Showing papers by "Kettering University published in 1975"

Genetics of natural resistance to herpesvirus infections in mice.

Abstract: INHERITED resistance to virus infections has been demonstrated in several murine systems1–6. Susceptibility to mouse hepatitis virus3 and resistance to arbovirus7 infections in mice are dominant traits associated with the capacity of macrophages from the susceptible strains to replicate virus. Resistance to Friend leukaemia virus- and Gross leukaemia virus-induced leukaemogenesis is determined by at least two genes, one closely linked to the immune response genes of the mouse8. Conversely, susceptibility to lymphocytic choriomeningitis (LCM) virus infections in mice has been associated with a gene closely linked to the immune response genes9. The latter seems to be associated with the cell-mediated immune response to LCM which causes tissue damage and leads to death. Cell-mediated immunity seems to be important in resistance against herpes simplex virus (HSV) infections10–12. Analysis of the aspects of cell-mediated immunity which might be involved in resistance in man is complicated by the uncontrollable factors associated with activation of latent herpesvirus infections. I have developed a mouse model which has shown that at least three genes are responsible for resistance to HSV. Although preliminary evidence suggests that resistance is immunologically mediated, resistance genes do not seem to be closely linked to the histocompatibility region of the mouse.

Phagocytosis and cytolysis by a macrophage tumour and its cloned cell line.

Abstract: MACROPHAGES found in lymphoid and other tissues are defined by adherence, staining, morphology and rapid pinocytosis. Subtypes of macrophage-like cells have been distinguished on the basis of density and functional properties1–3. Immune macrophages4 and normal macrophages in the presence of specific antiserum5–8 will lyse relevant target cells, and can phagocytose cells by an independent mechanism9–12, but it has not been shown that the same cell type can carry out both functions.

Histocompatibility determinants in multiple sclerosis.

Abstract: It is the purpose of this review to present the accumulated data concerning the association between the major histocompatibility determinants and multiple sclerosis (MS). MS may be considered a model for investigating the association between a disease and the genetic factors of the major histocompatibility system (MHS), where the association with the ;;erologically defined (SD) HL-A antigens is only weak. This is of special interest because of observations in experimental animals, such as NZB mice with a lupus-like syndrome (Mellors et al. 1971), autoimmune murine thyroiditis (Rose et al. 1973), lymphocyte choriomeningitis (LCM) virus infection in the mouse (Oldstone et al. 1973) and murine leukemia (Lilly et al. 1964, Lilly 1972) which have been shown to be controlled by genetic factors within the HMS. The human counterparts, such as systemic lupus erythematosus, rheumatoid arthritis, Graves' disease, multiple sclerosis, Hodgkin's disease, lymphoma and leukemia, when studied with HL-A typing, have demonstrated only a weak association with the serologically defined determinants on the major histocompatibihty system.

The Azolla-Anabaena azollae relationship

Abstract: The heterocystous blue-green alga, Anabaena azollae, was isolated from the leaf cavities of the water fern, Azolla caroliniana, where it occurs as an endophyte. The isolated alga was capable of light dependent CO2 fixation and acetylene reduction. Aerobic dark acetylene reduction occurred and was dependent upon endogenous substrates. Vegetative cells of the alga reduced nitro-blue tetrazolium chloride (NBT) to blue formazan. Heterocysts did not. Heterocysts reduced triphenyl tetrazolium chloride (TTC) to red formazan faster than vegetative cells. Reduction of TTC by both heterocysts and vegetative cells was much more rapid than has been reported for free-living heterocystous blue-green algae. Both NBT and TTC inhibited acetylene reduction and CO2 fixation. The inhibition by TTC was more closely correlated to the time of exposure of the cells to the reagent and to the amount of deposition per cell than to the number of cells containing red formazan. No differential inhibition of acetylene reduction versus CO2 fixation was observed. Autoradiography showed that CO2 fixation occurred only in vegetative cells. Heterocysts caused a darkening of nuclear emulsions (chemography). This observation has been employed by others as an index of reducing activity in these cells. DCMU inhibited the acetylene reducing capacity of alga isolated from dark pretreated fronds more rapidly and to a greater extent than that in alga isolated from light pretreated fronds. Ammonia in excess of 5 mM was required before any inhibition of acetylene reduction was observed under either aerobic or anaerobic conditions in the light.

