Absence Of gM Research Articles

Interactive Effects of HLA and GM Alleles on the Development of Alzheimer Disease.

ObjectiveWe investigated whether particular immunoglobulin GM (γ marker) alleles—individually or epistatically with a known human leukocyte antigen (HLA) risk allele—were associated with the development of Alzheimer disease (AD).MethodsUsing a prospective cohort study design, we genotyped DNA samples from 209 African American (AA) and 638 European American (EA) participants for IgG1 (GM 3 and GM 17), IgG2 (GM 23+ and GM 23−), and HLA-DRB1 rs9271192 (A/C) alleles by TaqMan and rhAMP genotyping assays.ResultsIn EA subjects, none of the GM or HLA alleles—individually or epistatically—were associated with time to development of AD. In AA subjects, GM and HLA alleles individually were not associated with time to development of AD. However, there was a significant interaction: In the presence of GM 3 (i.e., GM 3/3 and GM 3/17 subjects), the presence of the HLA-C allele was associated with a 4-fold increase in the likelihood of developing AD compared with its absence (hazard ratio [HR] 4.17, 95% CI, 1.28–13.58). In the absence of GM 3 (GM 17/17 subjects), however, the presence of the HLA-C allele was not associated with time to development of AD (HR 1.10, 95% CI, 0.50–2.41).ConclusionsThese results show that particular GM and HLA alleles epistatically contribute to the development of AD.

Herpes Simplex Virus 1 Glycoprotein M and the Membrane-Associated Protein UL11 Are Required for Virus-Induced Cell Fusion and Efficient Virus Entry

Herpes simplex virus 1 (HSV-1) facilitates virus entry into cells and cell-to-cell spread by mediating fusion of the viral envelope with cellular membranes and fusion of adjacent cellular membranes. Although virus strains isolated from herpetic lesions cause limited cell fusion in cell culture, clinical herpetic lesions typically contain large syncytia, underscoring the importance of cell-to-cell fusion in virus spread in infected tissues. Certain mutations in glycoprotein B (gB), gK, UL20, and other viral genes drastically enhance virus-induced cell fusion in vitro and in vivo. Recent work has suggested that gB is the sole fusogenic glycoprotein, regulated by interactions with the viral glycoproteins gD, gH/gL, and gK, membrane protein UL20, and cellular receptors. Recombinant viruses were constructed to abolish either gM or UL11 expression in the presence of strong syncytial mutations in either gB or gK. Virus-induced cell fusion caused by deletion of the carboxyl-terminal 28 amino acids of gB or the dominant syncytial mutation in gK (Ala to Val at amino acid 40) was drastically reduced in the absence of gM. Similarly, syncytial mutations in either gB or gK did not cause cell fusion in the absence of UL11. Neither the gM nor UL11 gene deletion substantially affected gB, gC, gD, gE, and gH glycoprotein synthesis and expression on infected cell surfaces. Two-way immunoprecipitation experiments revealed that the membrane protein UL20, which is found as a protein complex with gK, interacted with gM while gM did not interact with other viral glycoproteins. Viruses produced in the absence of gM or UL11 entered into cells more slowly than their parental wild-type virus strain. Collectively, these results indicate that gM and UL11 are required for efficient membrane fusion events during virus entry and virus spread.

Measurement of colony-stimulating factors in synovial fluid: potential clinical value

In this study, 100 synovial fluid (SF) samples from patients with a variety of arthritides were assayed for levels of colony-stimulating factors (CSFs) using a human bone-marrow bioassay and enzyme immunoassays for granulocyte (G-) and granulocyte-macrophage (GM-) CSFs. GM-CSF was found more frequently in samples from rheumatoid arthritis (RA) subjects (49%) than in non-RA samples (29%). Absence of GM- but not G- or bioassay CSFs characterised samples from subjects with psoriatic arthritis and ankylosing spondylitis (n = 14). There was strong evidence of an antagonistic relationship between levels of G- and GM-CSFs in samples from RA patients, an effect independent of drug treatment. However, treatment with non-steroidal anti-inflammatory agents (NSAIDs) may affect reported CSF concentrations: G-CSF levels were significantly lower in samples from subjects not taking NSAIDs. These results suggest that SF-CSF estimations using commercially available assays could provide useful diagnostic clues for clinicians, but careful interpretation is warranted particularly in patients on long-term NSAID treatment.

Effect of recombinant granulocyte-macrophage colony-stimulating factor on murine thrombocytopoiesis in vitro and in vivo

