Participation of the chemotactic system in regulating cell division in Escherichia coli

The possible role of the chemotaxis system in regulating cell division of Escherichia coli was studied. Attractants increased the rate of division whereas repellents reduced it. Non-metabolisable attractants analogues were also effective in stimulating cell division. Fucose, a non-metabolisable analogue of galactose, increased the rate of division by 20-25%. Co2+ at concentrations which had no effect on the tar-mutant division suppressed the division of the wild type. Likewise, indole at concentrations which did not influence the division of the tsr-mutant, suppressed the division of the wild type.     

Genetic regulation of the antibody response to H-2Db alloantigens in mice

The cytotoxic antibody response to the H-2D^b alloantigen has been investigated in ten strains of the C57BL/10 background. Three types of responses could be distinguished: no detectable response, an IgM response, and an IgG response. The IgG response is influenced by the D and probably the I-A region of the H-2 complex, whereas the IgM response is dependent on the allele for the E chain. The hypothesis is proposed that regulatory T cells, which recognize the antigen in context of self MHC molecules, determine the outcome of an anti-H-2D^b immunization in which the I-E molecule restricts the IgM response and the I-A molecule restricts the IgG response; the D molecule is probably responsible for activation of suppressor T cells which suppress only the IgG response.     

Influence of clonidine on the acute tolerance pattern to morphine induced analgesia and sensitivity changes in mice

Pretreatment with clonidine inhibited the acute tolerance development to morphine-induced analgesia and sensitivity changes of the smooth muscles to exogenous acetylcholine and norepinephrine in mice. Clonidine per se enhanced the responsiveness of mouse ileum and vas deference to the above agonists and no signs of tolerance was evident for this effect and to its analgesic activity.     

H-2 polymorphisms in outbred strains of mice

We studied H-2 polymorphisms of five outbred strains, CF1, ddY, ddN, ICR and KUNM, using 15 alloantisera to H-2 class I private antigens. All individuals had at least one private antigen at H-2K and/or H-2D. The number of H-2 class I private antigens in each strain were three in ddY, four in ICR, five in CF1, and seven in ddN and KUNM. The number of H-2 phenotypes were five in ddY, six in CF1 and ICR, twelve in ddN and seventeen in KUNM. Each strain had strain specific antigen(s) which discriminated each strain from the other strains. The CF1 strain had the H-2.23 and H-2.32 antigens controlled by the H-2k haplotype at a frequency of about 70%. The ddN strain had H-2.4 (H-2Dd) at a frequency of 37.8%. The H-2.9 antigen (57%) governed by H-2Df was distributed only in the KUNM strain. Both the ddY and ICR strains possessed H-2.17 and H-2.30 antigens (85-97%) which were controlled by the H-2q haplotype. The H-2 locus will be useful to characterize each strain and distinguish between strains, and for monitoring of outbred strains by H-2 gene frequency.     

Inability of mice to generate cytotoxic T lymphocytes to vesicular stomatitis virus restricted to H-2Kk or H-2Dk

H-2k mice are unable to generate cytotoxic T lymphocytes (CTL) to vesicular stomatitis virus (VSV). This apparent unresponsiveness is found for both major serotypes of VSV, VSV-Indiana and VSV-New Jersey. CTL unresponsiveness occurs despite the ability of H-2k mice to generate a humoral immune response against VSV that is comparable to that found in responder (H-2b and H-2a) strains. All H-2k mice regardless of background genes, including various Ig allotypes, were found to be nonresponders. H-2k-linked unresponsiveness mapped to both H-2Kk and H-2Dk and occurred despite the presence of responder alleles in (responder x nonresponder)F1 mice. The unresponsiveness cannot be attributed to an inability of VSV-infected H-2k target cells to express viral surface antigens of H-2 molecules. Further, unresponsiveness cannot be overcome by using secondary stimulation in vivo or in vitro. H-2k-linked unresponsiveness does not appear to be due to suppression, and no complementation has been found in various (nonresponder x nonresponder)F1 mice. Thus unresponsiveness to VSV in association with H-2Kk or H-2Dk appears to represent an extensive defect of immune responsiveness that probably occurs because VSV is not a natural mouse pathogen.     

