Showing papers by "Tufts University published in 1985"

Regulation of bone mass by mechanical strain magnitude

Abstract: The in vivo remodeling behavior within a bone protected from natural loading was modified over an 8-week period by daily application of 100 consecutive 1 Hz load cycles engendering strains within the bone tissue of physiological rate and magnitude. This load regime resulted in a graded dose:response relationship between the peak strain magnitude and change in the mass of bone tissue present. Peak longitudinal strains below 0.001 were associated with bone loss which was achieved by increased remodeling activity, endosteal resorption, and increased intra-cortical porosis. Peak strains above 0.001 were associated with little change in intra-cortical remodeling activity but substantial periosteal and endosteal new bone formation.

Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation.

Abstract: Polyoma middle-T antigen is required for viral transformation of cultured cells and for tumorigenesis in animals. Like many other transforming gene products, middle-T is bound to the membrane and has an associated tyrosine kinase activity in vitro1,2. This activity seems to result from the interaction of middle-T with pp60c-src, the cellular homologue of the transforming gene product of the Rous sarcoma virus, pp60v-src (refs 3–5). Both pp60v-src (ref. 6) and another retrovirus transforming gene product, pp68v-ros (ref. 7) were shown recently to have an associated phosphatidylinositol (PI) kinase activity in vitro and to increase PI turnover in vivo. These results suggest that viral transformation may be directly connected to a complex network of second messengers generated from PI turnover8–18. Here, we assayed for PI kinase activity in immunoprecipitates made with middle-T- or pp60c-src-specific antisera of cells infected with polyoma virus. A PI kinase activity was detected in those immunoprecipitates which contained middle-T. Studies of mutants of middle-T defective in transformation indicate a close correlation between PI kinase activity and transformation.

Gravitational radiation from cosmic strings

Abstract: Gravitational radiation from oscillating loops of string is studied both analytically and numerically. The total radiated power is found to be P=\ensuremath{\gamma}G${\ensuremath{\mu}}^{2}$, where \ensuremath{\mu} is the mass density of the string and \ensuremath{\gamma} is a numerical coefficient \ensuremath{\sim}100. The intensity and the spectrum of the stochastic gravitational-wave background produced by the loops are calculated. Gravitational radiation from asymmetric loops carries not only energy, but also momentum; the loop recoils and accelerates like a rocket. The momentum radiation rate from loops is calculated and it is shown that cosmological loops formed with sufficiently small initial velocities are slowed down by dynamical friction and do not rocket away.

An update on human interleukin-1: from molecular biology to clinical relevance

Abstract: Interleukin-1 (IL-1) represents a family of polypeptides with a wide range of biological activities. At least two dissimilar gene products have been cloned; there are probably more. The human IL-1 family plays an important role in the pathogenesis of many diseases and functions as a key mediator of the host response to various infectious, inflammatory, and immunologic challenges. Recombinant mouse (pI 5) and recombinant human (pI 7) IL-1's are being used to confirm the multiple biological properties of IL-1's but considerable investigation is required before the specific activities (biological units per milligram of protein) are established for each human IL-1 form. Some IL-1 biological activities such as the induction of hepatic acute-phase protein synthesis have been demonstrated in invertebrates predating the evolution of lymphocytes. IL-1 is highly inflammatory and increases the concentration of metabolites of arachidonic acid, most notably prostaglandin E2, in brain, muscle, chondrocytes, and synovial fibroblasts. The synthesis of leukotrienes also is involved in the mechanism of its action on certain tissues. The cloning and expression of human IL-1 genes will expand our understanding of IL-1 in various diseases through improved detection systems and the use of cDNA probes; the development of IL-1 antagonists, as well as the use of IL-1 as an immunomodulator, is presently being considered.

Increased plasma interleukin-1 activity in women after ovulation

Abstract: The polypeptide interleukin-1 mediates many host responses to infection and inflammation. A method was developed for studying interleukin-1 levels in human plasma from febrile patients. Interleukin-1 activity was also consistently found in plasma samples from women in the luteal phase of their menstrual cycle. This activity was neutralized by a specific antiserum to human interleukin-1 and was low in plasma from healthy men and preovulatory women. Thus interleukin-1 appears to have a role in normal physiological conditions as well as in disease states.