To investigate the effect of recombinant granulocyte-macrophage colony- stimulating factor (rGM-CSF) on murine megakaryocytopoiesis in vitro, the factor was added to both serum-free colony assays and liquid marrow cultures. GM-CSF had a significant megakaryocytic colony-stimulating activity. After 2 hours of preincubation with and without 10 ng/mL rGM- CSF, the percentage of megakaryocyte colony-forming cell (CFU-MK) in DNA synthesis was determined by tritiated-thymidine suicide using colony growth. The reduction of CFU-MK colony numbers in marrow culture was 47.5% +/- 9.9%, 20.9% +/- 5.2% (control), respectively, indicating that the factor affected cell cycle at CFU-MK levels. When acetylcholinesterase (AchE) production was measured fluorometrically after 4 days of liquid culture, rGM-CSF elicited an increase in AchE activity in a dose-dependent fashion. To determine if the hematopoietin acts directly on megakaryocytic differentiation, 2 ng/mL rGM-CSF was added to serum-free cultures of 295 single megakaryocytes isolated from CFU-MK colonies. An increase in size was observed in 65% of cells initially 10 to 20 microns in diameter, 71% of cells 20 to 30 microns, and 40% of cells greater than 30 microns. Conversely, in absence of GM- CSF, 17%, 31%, and 10% of cells in each group increased in diameter. These data suggest that rGM-CSF promotes murine megakaryocytopoiesis in vitro and that the response to the factor is direct. To determine if the factor influences megakaryocytic/thrombocytic lineage in vivo, 1 and 5 micrograms of rGM-CSF were administered intraperitoneally every 12 hours for 6 consecutive days. Although a two- to three-fold increase in peripheral granulocytes was observed, neither megakaryocytic progenitor cells or platelets changed. Histologic analysis of bone marrow megakaryocytes showed no increase in size and number. The in vivo studies demonstrated no effect of GM-CSF on thrombocytopoiesis. The discrepancies between the in vitro and in vivo effects of GM-CSF require additional investigations.

Interpretation of Gm Testing Results: Two Case Histories

Two cases in which bloodstains and seminal stain evidence were important were subjected to the identification of Gm antigenic determinants. In the first case, the identification of the seminal stain showed the absence of Gm 1 and 12 determinants and the presence of Gm 4. The interpretation of these results would on the surface suggest that the seminal evidence came from one of two suspects. However, since the absence of Gm 12, which occurs on the immunoglobulin G (IgG) 3 subclass, was not confirmed by the demonstration of another IgG 3 subclass Gm antigenic determinant this result was inconclusive. In the second case, bloodstain and seminal fluid evidence showed that seminal fluid identified on the victim's nightgown had Gm antigenic determinants consistent with those of the suspect and also that blood on the suspect's underpants had Gm antigenic determinants consistent with the deceased's blood. The results of these two cases are interpreted with regard to the Gm results obtained.

Immunoglobulin allotypes in peoples from five villages in Nepal

Serum samples from people living in three villages (Simikot, Thymkyn and Yakba) in the Karnali River basin in extreme northwest Nepal and from people living in two villages (Dangrizong and Phalag) in the upper Kali Gandaki River basin in central Nepal were tested for the immunoglobulin allotypes Gm (1,2,3,5,6,10,11,13,14,17,21,24,26) and Inv(Km)(1). The people from one of the villages (Simikot) are Caucasoid in appearance and have cultural, linguistic and religious ties to southern Nepal and India. Those from the four other villages are Mongoloid in appearance and have cultural, linguistic and religious ties to Tibet. The Gm phenotype and haplotype arrays and Inv1 frequency for the samples from Simikot were, as expected, typically Caucasoid. The samples from Thymkyn and Yakba, on the other hand showed no evidence of being from Mongoloid and not Caucasoid individuals, except for the absence of Gm(3,5,10,11,13,14,26) samples. Their phenotypes could be explained by postulating either the Gm3,5,10,11,13,14,26 haplotype found among Caucasoids or the Gm1,3,5,10,11,13,14,26 haplotype found among Mongoloids. The latter is assumed to be present, because of the Mongoloid appearance of the donors of the samples. Larger numbers of samples, preferably from families, are needed to decide which of these alternatives is correct. The Gm haplotype and Inv1 frequencies of the samples from people in Dangrizong and Phalag villages are typically Mongoloid and significantly different from those for the samples from people in Thymkyn and Yakba. The frequencies for samples within the pairs of villages were the same. Whether these data indicate a cline or genetic drift can be determined on the basis of the comparison of data for samples from populations residing between the locations from which the samples were drawn for this study with samples from the two regions already studied. Larger numbers of samples from the two regions already studied are desirable and all samples should be analysed for additional polymorphisms.

Gm factors in non-human primates.

Summary. Eighteen different primate species have been typed for Gm factors present at the human γ2b and γ2c loci. Gm factors are absent in lower primates. The Gm factors, associated with γ2c molecules, namely, Gm(s), (c5), (b0) evolve first in the Cer‐copithecoidea species. Gm(z) occurs together with Gm(a) on human γ2b molecules, but in baboon sera Gm(z) occurs in the absence of Gm(a). The simultaneous occurrence of Gm(a) and (z) in the same sera is established in Hominoidea. Gm(b3) is present only in gorillas, orangutans, and chimpanzees, while Gm(b4) and (c3) was detected in chimpanzees. Polymorphism for the factors studied exists only in orangutans and chimpanzees. The data show a close correlation between taxonomic classification and the evolution of Gm factors.

Gm Factors in Non-Human Primates

Eighteen different primate species have been typed for Gm factors present at the human γ(2b) and γ(2c) loci. Gm factors are absent in lower primates. The Gm factors, associated with γ(2C) molecules, namely, Gm(s), (c^5), (b^0) evolve first in the Cercopithecoidea species. Gm(z) occurs together with Gm(a) on human γ(2b) molecules, but in baboon sera Gm(z) occurs in the absence of Gm(a). The simultaneous occurrence of Gm(a) and (z) in the same sera is established in Hominoidea. Gm(b^3) is present only in gorillas, orangutans, and chimpanzees, while Gm(b4) and (c^3) was detected in chimpanzees. Polymorphism for the factors studied exists only in orangutans and chimpanzees. The data show a close correlation between taxonomic classification and the evolution of Gm factors.