H-2 class I loci determine sensitivity to MCMV in macrophages and fibroblasts

Peritoneal (PM) and bone marrow-derived (BMM) macrophages and lung fibroblasts (LF) from inbred, intra-H-2 recombinant, H-2 mutant, and hybrid mice were infected with murine cytomegalovirus (MCMV) under centrifugal enhancement. At the concentration of virus employed, peritoneal macrophages from strains carrying Kd, Kb, D^d, KS and/or D^s, K4 and/or D4 alleles could be infected to a level of 80%–100%, as assessed by viral antigen expression or loss of Fc receptors. Cells lacking these haplotypes and carrying K^k, K^f, D^k, Df, or Db were resistant, yielding levels of infection below 20% . The background (non-H-2) and class II genotype and the S allele did not influence the proportions of cells infected. Furthermore, sensitivity was dominant in the F, progeny of H-2 b x H-2 k and H-2d x H-2 k crosses, and was not compromised by thebm1, bm3, bm10, or bm14 mutations in the al or2 regions of Kb orD ^b. The proportions of cells able to release infectious virus were low, but paralleled the frequencies of viral antigen expression. The class I genotype also determined susceptibility to MCMV infection in BMM and LF, although up to 35% of H-2 k BMM and 46% of H-2 k LF could be infected. The findings are consistent with an association between K and D antigens and a cellular receptor for MCMV on all three cell types.     

Genetic control of sensitivity to Moloney leukemia virus in mice. II. Mapping of three resistant genes within the H-2 complex.

The level of viremia and the appearance of leukemias were studied after inoculation wtih Moloney leukemia virus (M-MuLV) in different H-2 congenic strains of mice. The viremia was regularly measured on individual mice with a radioimmunoassay of the major internal virion component p30. Three genes within the major histocompatibility complex controlled the level of circulating virus. Two of them, called Rmv.1 and Rmv.2, appear to be located in the I region, respectively, in the IA, and the IC-S or G regions. The third gene, Rmv.3, was mapped to the D end of the complex in the D or T region. Crosses between resistant and sensitive strans demonstrated that the H-2 associated resistance was inherited as a dominant or semi-dominant Mendelian trait. Rmv.1, Rmv.2, and Rmv.3 were shown to complement for resistance in trans when the hybrids between sensitive strains were examined. A good correlation was found between viremia and the appearance of leukemias, the most viremic strains being also the most leukemic. Nevertheless, additional non-H-2 genes must control viremia and/or the appearance of leukemia since, despite high levels of viremia, some sensitive strains do not become leukemic.     

Participation of leu-enkephalin in regulating carbohydrate metabolism

The experiments have been performed on 166 white male rats with a mass of 180-220 g. It has been revealed that leucine-enkephalin and its synthetic analogs prevent an increase in glucose blood levels and a decrease in glycogen liver levels caused by adrenaline and parathyroid hormone. At the same time the enkephalins inhibit the secretory activity of pancreatic beta-cells. The mechanisms of opioid peptide effect on carbohydrate metabolism are discussed.     

Individual differences in the levels of pain sensitivity and analgesic effect of morphine in noninbred mice

The initial threshold of pain sensitivity and the degree of morphine analgesia (12, 12, 70 mg/kg, i. p.) were assessed during mechanical, thermal and electrical stimulation, respectively, in noninbred white male mice. Two tests were performed, the second a week after the first one. A slight positive correlation (r = +0.39) between the initial threshold of pain reaction and the analgetic effect of morphine was found only during electrical stimulation in the first test, and positive correlation between the first and the second test during electrical and mechanical stimulation (0.34 and 0.27, respectively) was determined. The degree of morphine analgesia in different animals during second testing could either increase or decrease. It is suggested that previous testing of morphine analgetic effect cannot predict the efficacy of analgesia during the second testing and that the initial threshold of pain sensitivity cannot serve as a reliable predictor of morphine analgesia level.     

