Showing papers by "Kettering University published in 1983"

Central nervous system excitatory effects of meperidine in cancer patients

Abstract: The analgesic meperidine has been reported to produce signs of central nervous system excitation in human beings. To determine the relationship between signs and symptoms of central nervous system excitation and plasma levels of meperidine and normeperidine, we studied 67 patients receiving meperidine for the relief of postoperative or chronic pain. In 48 patients, excitatory effects ranging from mild nervousness to tremors, twitches, multifocal myoclonus, and seizures were directly correlated with accumulation of normeperidine in plasma. Evidence of compromised renal function occurred in only 14 of the 48 symptomatic patients, suggesting that renal dysfunction may contribute to but is not the sole factor in the accumulation of normeperidine or its relation to adverse neurological signs. In a second study we surveyed mood alterations in 47 patients receiving meperidine and 29 receiving other narcotic analgesics for postoperative pain. The repeated administration of meperidine was associated with adverse alterations in various elements of mood (e.g., apprehension, sadness, restlessness).

A rapid regulatory response governing nodulation in soybean.

Abstract: The number of nodules which develop on the primary root of soybean seedlings (Glycine max L. Merr) after inoculation with Rhizobium japonicum is substantially diminished in the region of the root developmentally 10 to 15 hours younger than the region maximally susceptible to nodulation at the time of inoculation. This rapid inhibition of nodulation has been investigated by inoculating soybean seedlings with rhizobia at two different times, 15 hours apart. Living R. japonicum cells, but not heterologous rhizobia or UV-killed cells of the homologous bacterium, were capable of eliciting the rapid inhibitory response. Nodulation responses to varying inoculum concentrations showed that bacterial dosages could be superoptimal, resulting in reduced nodulation and reduced inhibition of nodulation. When suspensions of R. japonicum were dripped uniformly onto the root surfaces, the degree of inhibition of nodulation in developmentally younger regions of the root was correlated with the number of nodules formed in the older and initially most susceptible region of the root. Nodulation in the developmentally younger region of the root, however, was affected very little if the first inoculum was restricted to contact with root cells in the region initially most susceptible to nodulation. The rapid regulatory response may be an important factor contributing to the clustering of nodules in the crown region of soybean roots in field-grown plants and the sparse nodulation commonly observed in younger regions of the root.

Combined Lipase Deficiency (cld): A Lethal Mutation on Chromosome 17 of the Mouse

Abstract: Two triglyceride lipases, lipoprotein lipase and hepatic triglyceride lipase, participate in the metabolism of plasma lipoproteins. A single recessive mutation, cld, on mouse chromosome 17 causes an apparent deficiency of both lipoprotein lipase and hepatic triglyceride lipase activities. Mice homozygous for this defect develop lethal hyperchylomicronemia within 2 days postpartum as a consequence of nursing. Plasma triglyceride values in affected mice often reach 20,000 milligrams per deciliter (100 times higher than that in normal littermates), and total lipase activity in plasma or tissues is 5 to 20 percent of that in controls.

Method for simple analysis of relative nucleic acid levels in multiple small samples by cytoplasmic dot hybridization

Abstract: ? 280 HRL/JEL Abstract A simple technique for the simultaneous measurement of relative levels of a specific mRNA in numberous small samples of biological specimens is described The technique involves denaturation of cytoplasmic preparations, followed by dotting of up to 96 samples onto a single sheet of nitrocellulose, hybridization with a 32P-labeled cDNA plasmid, autoradiography, and scanning By analyzing cytoplasmic preparations instead of purified RNA, manipulations of multiple samples prior to analysis are minimized Experiments with a clonal line of rat pituitary tumor (GH3) cells show that this technique can be employed to follow the induction by Ca2+ of prolactin mRNA sequences, employing cytoplasm prepared from as little as 25 x 104 cells The specificity of the technique for prolactin mRNA is shown by employing GC cells, a GH3 cell variant lacking detectable prolactin mRNA sequences Experiments with cultured rat hemipituitaries show that the prolactin mRNA present in cytoplasm corresponding to as little as 1/100 of a pituitary can be readily detected This technique is quite simple, can be quantified, and permits the ? 280 HRL/JEL simultaneous analysis of multiple samples while requiring very small amounts of material for analysis Hence, it should be quite useful for example for studies with various experimental systems of the regulation of specific mRNA levels

Reliability Analysis for Multistate Systems with Multistate Components

Abstract: An important problem in reliability theory is to determine the reliability of a complex system given the reliabilities of its components. In real life, the system and its components can be found in a range of states varying from perfect functioning through various levels of performance degradation to complete failure. This paper presents some models and their applications, in terms of reliability analyses, to situations where the system can have a whole range of states and all its components can also have a wide range of multiple states. Properties of the system structure function and computation and approximation of system state probabilities and system reliability measures are given.

Plasma levels and analgesia following deltoid and gluteal injections of methadone and morphine.

