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Biomedical subjects

C Lowe

Publications and source records attributed to C Lowe.

At least 55 records · Page 3Linked to original sources

The biological properties of bovine parathyroid hormone (1-41), a fragment generated from the native hormone by human leukocytes.

Native bovine parathyroid hormone (bPTH) was found to be readily cleaved with human leukocyte elastase to yield the fragments bPTH(1-41) and bPTH(42-84). These were then isolated by reverse-phase HPLC and characterised by gas-phase sequencing and amino acid analysis. The biological activities of these fragments were assessed in an adenylate cyclase bioassay using the rat osteosarcoma cell line UMR106. bPTH(1-41) was found to have approximately twice the molar potency of the native hormone from which it was derived. bPTH(42-84) had no biological activity and did not modulate the adenylate cyclase response to these cells to the native hormone. The possible physiological significance of these observations is discussed.

Adenylyl Cyclases↗

Adoptive cell transfer of resistance to Mycobacterium leprae infections in mice.

Cells were transferred from mice intradermally vaccinated with killed Mycobacterium leprae to sublethally irradiated recipients. Unseparated cells from lymph nodes or spleens of M. leprae vaccinated mice were found to cause significant inhibition of the growth of a subsequent M. leprae challenge in mouse footpads for up to 26 weeks after vaccination. Vaccination with live BCG and cells transferred from BCG-vaccinated mice caused no significant inhibition of M. leprae growth in mouse footpads. Cell separation into fractions containing predominantly B and T lymphocytes showed that the inhibition of growth was due to M. leprae-sensitized T lymphocytes. M. leprae vaccinated mice were also skin tested with soluble M. leprae antigen and showed maximum delayed hypersensitivity responses 4 weeks after vaccination.

Animals↗

Phenolic glycolipid 1 of Mycobacterium leprae causes nonspecific inflammation but has no effect on cell-mediated responses in mice.

The involvement of the phenolic glycolipid from Mycobacterium leprae in cell-mediated immunity has been investigated in this study. The phenolic glycolipid itself does not appear to stimulate cell-mediated immunity directly, as shown by its failure to elicit a classical delayed-type hypersensitivity response in mice immunized with M. leprae or to stimulate M. leprae-immune lymph node cells in a lymphoproliferative assay. Intradermal vaccination with the phenolic glycolipid failed to influence the growth of M. leprae in mouse footpads. A nonspecific inflammatory response to the sonicated glycolipid was observed in mice vaccinated with whole M. leprae and in control animals. No evidence was obtained for any adjuvant or suppressive effect on cell-mediated immunity by the phenolic glycolipid either to M. leprae or an unrelated antigen (sheep erythrocytes); neither sensitization nor elicitation to either antigen was affected.

Adjuvants, Immunologic↗

Monosodium glutamate exposure in the neonate alters hypothalamic and pituitary neuropeptide levels in the adult.

Administration of monosodium glutamate (MSG) during the neonatal period in rats produced differential effects on the contents of various neuropeptides in the hypothalamus: beta-endorphin (beta-E) level was reduced by 70% while substance P (SP), neurotensin (NT) and Met5-enkephalin (ME) levels were not significantly changed (ME content of male rats was slightly reduced). The contents of ME, SP and NT in striatum and hippocampus were also unaffected by the same treatment. Male rats contain higher pituitary content of beta-endorphin-like immunoreactivity (beta-ELI) than female rats. MSG treatment reduced the pituitary content of beta-ELI and abolished the sex difference in beta-ELI level seen in the control rats. MSG treatment in the neonates by eliminating beta-E neurons while sparing ME neurons in the brain may be a useful tool for studying the different functions of these two separate opioid peptides.

Animals↗

Sequential effects of acute meconium obstruction on pulmonary function.

The relationship between pulmonary function and the migration of meconium to distal airways was determined in 10 rabbits (mean weight 2.6 kg) after insufflation of a meconium-saline mixture (1--2 ml/kg). Animals were anesthetized, cannulated, intubated, and mechanically ventilated with 100% oxygen. Lung mechanical dysfunction was most severe during the early phase of meconium migration, 15 min postinsufflation. Substantial increases in inspiratory lung resistance (RI) and expiratory lung resistance (RE) suggest that the site of obstruction at 15 min was the large airways. A decrease in dynamic lung compliance with unchanged static compliance characterizes the obstruction as partial. At 15 min and throughout the migration process, RE was greater than RI, demonstrating a check-valve effect. This phenomenon was substantiated by an increased functional residual capacity (FRC) in all rabbits, presumably due to gas trapping. Secondary to these changes, marked hypoxemia, hypercapnea, and acidosis developed in spite of assisted ventilation with 100% oxygen. At 60 and 120 min postinsufflation, both RI and RE decreased as compared to 15 min. This suggests that the predominant site of obstruction shifted to medium and small airways concomitant with the migration of meconium. Widespread and uneven distribution of meconium still produced significant frequency dependence of lung compliance. Static compliance remained unchanged, indicating that meconium does not affect surface-active or tissue properties of the lung within 120 min postinsufflation. These data suggest that effective respiratory management after meconium aspiration is dependent on the degree of meconium migration, as reflected by pulmonary mechanics.