Regional Mitochondrial Respiratory Activity in Huntington's Disease Brain

Abstract: : This study investigated mitochondrial respiratory activity in Huntington's disease (HD) brain. Mitochondrial membranes from caudate and cortex of HD and non-HD autopsied brains were assayed for succinate oxidation, cytochrome oxidase activity, and cytochromes b, cc1, and aa3. There was a significant decrease in HD caudate mitochondrial respiration, cytochrome oxidase activity, and cytochrome aa3, whereas cytochromes b and cc1 were normal. These findings are consistent with the hypothesis that mitochondrial dysfunction may contribute to the localized hypometabolism and progressive atrophy of the HD caudate.

Unique allelic restriction fragments of the human Ha-ras locus in leukocyte and tumour DNAs of cancer patients

Abstract: White blood cell DNA from cancer patients and DNA from tumours and tumour-derived cell lines frequently demonstrated allelic restriction fragments of the Harvey ras oncogene locus not found in the unaffected population. The presence of such unusual alleles may be linked to susceptibility to cancer.

Vasoactive intestinal peptide is a physiological mediator of prolactin release in the rat.

Abstract: To determine whether VIP functions as a physiological PRL-releasing factor, the effects of immunoneutralization of endogenous vasoactive intestinal peptide (VIP) on the PRL secretory response to suckling and ether stress were assessed. Using a porcine VIP-thyroglobulin conjugate as antigen, a peptide-specific antiserum was generated in a rabbit which bound porcine VIP with a Kd of 5.1 X 10(-11) M and a maximum binding capacity of 1830 ng/ml. In a RIA, this antiserum demonstrated immunoreactive VIP in tissue extracts of various regions of the brain and gastrointestinal tract. IR VIP in extracts of cerebral cortex and hypothalamus coeluted with synthetic porcine VIP on Bio-Gel P-30 column chromatography. Using chronically implanted right atrial catheters for blood sampling to avoid effects of stress and anesthesia, PRL blood levels in normal controls began to rise almost immediately after initiation of suckling from basal values of 3.0 +/- 0.9 ng/ml to reach a plateau of 158.1 +/- 33.5 ng/ml after 40 min. When the VIP antiserum was administered immediately before initiation of suckling, the onset of the PRL response was delayed by 40 min, but PRL levels then rose at a slower rate to reach the plateau level of normal animals approximately 80 min later. When VIP antiserum was administered to rats who had been suckling for at least 1 h, PRL levels fell from a mean basal elevated level of 152.7 +/- 16.0 ng/ml to a nadir of 50.4 +/- 9.1 ng/ml 80 min after injection and then gradually returned to basal levels. The effect of VIP antiserum was studied in rats in whom PRL secretion was increased by exposure to ether, a stimulus that acts on the release phase of PRL secretion. In rats in whom the depletion-transformation of PRL was induced by a prior brief period of suckling, subsequent exposure to ether caused a rise in serum PRL levels. The response was completely blocked in rats given VIP antiserum, whereas animals given nonimmune serum showed a significant increase in serum PRL to 38.6 +/- 17.3 ng/ml. We conclude from these studies that VIP mediates the acute PRL response to suckling and is required for maintenance of PRL levels in continuously suckling animals but is not the only factor causing PRL elevation. Complete abolition by the VIP antiserum of the PRL response to ether indicates that the effect of the anesthetic is mediated entirely by the release of VIP. These findings are consistent with the view that VIP is a physiological PRL-releasing factor in the rat.