Abstract: The objective was to determine whether deltoid as compared to gluteal injection of morphine and methadone produce differential plasma levels and analgesic effects. Thirty-two postoperative cancer patients received deltoid and gluteal injections of morphine, 8 and 16 mg, within a double-blind, twin crossover design. Forty-four patients received deltoid or gluteal methadone, 10 mg. Deltoid morphine resulted in peak plasma levels 1.8 times (P less than 0.05) those observed following gluteal morphine. Deltoid methadone resulted in peak levels 2.5 times (P less than 0.005) those following gluteal injection. Deltoid morphine resulted in an area under the drug level-time (0 to 4 hours) curve 1.4 times (N.S.) the area observed following gluteal injection. Deltoid methadone resulted in an area under the drug level-time (0 to 4 hours) curve 2.2 times (P less 0.001) the area observed following gluteal injection. Deltoid methadone, but not morphine, provided greater (1.7-fold, P less than 0.05) pain relief than gluteal injection. If more rapid and enhanced analgesia is indicated, then the deltoid site may be preferable over the gluteal site for standard doses of methadone and other lipid soluble analgesics. In addition, the relative potency of compounds of widely differing lipid solubility may depend upon the site of intramuscular injection.

Increased sensitivity of lymphocytes from people over 65 to cell cycle arrest and chromosomal damage

Abstract: Flow cytometry revealed that, in the presence of tritiated thymidine, a greater percentage of phytohemagglutinin-stimulated lymphocytes from old human donors were arrested in the G2 or M phase than were cells from young donors. Furthermore, lymphocytes from old donors showed significantly more chromosomal damage than did lymphocytes from young donors. Lymphocyte cultures from old or young donors not exposed to tritiated thymidine had the same percentage of cycling lymphocytes in G2 or M, although the number of lymphocytes stimulated by phytohemagglutinin to enter the cell cycle was significantly lower in cultures from old donors. Thus, the impaired incorporation of tritiated thymidine by phytohemagglutinin-exposed lymphocytes from old humans reflects both an impaired proliferative response to phytohemagglutinin and an increased sensitivity to the radiobiological effects of tritiated thymidine.

Monoclonal antibodies to human gastrointestinal cancers and hybridoma method of production of the monoclonal antibodies

Abstract: A panel of monoclonal antibodies produced from human gastrointestinal tumors as immunogen is used to diagnose the presence of colon cancer. The antibody panel subsets the human gastrointestinal tract in its reactivity vis-a-vis esophagus, stomach, small intestine and colon. The panel is useful as a diagnostic probe for cancer.

Process for sex determination in man by use of monoclonal antibodies to the H-Y antigen

Abstract: Production of anti-H-Y hybridoma cell lines, and the use of the antibodies to determine the presence of H-Y antigen to indicate the sex of the proband inclusive of fetus, newborn and adult humans.

Clonal differences in response to T cell replacing factor (TRF) for IgM secretion and TRF receptors in a human B lymphoblast cell line

Abstract: A number of human B lymphoblast cell lines were tested to find a suitable model for induction of immunoglobulin-secreting cells (ISC) by T cell replacing factor (TRF). Partially purified TRF was size fractionated from the conditioned medium of irradiated (1000 rds) human spleen cells stimulated with pokeweed mitogen. IgM line SKW 6 showed high levels of TRF-stimulated immunoglobulin secretion and was chosen for cloning experiments. Clone 11 had a very low level of ISC with or without TRF (less than 0.1% ISC). Clone 4 had low background numbers of ISC (0.2%) and showed the highest degree of stimulation by TRF (to 6% IFC). High secreting clone 8-2 (6%) was not stimulated significantly by TRF. These clones had the same HLA-DR antigens, and their levels of ISC and sensitivity to TRF were relatively stable over three months of observation. The TRF preparation also had strong helper activity for normal peripheral blood B cell differentiation. TRF activity for both normal B cells and clone 4 cell line was absorbed by all 3 clones, but not by a pre-B line. This suggests that the effector molecules for normal B cell and cell line differentiation were the same. The three typical clones corresponding to nonresponding, responding, and high rate-secreting B cells provide basic models for analyzing B cell receptors for TRF and the biochemical effects of TRF during B cell differ entiation.

Physiology of Ex Planta Nitrogenase Activity in Rhizobium japonicum.

Abstract: Thirty-nine wild-type strains of Rhizobium japonicum have been studied for their ability to synthesize nitrogenase ex planta in defined liquid media under microaerobic conditions. Twenty-one produced more than trace amounts of acetylene reduction activity, but only a few of these yielded high activity. The oxygen response curves were similar for most of the nitrogenase-positive strains. The strains derepressible for activity had several phenotypic characteristics different from non-derepressible strains. These included slower growth and lower oxygen consumption under microaerobic conditions and lower extracellular polysaccharide production. Extracellular polysaccharide production during growth on gluconate in every nitrogenase-positive strain assayed was lower under both aerobic and microaerobic conditions than the non-derepressible strains. These phenotypic characteristics may be representative of a genotype of a subspecies of R. japonicum. These studies were done in part to enlarge the base number of strains available for studies on the physiology, biochemistry, and genetics of nitrogen fixation.