Proximity of the Mep-1 Gene to H-2D on chromosome 17 in mice

The Mep-1 gene on chromosome 17 in mice controls the activity of meprin, a kidney brush border metalloendopeptidase. Most inbred mouse strains of the k haplotype (e.g., CBA, C3H, AKR) are markedly deficient in meprin activity; these mice carry the Mep-1^ballele. Mouse strains in which meprin activity levels are normal are designated Mep-1^a Studies using congenic and recombinant strains mapped the Mep-1 gene telomeric to H-2D near the Tla gene. To further study the relationship between the major histocompatibility complex and Mep-1, a linkage study was conducted. Mep-1^a F₁ hybrids [C3H.A (K^kD^d) × C3H.OH (K^dD^k)] were backcrossed with Mep-1^b C3H.OH (K^dD^k) parents. The progeny were assayed for H-2D markers, Pgk-2 isozymes, and meprin activity. Recombination between H-2D and Mep-1 occurred in 6 out of 284 mice, a crossover frequency of 2.1%. Mep-1 is therefore 2.1 crossover units telomeric to H-2D and approximately 0.6 crossover units from Tla. The Mep-1 locus provides a new genetic marker for the future mapping of this important area of the mouse genome.     

Genetic control of sensitivity to Moloney leukemia virus in mice V. Role of H-2-linked genes in the control of anti-FMR cytolytic T lymphocytes

Three H-2-linked genes, Rmv1, Rmv2, and Rmv3 control the resistance of mice against Moloney virus (MLV)-induced leukemias. It has been shown previously that they function as immune response (Ir) genes regulating the level of antivirus antibodies. In the present experiments, the cell-mediated anti-tumor response has been studied in a series of inbred strains selected for their resistance or sensitivity to the MLV-induced disease. We failed to detect any relationship between resistance and sensitivity and the ability to produce cytolytic T lymphocytes (CTL) directed against the virus-induced FMR cell surface antigen. Furthermore, the role of each Rmv gene has been studied separately using congenic pairs of mice differing at only one of these loci: we failed to evidence any influence of these genes in the cell-mediated antitumor reactions as measured by the ability to lyse syngeneic FMR(+) target cells. Nevertheless a gene mapping in the D region of the MHC but probably different from Rmv3 controls the response of a subset of anti-FMR CTL restricted by the H-2K^k antigens, with higher response in H-2D^d than in H-2D^b animals. This observation confirms the existence of H-2D region associated Ir genes regulating the CTL-mediated antitumor immune responses by choosing the subset of responder CTL, and suggests that a fourth H-2-linked gene plays some role in the genetic control of the anti-FMR immune response.     

Functional changes in murine macrophages infected with cytomegalovirus relate to H-2-determined sensitivity to infection

Peritoneal macrophages were infected with murine cytomegalovirus in vitro, and indices of infection and macrophage function were monitored over 4 days. When the cells were assessed for the expression of viral antigen or for cytopathic effects, infection was found to be solely determined by the H-2 phenotype. Less than 10% of the macrophages from resistant H-2k strains were affected, whereas 90% of H-2d cells and approximately 80% of H-2b and H-2a cells became infected. Similar trends were demonstrable by the measurement of viral DNA. In H-2a cells (B10.A), Dd conferred sensitivity despite the resistant K and class II phenotype. The findings suggest a critical association between the class I antigens and an early stage in the infectious process. Indices of infection were paralleled by a loss of Fc receptor expression and optimal colloidal gold uptake, whereas most cells remained trypan blue negative, retained dehydrogenase and acid phosphatase activities, and did not release infectious virus during the period of study. This is consistent with a role for macrophages in the persistence of cytomegalovirus in the host.