Isolation of T-Lymphotropic Retrovirus Related to HTLV-III/LAV from Wild-Caught African Green Monkeys

Abstract: Present evidence suggests that the acquired immune deficiency syndrome (AIDS) emerged in Central Africa as a new disease in recent decades. This disease has recently approached epidemic proportions in many parts of the world. The etiologic agent of AIDS is believed to be the virus HTLV-III/LAV, which has been proposed as having originated from a recent simian-human transmission in Africa. This report describes the isolation of a designated STLV-IIIAGM retrovirus closely related to HTLV-III/LAV from seven healthy wild-caught African Green monkeys (Cercopithecus aethiops) that showed the presence of antibodies designated STLV-IIIAGM. In vitro growth characteristics, ultrastructural morphology, and major proteins of 160,000 kilodaltons (kD), 120 kD, 55 kD, and 24 kD are similar to and cross-reactive with the analogous antigens of HTLV-III/LAV. The use of these serologic markers in the detection of STLV-IIIAGM-infected monkeys may be important in assuring the continued safety of a variety of biologic reagents that are derived from these primate species. The existence of a retrovirus closely related to HTLV-III/LAV that naturally infects an African nonhuman primate in the apparent absence of disease may provide a unique model for the study of human AIDS and the development of an effective vaccine.

BLAST-2 [EBVCS], an early cell surface marker of human B cell activation, is superinduced by Epstein Barr virus.

Abstract: Activation of human B cells by pokeweed mitogen (PWM), protein A, anti-IgM, or EBV infection results in the expression of a new surface antigen, termed BLAST-2 [EBVCS]. This marker appears before the cells undergo blast transformation as assessed by the initiation of DNA synthesis and expression of the BLAST-1 antigen. Thus, the BLAST-2 [EBVCS] antigen is expressed on both activated and lymphoblastoid cells. The antigen is, in addition, restricted to B cells, as it is not found on cells of T or myeloid lineage derived from peripheral blood, cell lines, or neoplastic cells. However, it is readily detected on chronic lymphocytic leukemia cells of B cell origin and in the germinal centers of tonsils and lymph nodes. Like the BLAST-1 antigen, BLAST-2 [EBVCS] is expressed at a high level only on EBV-transformed B lymphoblasts and has a m.w. close to 45,000. Immunoprecipitation experiments show, however, that the two antigens are expressed on distinct populations of molecules.

Primal and Dual Capacity Utilization: An Application to Productivity Measurement in the U.S. Automobile Industry

Abstract: Capacity utilization measures have traditionally been constructed as indexes of actual, as compared to “potential,” output. This potential or capacity output (Y*) can be represented within an economic model of the firm as the tangency between the short- and long-run average cost curves. Economic theoretical measures of capacity utilization (CU) can then be characterized as Y/Y* where Y is the realized level of output. These quantity or primal CU measures allow for economic interpretation; they provide explicit inference as to how changes in exogenous variables affect CU. Additional information for analyzing deviations from capacity production can be obtained by assessing the “dual” cost of the gap. In this article the definitions and representations of primal-output and dual-cost CU measures are formalized within a dynamic model of a monopolistic firm. As an illustration of this approach to characterizing CU measures, a model is estimated for the U.S. automobile industry, 1959–1980, and primal and dual CU...

The effect of an academic examination on salivary norepinephrine and immunoglobulin levels.

Abstract: Forty-six college students provided saliva samples just after taking an examination, one hour and 45 minutes later, and several days later, at a period of rest. As compared with baseline levels, the power stress of an examination was associated with an increase in salivary immunoglobulin A (S-IgA), a measure of B-cell immune function, and with an increase in norepinephrine (NE) concentrations in the saliva. The increase in NE was greater for those for whom n power was greater than n affiliation rather than for those for whom the reverse was true. Greater increases in, and levels of, NE at the examination and after were associated with greater subsequent drops in S-IgA, which reached below baseline levels for those for whom n power was stronger. The examination stimulated adrenergic activity, which in the long run depressed immune function for those with a strong power motive who had been most aroused adrenergically by the examination.

Characterization of human bone cells in culture.