Complete nucleotide sequence of an immunoglobulin VH gene homologue from Caiman, a phylogenetically ancient reptile.

Abstract: Immunoglobulin variable (V) gene regions1–10 typify extensive multigenic families in terms of overall size, chromosomal arrangement and presence of large numbers of apparent pseudogenes. A unique mechanism of somatic reorganization involving recombination of VH, D and JH or VL and JL segments accompanies the differentiation of lymphoid cells5,6,11,12 and together with somatic mutation6,13,14 and other types of recombination15,16 accounts for V-region diversity. Although these processes have been well characterized in higher mammals, little is known concerning their origin and diversification during phylogenetic time. Previously, we described the blot-hybridization characteristics of murine VHIII probes with restriction enzyme-digested genomic DNA isolated from several phylogenetically critical species, including Caiman crocodylus, a modern representative of an ancient reptilian subclass17. Here we have used a murine probe, S107V, to select homologous clones from a library of Caiman genomic DNA constructed in a λ bacteriophage. The complete nucleotide sequence of a Caiman gene homologous to the murine VH gene and its adjacent 5′ and 3′ region is described. Comparison of the sequence with mammalian prototypes shows evidence of considerable organizational and structural homology extending outside the presumed VH-coding region and including elements believed to be involved in somatic recombination. Inferences about the evolution of this multigenic family can now be extended to the level of phylogenetic class.

Brief report: Linkage between G6PD and fragile‐X syndrome

Abstract: Eighteen Sardinian pedigrees segregating for the X-fragile site syndrome were studied with respect to the segregation of the fragile site (FS) at Xq28, mental retardation, and macro-orchidism. No exception was found in the association of this symptomatic triad (MOM-X) in 41 out of 42 patients examined. The exceptional individual had micro- rather than macro-orchidism and was found to have a 47, XXY sex chromosome complement. In six informative sibships, the MOM-X syndrome was found to segregate in close linkage association with G6PD-deficiency or protan colorblindness. The maximum likelihood estimate of recombination if 6% with 90% fiducial limits between 2.5 and 19.5% and an odds ratio in favor of measurable linkage of 428:1. However, no hint of measurable linkage was found in six pedigrees segregating for G6PD and the Renpenning syndrome or other unspecified types of X-linked mental retardation. These data give strong support to the generally held hypothesis that the FS at Zq28, characteristic of the MOM-X syndrome, is a direct expression of a genetic change in the same chromosomal region. They also clearly suggest that X-linked MR without FS may be the result of different allelic mutations at the same locus.

Activation of mammalian carcinogens to bacterial mutagens by microsomal enzymes from a pelecypod mollusk, Mercenaria mercenaria

Abstract: Several kinds of neoplastic diseases have been described in mollusks collected from the field. The etiology of these lesions is unknown; however, the involvement of chemical carcinogens has been suggested. Experimental models for chemically-induced neoplasia in bivalves have yet to be developed. We have obtained data which suggest that aromatic amines may be more appropriate candidates than polycyclic aromatic hydrocarbons for putative molluscan carcinogens. Digestive gland enzymes from a bivalve mollusk, Mercenaria mercenaria, were found to be able to convert aromatic amines to frameshift mutagens as detected by the Ames Salmonella tester strains. Extensive mutagenesis was obtained with 2-aminoanthracene, 2-aminofluorene, 2-acetylaminofluorene and 4-amino-trans-stilbene which are all mammalian procarcinogens. Mutagenic activation of benzo[a]pyrene and 3-methylcholanthrene was minimal. Low levels of aromatic amine-activating enzyme(s) were found in all tissues examined, but activity was greatest in the digestive gland. Enzymatic activity was heat-labile, NADPH-dependent, and apparently not inducible by polychlorinated biphenyls (Aroclor 1254).

Method for detecting the presence of GD3 ganglioside

Abstract: Mouse monoclonal antibody AbR 24 (Dippold et al., Proc. Natl. Acad. Sci. 77:6114-6118, 1980) has a high degree of specificity for human melanoma cells when tested on viable cultured cells using the PA-MHA serological assay. The antigen detected by this antibody has been isolated from melanoma cells and shown to be G D3 ganglioside by compositional and partial structural analysis and by comparison with authentic G D3 by thin layer chromatography (TLC). AbR 24 reacts with authentic G D3 , but not with any other ganglioside tested. Using TLC and reactivity with AbR 24 , a wide range of cells and tissues was examined for the presence of G D3 . A new serological assay, termed glycolipid-mediated immune adherence (GMIA), was devised for assaying the reactivity of AbR 24 with gangliosides. Melanomas (cultured cells or tumor tissue) were shown to have T D3 and G M3 as major gangliosides. Other cells and tissues examined also contained G D3 , but usually only in low amounts. Melanomas (and MOLT-4, a T-cell line) were characterized by a simplified ganglioside profile with G D3 and G M3 as major components. The apparent discrepancy between the ubiquitous presence of G D3 and the serological specificity of AbR 24 for melanoma cells can be explained in terms of localization and concentration of G D3 in different cells.