Lymphocyte Fc receptors: the immunobiology and pathology of CD23.
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Biomedical subjects
Publications and source records attributed to M Hagen.
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The UL26 gene of herpes simplex virus type 1 (HSV-1) encodes a protease which is responsible for the C-terminal cleavage of the nucleocapsid-associated proteins, ICP35 c and d, to their posttranslationally modified counterparts, ICP35 e and f. To further characterize the HSV-1 protease, the UL26 gene product was expressed in Escherichia coli. The expressed protease underwent autoproteolytic processing at two independent sites. The first site is shared with ICP35 and results in removal of 25 amino acids from the C terminus of the protease. The second unique site gives rise to protein species consistent with deletion of a 28-kDa fragment at the N terminus. A mutant protease, which showed no activity in a mammalian cell cotransfection assay (F. Liu and B. Roizman, Proc. Natl. Acad. Sci. USA 89:2076-2080, 1992), failed to exhibit autoproteolytic processing at either site when expressed in bacteria. The inactive mutant was able to serve as a substrate in a trans assay in which the substrate and protease were coexpressed in bacteria. This experiment demonstrated that the unique N-terminal processing was mediated exclusively by the HSV-1 protease. ICP35 c,d also served as a substrate in this assay and was correctly processed by HSV-1 protease in E. coli. This trans-cleavage assay will aid in the characterization of HSV-1 protease and assist in investigation of the role of proteolytic processing in the virus.
We reported previously that CBA mice pretreated with dinitrophenyl-Bordetella pertussis (DNP-BP) conjugates exhibited sharply decreased anti-DNP IgE, and increased IgG2a antibodies following immunization with DNP-ovalbumin (DNP-OA) in alum. The objective of the present experiments was to determine whether the decrease in anti-DNP IgE was attributed to a regulatory effect exerted by IgG2a antibodies. Anti-DNP monoclonal antibodies (Mab) of the IgG1 or IgG2a isotype were passively transferred to mice, 24 h before a primary immunization with DNP-OA in alum. Anti-DNP IgE production was drastically suppressed in recipients of IgG1 but not of IgG2a Mab. Similar results were obtained when the Mab were endogenously produced by intraperitoneal implantation of anti-DNP-secreting hybridomas into (BALB/cxCBA)F1 (BCF1) mice. However, neither IgG1 nor IgG2a isotypes suppressed IgE antibody production if the hybridoma implantation took place 10 days after hapten priming. These results are, to our knowledge, the first to show a clear dissociation between the effect of either passively transferred or endogenously secreted IgG1 and IgG2a antibodies in their ability to inhibit a primary anti-hapten IgE antibody response.
The cycloburtane nucleoside analog (1R-1 alpha,2 beta,3 alpha)-9-[2,3-bis(hydroxymethyl)cyclobutyl]guanine [(R)-BHCG or SQ 34,514] was recently synthesized and shown to be the active enantiomer of (+/-)-BHCG (SQ 33,054), a potent inhibitor of several strains of herpesviruses [J. Med. Chem 34:1415-1421 (1991); Antiviral Res. 13:41-52 (1990)]. In plaque reduction assays, (R)-BHCG was about 1000 times more active than its S-enantiomer on herpes simplex virus type I (HSV-1) and over 200 times more active against a thymidine kinase-deficient mutant HSV-1 and human cytomegalovirus (HCMV). We now show that both (R)-BHCG and (S)-BHCG are efficiently phosphorylated to their mono-, di-, and triphosphates by HSV-1-infected cells, in a manner similar to that of acyclovir [Proc. Natl. Acad. Sci. USA 74:5716-5720 (1977)]. The uptake of both enantiomers was greatly increased upon infection; however, (S)-BHCG was taken up to about twice the extent of (R)-BHCG and accumulated primarily as the mono- and diphosphates. (R)-BHCG accumulated primarily as the triphosphate, and accumulation was linear with both time and added drug concentration. The triphosphate had an apparent half-life of about 10 hr. Metabolic studies using HCMV-infected cells showed only a small degree of phosphorylation of (R)-BHCG and none of (S)-BHCG. When cells were labeled with 25 microM (R)-BHCG, the amount of (R)-BHCG triphosphate formed was less than 0.5 pmol/10(6) cells. Interestingly, the ED50 value of (R)-BHCG is about 100-fold higher against HCMV than against HSV-1, and the relative levels of (R)-BHCG triphosphate formed in cells infected by the two viruses are roughly proportional to the antiviral activities.