Polypeptide hormones of the thymus

Abstract: There are disclosed closely related new polypeptides isolated from bovine thymus, which are distinct polypeptides denoted as Thymin I and Thymin II or Thymopoietin I and Thymopoietin II, respectively. Thymin I may be characterized as having a relative mobility (Rf) on 7% polyacrylamide gel disc electrophoresis of 0.63 with respect to methyl green at a pH of 4.3, and having the following structural sequence: H 2 n--gly--gln--phe--leu--glu--asp--pro--ser--val--leu--thr--lys--glu--lys--leu--lys--ser--glu--leu--val--ala--asn--asn--val--thr--leu--pro--ala--gly--glu--gln--arg--lys--asp--val--tyr--val--gln--leu--tyr--leu--gln--his--leu--thr--ala--val--lys--arg--cooh Thymin II may be characterized as having a relative mobility (Rf) on 7% polyacrylamide gel disc electrophoresis of 0.57 with respect to methyl green at a pH of 4.3, and having the following structural sequence: H 2 n--ser--gln--phe--leu--glu--asp--pro--ser--val--leu--thr--lys--glu--lys--leu--lys--ser--glu--leu--val--ala--asn--asn--val--thr--leu--pro--ala--gly--glu--gln--arg--lys--asp--val--tyr--val--gln--leu--tyr--leu--gln--thr--leu--thr--ala--val--lys--arg--cooh Both polypeptides are highly purified and in powder form and are isolated from bovine thymus by multiple purification methods involving molecular sieving and chromatography. Both products cause delayed impairment of neuromuscular transmission in vivo and induce bone marrow cells to develop the characteristics of thymus-derived lymphocytes and thus are useful in therapeutic areas involving thymic or immunity deficiencies of imbalances, and neuromuscular hyperactivity.

Cell Proliferation in Epithelial and Lympho-hematopoietic Tissues of Cyclostomes

Abstract: The cyclostomes, hagfishes and lamprey, represent modern agnathans, the most primitive vertebrates. They are therefore of special interest from the phylogenetic view point with regard to proliferative activities of epithelial and of lympho-hematopoietic tissues. The animals, kept in aquaria at 15 C, were given 1.0 μCi of 3H-thymidine per gram of body weight intramuscularly, killed 2 hr later, different organs prepared for autoradiograms using the liquid emulsion technique, and the labeling indices determined. In peripheral blood, cell proliferation occurred mainly in the hemocytoblast group of cells in both species. Both lympho-hematopoietic cells and epithelial cells proliferated in the lamprey, although at a relatively low rate, perhaps attributable to senescence. In the hagfish, blood-forming and epithelial cells were rapidly proliferating, with the dramatic exception of intestinal epithelium, where the proliferative activity was extremely low. This Finding may well explain the documented high resistance of hagfishes to irradiation and alkylating agents, in contrast to the lamprey, which is approximately as sensitive to these agents as most advanced vertebrates.

Marrow Culture—a New Approach to Classification of Leukemias

Abstract: The agar culture technique has been used to study the proliferative characteristics of myeloid cells from patients with acute and chronic leukemia. A spectrum of qualitative abnormalities in proliferation and differentiation are characteristic of acute and chronic leukemias involving the myeloid series and are of value in classification of ‘unclassifiable’ leukemias. Correlations were observed between the initial growth pattern of leukemic cells and the subsequent remission rate. Reclassification of acute myeloid leukemia on the basis of growth pattern in vitro has allowed the detection of a substantial group of patients who are refractory to contemporary chemotherapy. Marrow culture and cell separation procedures applied to the acute leukemic termination of CML have revealed a subcategory of 17% of cases which did not display features of myeloid leukemia and the possibility that these represent early T-lymphocyte leukemias is discussed.

The relationship between the time of fractionated and single doses of radiation and hyperthermia on the sensitization of an in vivo mouse tumor.

