tip force. By spin-coating freshly cleaved mica with phage containing solutions having very low salt content followed by rapid humidity control, stable and reliable sample preparation was achieved. The apparent height of the phage varied by about 10-fold with a quadratic dependence on the stabilized relative humidity, extrapolating to 73% of the accepted X-ray diffraction-based height at 0% relative humidity. The variation in measured height with relative humidity largely reconciles previous widely varying atomic force microscopy estimates of this dimension for the filamentous phage. Our finding that contact-mode images of phage are more difficult to analyze than those acquired in tapping mode are consistent with previously published results on other biological specimens such as DNA.

Humidity↗
PubMed1998

Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.

Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles-melanosomes, platelet-dense granules, and lysosomes. As reported elsewhere, we mapped the human HPS gene to chromosome segment 10q23, positionally cloned the gene, and identified three pathologic mutations of the gene, in patients from Puerto Rico, Japan, and Europe. Here, we describe mutation analysis of 44 unrelated Puerto Rican and 24 unrelated non-Puerto Rican HPS patients. A 16-bp frameshift duplication, the result of an apparent founder effect, is nearly ubiquitous among Puerto Rican patients. A frameshift at codon 322 may be the most frequent HPS mutation in Europeans. We also describe six novel HPS mutations: a 5' splice-junction mutation of IVS5, three frameshifts, a nonsense mutation, and a one-codon in-frame deletion. These mutations define an apparent frameshift hot spot at codons 321-322. Overall, however, we detected mutations in the HPS gene in only about half of non-Puerto Rican patients, and we present evidence that suggests locus heterogeneity for HPS.

Albinism, Oculocutaneous↗
PubMed1998

Isotype switching increases efficacy of antibody protection against Cryptococcus neoformans infection in mice.

The isotype and epitope specificities of antibodies both contribute to the efficacy of antibodies that mediate immunity to Cryptococcus neoformans, but the relationship between these properties is only partially understood. In this study, we analyzed the efficacy of protection of two sets of immunoglobulin G (IgG) isotype switch variants from two IgG3 monoclonal antibodies (MAbs) which are either not protective or disease enhancing, depending on the mouse model used. The two IgG3 MAbs 3E5 and 4H3 have different epitope specificities. Protection experiments were done with A/JCr mice infected intravenously with C. neoformans and administered with 3E5 IgG3 and its IgG1, IgG2a, and IgG2b switch variants. These experiments revealed that IgG1, IgG2b, and IgG2a were each more effective than IgG3. For 4H3 IgG3 and its IgG1 and IgG2b switch variants, the relative efficacy was IgG2b > IgG1 >> IgG3. The combination of 3E5 IgG3 and 4H3 IgG3 was more deleterious than either IgG3 alone. All IgG isotypes were opsonic for mouse bronchoalveolar cells, with the relative efficacy being IgG2b > IgG2a > IgG1 > IgG3. These results (i) confirm that a nonprotective IgG3 MAb can be converted to a protective MAb by isotype switching, (ii) indicate that the efficacy of protection of an IgG1 MAb can be increased by isotype switching to another subclass, (iii) show that protective and nonprotective IgG MAbs are opsonic, and (iv) provide additional evidence for the concept that the efficacy of the antibody response to C. neoformans is dependent on the type of MAb elicited.

Animals↗
PubMed1998

Molecular basis for effects of carcinogenic heavy metals on inducible gene expression.

Certain forms of the heavy metals arsenic and chromium are considered human carcinogens, although they are believed to act through very different mechanisms. Chromium(VI) is believed to act as a classic and mutagenic agent, and DNA/chromatin appears to be the principal target for its effects. In contrast, arsenic(III) is considered nongenotoxic, but is able to target specific cellular proteins, principally through sulfhydryl interactions. We had previously shown that various genotoxic chemical carcinogens, including chromium (VI), preferentially altered expression of several inducible genes but had little or no effect on constitutive gene expression. We were therefore interested in whether these carcinogenic heavy metals might target specific but distinct sites within cells, leading to alterations in gene expression that might contribute to the carcinogenic process. Arsenic(III) and chromium(VI) each significantly altered both basal and hormone-inducible expression of a model inducible gene, phosphoenolpyruvate carboxykinase (PEPCK), at nonovertly toxic doses in the chick embryo in vivo and rat hepatoma H411E cells in culture. We have recently developed two parallel cell culture approaches for examining the molecular basis for these effects. First, we are examining the effects of heavy metals on expression and activation of specific transcription factors known to be involved in regulation of susceptible inducible genes, and have recently observed significant but different effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding. Second, we have developed cell lines with stably integrated PEPCK promoter-luciferase reporter gene constructs to examine effects of heavy metals on promoter function, and have also recently seen profound effects induced by both chromium(VI) and arsenic(III) in this system. These model systems should enable us to be able to identify the critical cis (DNA) and trans (protein) cellular targets of heavy metal exposure leading to alterations in expression of specific susceptible genes. It is anticipated that such information will provide valuable insight into the mechanistic basis for these effects as well as provide sensitive molecular biomarkers for evaluating human exposure.