Abstract: Cultures of human bone cells were established, maintained, and characterized with respect to several metabolic parameters. These studies were undertaken with a view to using the bone culture system as a means of studying mechanisms of bone metabolism. The donor patients' ages ranged from 1 to 90 years and their disease states included congenital limb anomalies, exostosis, and osteo- and rheumatoid arthritis. Cultures were maintained up to 5 months. The osteoblast-like character of these cells was confirmed with the use of measurements applied to bone cells from other systems. Analyses showed that (a) the cells' appearance resembled that of cultured osteoblasts from other animal sources, b) intracellular cAMP was stimulated by human parathyroid hormone, c) osteocalcin was detected in the medium of all tested bone cell cultures and its production was found to be stimulated by 1,25-dihydroxycholecalciferol, and d) newly synthesized collagen was almost exclusively type I.

Imipramine and desipramine disposition in the elderly.

Abstract: Forty-six healthy male and female volunteers aged 21 to 88 received single 12.5-mg i.v. doses of imipramine, and 35 of these people received single 50-mg p.o. imipramine doses on a different occasion. Thirty-five similar volunteers received single 50-mg p.o. desipramine doses. Among these subjects 25 participated in studies of both imipramine and desipramine. Kinetic variables for the respective drugs were determined from multiple plasma drug concentrations from samples obtained during 96 hr after the dosage. Imipramine half-life was markedly prolonged in elderly vs. young males (28.6 vs. 16.5 hr; P less than .001) and females (30.2 vs. 17.8 hr; P less than .01) due to decreased clearance (males: 567 vs. 945 ml/min, P less than .01; females: 599 vs. 975 ml/min, P less than .005) with no change in volume of distribution. After p.o. imipramine doses time to peak imipramine concentration was shorter in elderly females (2.1 vs. 4.8 hr; P less than .005) but no different in males. Peak concentration achieved was greater in the elderly of both sexes (males: 40.2 vs. 19.5 ng/ml, P less than .005; females: 44.7 vs. 10.4 ng/ml, P less than .01). Comparison of p.o. and i.v. imipramine doses indicated no difference in absolute bioavailability between the elderly and young of either sex. In contrast, after p.o. desipramine more limited age-related changes were noted. Desipramine half-life was slightly prolonged in elderly males (30.8 vs. 21.2 hr; P less than .05) apparently related to a nonsignificant decrease in p.o. clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Association between pore water sulfide concentrations and the distribution of mangroves

Abstract: At Humingbird Cay, Exuma, Bahamas, distributions of bothRhizophora mangle (red mangrove) andAvicennia germinans (black mangrove) are closely correlated with amounts of hydrogen sulfide (H2S) in the soil.R. mangle is primarily distributed within large areas of low to moderate H2S concentrations (mean= 40 mg/l). H2S levels underA. germinans are lower (mean = 22 mg/l), but the area immediately beyond their root zone often has extremely high sulfide concentrations (mean= 120 mg/l). These results suggest that past attempts to explain mangrove distribution in terms of monotonic soil gradients, the dispersal characteristics of propagules, and interspecific competition are incomplete, and that it will be necessary to examine the link between soil sulfur chemistry and mangrove distribution more fully.

Immunochemical similarities between monoclonal antibacterial waldenstrom’s macroglobulins and monoclonal anti-dna lupus autoantibodies

Abstract: Six monoclonal IgM from patients with Waldenstrom's macroglobulinemia that react with Klebsiella polysaccharides were tested for their ability to bind to nucleic acid antigens. One of the macroglobulins bound to the polynucleotide poly(G), and one bound to poly(G), poly(I), and single-stranded DNA. The reaction with the polynucleotides was specifically inhibited by the Klebsiella polysaccharide K30. A monoclonal lupus anti-DNA antibody (16/6) was found to react weakly with the Klebsiella polysaccharides K30 and K21. Five of the Waldenstrom macroglobulins shared an idiotypic determinant with the 16/6 anti-DNA antibody. The reaction between the macroglobulins and the antiidiotype serum was specifically inhibited by Klebsiella polysaccharides, an indication that the idiotypic marker was in the antigen-binding site of the macroglobulins. These results indicate the existence of widely dispersed conserved variable region genes that encode idiotypically related immunoglobulins with the capacity to bind to both bacterial polysaccharides and nucleic acids. Such genes can be expressed by patients with either Waldenstrom's macroglobulinemia or systemic lupus erythematosus.