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Immunization of mice with 2,4-dinitrophenyl-Bordetella pertussis (DNP-BP) failed to induce anti-DNP IgE responses. Administration of DNP-BP induced, however, the formation of anti-DNP IgE B memory cells, as demonstrated by adoptive transfer. Furthermore, mice pretreated with DNP-BP and primed with 2 micrograms DNP-ovalbumin (OA) in alum 2 weeks later produced high day-7 anti-DNP IgE levels. These subsided to near undetectable levels by day 12-14. The transient expression of serum IgE levels was accompanied by normal levels of anti-DNP IgG. The anti-OA response induced as a result of priming with DNP-OA in alum was not affected by pretreatment with DNP-BP. IgG subclass analysis revealed that mice pretreated with DNP-BP had elevated levels of IgG2a and reduced levels of IgG1 as compared to control (TNP-keyhole limpet hemocyanin-pretreated) mice. Treatment of mice with an anti-interferon-gamma monoclonal antibody, shortly after immunization with DNP-BP, not only reduced anti-DNP IgG2a levels, but prevented the sharp anti-DNP IgE decline that occurred after priming with DNP-OA in alum. These results suggest that DNP-BP-induced interferon-gamma production modulates Ig isotype expression in vivo in an anti-gen-specific manner.
This article describes a method of assigning a utility, or relative worth, to outcomes based on the mean interval to conception (MIC). In the formula MIC = 1/fC, the subscript C is the proportion of a given cohort of women who would conceive if given an infinitely long trial and fC is the fecundability or monthly probability of conception among this subgroup. MIC and MIO (interval of observation for those who do not conceive) are used as the utilities in decision analyses of fertility treatment. This method provides a semiquantitative estimate that reflects uncertainty of cure of infertility and variation in amount of time spent in the nonpregnant state after infertility treatment.
Metastatic lesions represent 1%-8% of all malignant tumours of the mouth and jaws, which are regarded as rare sites of metastases from different primary tumours. The vast majority of these lesions (90%) have been observed in the mandibula, and 5%-20% in the maxilla. Metastatic tumours in the oral soft tissue are very rare. The primary tumour that most commonly metastasizes to the mouth and jaws seems to be carcinoma of the lung, followed by breast cancer and renal cell carcinoma. The case of a 47-year-old woman with renal cell carcinoma and an intraoral soft tissue metastatic lesion is presented.
(R,S)-9-(3-hydroxy-2-phosphonomethoxypropyl)guanine [(R,S)-HPMPG] exhibits broad spectrum antiviral activity with an ED50 of less than 1 microM against herpes simplex virus (HSV) types 1 and 2, varicella zoster virus, human cytomegalovirus (HCMV) and vaccinia in plaque reduction assays. Wild type HSV-2 and its thymidine kinase deficient variant are equally sensitive to (R,S)-HPMPG. (R,S)-HPMPG is 100-fold more potent than acyclovir (ED50 = 0.45 microM vs. 44 microM, respectively) against HCMV in cell culture, and 10-fold more active than acyclovir in extending survival time in mice intraperitoneally infected with 70 LD50 HSV-1. However, (R,S)-HPMPG is toxic when administered repeatedly at 44 mg/kg/day in uninfected adult mice. The diphosphoryl derivative of HPMPG was enzymatically synthesized and is a competitive inhibitor of HSV-1 DNA polymerase relative to dGTP (K1 = 0.03 microM). HPMPG-PP is 70-fold less active at inhibiting HeLa DNA polymerase alpha than HSV-1 DNA polymerase. At concentrations between 0.3 and 1.5 microM (R,S)-HPMPG inhibited HSV-1 DNA replication greater than or equal to 50% in infected cells as measured by nucleic acid hybridization. Consistent with inhibition of viral DNA synthesis, 6 to 30 microM (R,S)-HPMPG reduces late viral polypeptide synthesis in HSV-1 infected cells. These data indicate that (R,S)-HPMPG is a thymidine kinase independent broad spectrum antiviral drug which is capable of inhibiting viral DNA polymerase.
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Adult lamprey were shown to produce antigen-specific antibody in response to weekly injections of human O-type erythrocytes ('O'-RBC) at both 17 degrees C and 9 degrees C. At the higher temperature, high titre antisera were produced earlier and at a faster rate than in animals kept at 9 degrees C. Lamprey kept at 9 degrees C, after a long lag period, eventually produced titres comparable to those obtained at 17 degrees C. Lamprey immunized and maintained at 9 degrees C were capable of producing high titres of antibody in response to second injection of antigen after the primary response titre had declined.
Histamine exerts its action in smooth muscle via in two types of receptors. In coronary arteries of pigs both types of receptors are also involved in responses to histamine. Histamine initiates by an interaction with H1-receptors a contraction and with H2-receptors a relaxation. The histamine-induced contraction is reduced by the competitively antagonistic action of mepyramine. Metiamide potentiates dose-dependently the histamine-caused contraction in the absence and presence of mepyramine. The proportion of H2-receptors in relation to H1-receptors is calculated.
Face, mouth and jaws represent seldom localisations of metastatic lesions. 5-20% of these lesions are reported with localisation in the maxilla, whereas 90% are found in the mandibula. Metastatic tumours in the oral soft tissue are very rare. The most common primary tumour seems to be the renal cell carcinoma. Only histological examination can give a differentiation against benign tumours. The diagnostic and therapeutic management of a 46 years old woman with a metastatic intraoral lesion of a renal cell carcinoma is presented.