Abstract: The present study was undertaken to explore the relationship of the time interval between application of heat and irradiation on enhanced tumor cell sensitivity. Using the Ridgway osteogenic sarcoma grown in AKD2F1/J mice, local tumor hyperthermia (42.5 +/- .5 degrees C for 15 minutes) was applied at various time intervals before or after single or fractionated doses of x irradiation. Enhancement of tumor cell sensitivity by combined treatment with radiation and heat, as measured by delay in tumor growth, cure rates, and mean survival times was inversely proportional to the time interval between application of both modalities. The interactions associated with this increased sensitivity appear to be transitory, diminishing with time between treatments. Possible mechanisms of action for thermal sensitization may involve the reduction of oxygen dependence as well as a reduced recovery capacity of tumor cells.

The thermochemical characterization of sodium dithionite, flavin mononucleotide, flavin-adenine dinucleotide and methyl and benzyl viologens as low-potential reductants for biological systems.

Abstract: The heat of reaction (deltaH) of Fe(CN)63-, Methyl Viologen, FMN and FAD with S2O42- in aqueous buffer solutions was measured calorimetrically. In addition deltaH values for reduction of Fe(CN)63-, FMN and FAD by reduced Methyl Viologen were determined. The resulting calorimetric data and corresponding E0 values were combined to yield thermodynamic data for these simple reducing agents in a form useful for applications to biological reactions. Thermodynamic data for the reduction of spinach ferredoxin are also presented.

Means for applying liquid to a relatively moving surface

Abstract: A dampening device supplying water or other ink repellent liquid to the printing plate of a lithographic offset rotary printing press, such device comprising a rotary cylinder, the wall of which comprises an inner coarse mesh element supporting an outer fine mesh element that picks up water from a trough into which it dips and from which the water is projected as a spray by means of air impinging on the interior surface of the cylinder at a delivery station from a series of nozzles or a tube having an axial slot, the fine mesh element having a mesh size that will ensure that each aperture is spanned by the liquid, and the coarse mesh element having apertures of a size such that they are not so spanned, and the space between the cylinder and the printing plate or transfer cylinder of the printing press being unobstructed in the circumferential direction.

Peak discrimination as a method for quantitative evaluation of neural activity by computer.

Abstract: A computer method (PDP-12) for the quantification of neural activity in single- as well as few-fibre preparations of nerves was devised and tested on function-generator signals and on neurograms from baro- and chemoreceptor fibres of the carotid sinus nerve of rabbits. The principle of the program was to search continuously for maxima and minima of the electrogram regardless of the absolute voltage range in which they occurred. Action potentials were then distinguished from noise by comparing these maxima with amplitude discriminators. The latter were derived from the previous analysis of noise in selected neurograms and in recordings during activity-free intervals of the normal electrogram or temporary cold block of the preparation. From peaks accepted as action potentials the program computed total mean frequency, amplitude histogram and interval histogram as standard outputs. The method permitted one to determine in few-fibre preparations not only total activity but also response characteristics of different fibre components. However, owing to principal limitations shown to be inherent in such techniques, the exact quantification of neurograms from several fibres became impossible if the mean frequency—depending on the type of activity—exceeded several hundred to about 1000 impulses/s. By systematic variation of program parameters and type and rate of neural activity, the performance characteristics of the program as well as certain general properties of single-, few- and multi-fibre neurograms were evaluated.

The detection of aberrant DNA synthesis in a member of a high-risk cancer family.

Abstract: Relatives of patients with multiple polyposis are among those at high risk for development of neoplasms in the colon. Examination of 4 siblings, 3 men and 1 woman, of a patient with multiple polyposis was conducted for the possible presence of colonic polyps. All patients were over 40 years of age and received barium enemas for the radiological detection of excrescences. Proctoscopic examinations were also carried out during which time a biopsy and colonic wash were obtained. Polyps were absent on films as well as on endoscopy, and colonic cytologies of all 4 subjects were within normal limits. However, isotopic incorporation studies revealed the presence of an abnormal labeling pattern in some crypts of the biopsy incubated with TdR-3H of 1 family member. Along with normal crypts with label in the lower two-thirds of the colonic crypts, some were seen to have cells labeled at the surface, a proliferative lesion thought to precede the apperarance of a polyp. Among the surface cells removed by the colonic wash, some were found to be isotopically labeled, that is, engaged in DNA synthesis. Thus, a defect in the regulation of colonic epithelial cell replication was found, suggesting the need for close surveillance in the interest of early colon cancer detection.