Animals↗
PubMed1998

A rare case of patent ductus arteriosus in a dog with glomerular mesangiolysis.

Rare case of patent ductus arteriosus (PDA) was observed in a 2-year and 9 month-old Miniature Dachshund which had been diagnosed as severe cardiac failure. Pulmonary artery from the right ventricle connected to dilated ductus arteriosus, and pulmonary artery-ductus arteriosus-descending aorta formed a continuous duct, which seemed to be the main route of bloodstream. Ascending aorta from the left ventricle was hypoplastic, and connected to the dilated ductus arteriosus. Glomerular mesangiolysis due to heart failure was also observed in the kidney.

Animals↗
PubMed1997

T cells cooperate with passive antibody to modify Cryptococcus neoformans infection in mice.

Cryptococcus neoformans is an encapsulated fungus that is a major cause of meningitis in patients with AIDS. In immunocompetent mice, administration of IgG1 mAb protects against cryptococcal infection, whereas administration of IgG3 is not protective and can accelerate the infection. In beige mice with impaired natural killer cell function, the effects of IgG1 and IgG3 are similar to those observed in immunocompetent mice, suggesting that natural killer cells are not crucial for antibody-mediated modulation of cryptococcal infection. In mice lacking CD4+ T cells, IgG1 is not protective and IgG3 accelerates infection, indicating that CD4+ T cells are required for antibody-mediated protection. In mice lacking CD8+ T cells, both IgG1 and IgG3 antibodies prolong survival, indicating that acceleration of the disease process by IgG3 involves CD8+ T cells. Both IgG1-mediated protection and IgG3-mediated acceleration of infection require interferon gamma. These results reveal a functional dependence of passively administered antibody on cellular immunity in cryptococcal infection in mice and have implications for antibody-based therapies in humans in the setting of CD4+ lymphopenia.

Animals↗
PubMed1997

Mouse pale ear (ep) is homologous to human Hermansky-Pudlak syndrome and contains a rare 'AT-AC' intron.

Hermansky-Pudlak syndrome (HPS) is a rare, often fatal, autosomal recessive disorder in which albinism, bleeding and lysosomal storage are associated with defects of diverse cytoplasmic organelles, including melanosomes, platelet dense granules and lysosomes. Similar multi-organellar defects occur in the Chediak-Higashi syndrome (CHS), as well as in a large number of different mouse mutants. The HPS gene is located in 10q23, and two genetically distinct mouse loci, pale ear (ep) and ruby-eye (ru), both with mutant phenotypes similar to human HPS, map close together in the homologous region of murine chromosome 19, suggesting that one of these loci might be homologous to human HPS. We recently identified the human HPS gene, which encodes a novel ubiquitously-expressed transmembrane protein of unknown function. Here, we describe characterization of the mouse Hps cDNA and genomic locus, and identification of pathologic Hps gene mutations in ep but not in ru mice, establishing mouse pale ear as an animal model for human HPS. The phenotype of homozygous ep mutant mice encompasses those of both HPS and CHS, suggesting that these disorders may be closely related. In addition, the mouse and human HPS genes both contain a rare 'AT-AC' intron, and comparison of the sequences of this intron in the mouse and human genes identified conserved sequences that suggest a possible role for pre-mRNA secondary structure in excision of this rare class of introns.

Albinism, Oculocutaneous↗
PubMed1997

Organization and nucleotide sequence of the human Hermansky-Pudlak syndrome (HPS) gene.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, bleeding tendency, and lysosomal ceroid storage disease, associated with defects of multiple cytoplasmic organelles-melanosomes, platelet-dense granules, and lysosomes. HPS is frequently fatal and is the most common single-gene disorder in Puerto Rico. We previously characterized the human HPS cDNA and identified pathologic mutations in the gene in patients with HPS. The HPS protein is a novel apparent transmembrane polypeptide that seems to be crucial for normal organellar development. Here we describe the structural organization, nucleotide sequence, and polymorphisms of the human HPS gene. The gene consists of 20 exons spanning about 30.5 kb in chromosome segment 10q23.1-q23.3. One of the intervening sequences is a member of the novel, very rare class of so-called "AT-AC" introns, defined by highly atypical 5' and 3' splice site and branch site consensus sequences that provide novel targets for possible pathologic gene mutations. This information provides the basis for molecular analyses of patients with HPS and will greatly facilitate diagnosis and carrier detection of this severe disorder.

Albinism, Oculocutaneous↗