Method of and machinery for producing bookblocks

Abstract: A method and apparatus for assembling a block for a book or book section in a 2-up coming and going method of bookmaking by providing a stream of groups of book elements, each group containing all the primary pages of the book or book section. The groups of the stream are divided into first and second series and the groups of the first series are conveyed to a combining station around a turn-over member rotating about a horizontal axis so that each group of the first series is turned through 180°. The groups of the second series are separately conveyed to the combining station and each group is arranged to be in half-block form before it reaches the combining station. At the combining station, the half-blocks of the series and the half-blocks of the second series are brought together in pairs by bringing each half-block of one series under a half-block of the other series to form blocks each comprising a half-block of the first series and a half-block of the second series. The passage around the rotary member causes each half-block of the first series to arrive at the combining station in an orientation in which it has been turned through 180° about an axis parallel to the junction between the two pages of each leaf of the half-block relative to the orientation of each half-block of the second series arriving at the combining station.

Relationship between structure and function of lower vertebrate immunoglobulins.

Abstract: In order to elucidate both macromolecular and genetic bases for the functional diversity expressed by immunoglobulins, extensive studies of their primary, secondary, tertiary and quaternary structure have been undertaken (1–3). Early in the course of these investigations, it became apparent that antibody function was associated with a heterogeneous group of multimeric glycoproteins and that more than one gene controlled the synthesis of individual immunoglobulin subunits. The mechanism whereby the separate gene products are generated (somatic mutation or germ line accumulation) and ultimately integrated are not fully understood (4, 5). As biologic processes such as antibody formation may have become more complex during the passage of evolutionary time, one major direction in the investigation of adaptive humoral immunity has been to evaluate the immune response and antibody structure in phylogenetic perspective. Although the characterization of lower vertebrate immunoglobulins is not as complete as that of the mammalian counterparts, sufficient detail of their structure is known to permit meaningful phylogenetic comparisons. This presentation will first outline the central structural features of mammalian IgM and IgG, compare the structures of lower and higher vertebrate forms of immunoglobulins, relate immunoglobulin structure to active site formation and expression and discuss the origins of non-immunoglobulin mediated “immune-like” recognition in invertebrate and vertebrate species.

Goods container for transport purposes

Abstract: For facilitating the picking up and setting down of a container in a containerised goods transport system, there is provided at each corner of the container a lifting arrangement comprising a retractable leg housed with an operating ram in a post which is mounted by hinges on a corner frame member to swing about a vertical axis between a position laterally outboard of the container to allow the leg to be extended, and a stowed position in which the post with leg retracted is housed in a recess in a corner frame member so occupying otherwise non-used space

A study of complement components C3, C5, C6, C7, C8 and C9 in chronic membranoproliferative glomerulonephritis, systemic lupus erythematosus, poststreptococcal nephritis, idiopathic nephrotic syndrome and anaphylactoid purpura.

Abstract: In a comparative study the hemolytic activity of C3, C5, C6, C7, C8, C9 and the C3 proactivator (C3PA) were measured in sera of 22 patients with chronic membrano-proliferative glomerulonephritis (CMPGN), 15 patients with idiopathic nephrotic syndrome, 10 patients with systemic lupus erythematosus, 7 patients with anaphylactoid purpura and 10 patients with acute poststreptococcal nephritis. In CMPGN, C3, C5, C6, C7 and C8 were low in the majority of the patients, whereas C9 and C3PA were depressed only in 21% and 11% of the patients, respectively. By contrast, C3PA and C8 showed striking depressions in idiopathic nephrotic syndrome. In lupus erythematosus, all the C factors, including C3PA were found to be low with the exception of C9, which was normal in 80% of the patients studied. C3, C5, C6 and C7 were found to be depressed in acute glomerulonephritis; C8 and C9 titers were normal. In all patients studied with anaphylactoid purpura, CH50 and C3 titers were elevated markedly.