Airway Obstruction↗

Effect of purification steps on the immunogenicity of Mycobacterium leprae.

In studies aimed at the development of an antileprosy vaccine for use in man, Mycobacterium leprae suspensions were prepared from livers of experimentally infected armadillos. The 2 methods of purification in chief use, carried out after irradiation of the tissue with 2.5 megarads of gamma irradiation from 60Co, involved treatment with 0.1N NaOH for 2 h at room temperature, trypsin and chymotrypsin digestion for 24h at 37 degrees, and separation in a 2-phase liquid polymer (dextran:polyethylene glycol) system. All vaccines were autoclaved and injected intradermally in mice. Earlier studies have shown that heat inactivation does not interfere with the immunogenicity of M. leprae. Immunogenicity was measured by foot-pad enlargement (FPE) after challenge with heat-killed M. leprae suspensions or by protection against infectious foot-pad challenge. The results indicated that the irradiation and 2-phase separation did not decrease immunogenicity but the NaOH treatment and enzyme digestion did.

Animals↗

Plasmapheresis and lymphoplasmapheresis in the management of rheumatoid arthritis.

We have demonstrated the efficacy of therapeutic pheresis in a number of rheumatic diseases, especially rheumatoid arthritis (RA). Ten of 12 patients with RA went into remissions averaging 4 months. These patients were pheresed 20 times over 11 weeks in a tapering fashion on a Haemonetics Model 30 Blood Processor. Clinical remissions were sustained even though serologies, immunoglobulins, immune functions, sedimentation rates, and circulating immune complexes returned to their pre-pheresis baseline by pheresis number 20. All these patients were taking gold or D-penicillamine concurrently, but neither of the 2 patients who failed to respond was on these agents. Plasmapheresis was just as effective as lymphoplasmapheresis. It is theorized that removal of a plasma factor that modulates lymphocyte or neutrophil function produces remissions in RA and that long-acting drugs (e.g., gold or penicillamine) are able to prevent its continued production and produce a sustained remission.

Adult↗

Liquid ventilation: cardiovascular adjustments with secondary hyperlactatemia and acidosis.

Cardiovascular adjustments during liquid ventilation were investigated in seven cats. Cardiac output (CO) and regional blood flow were measured with radioactive microspheres during both spontaneous air breathing (control) and ventilation with fluorocarbon liquid, FC-80. CO was found to decrease 48% (P less than 0.05) during liquid breathing as compared to control. This decrease largely reflected a reduced stroke volume. Despite the decreased CO, mean arterial pressure remained unchanged, indicating a 48% increase (P less than 0.002) in total peripheral resistance (TPR). Secondary to the reduced CO and increased TPR, extensive redistribution of blood flow occurred during liquid ventilation. The arterial lactate concentration and lactate-to-pyruvate ratio (L/P) were significantly increased (P less than 0.02). Furthermore, the increase in L/P correlated with the decrease in CO (r = 0.70; P less than 0.01). In turn, the significant decrease in pH during liquid breathing was found to correlate with the increase in L/P (r = 0.85; P less than 0.001). These data clearly demonstrate signficant alterations in cardiovascular dynamics during liquid ventilation with secondary hyperlactatemia and acidosis.

Animals↗

Long-term plateletpheresis in the management of primary thrombocytosis.

We attempted to control the platelet count of a patient with primary thrombocytosis utilizing long-term plateletpheresis therapy. The patient previously could not be controlled with chemotherapy, because of rapid development of leukopenia. Although intensive pheresis at the rate of four to five procedures per week produced rapid lowering of the patient's platelet count, continued therapy at the rate of two to three procedures a week failed to maintain these counts, and platelets gradually rose to pretreatment levels. We conclude that while plateletpheresis can produce acute lowering of elevated platelet counts, the rate of platelet production in primary thrombocytosis may be too rapid to allow for long-term control by pheresis alone, utilizing an acceptable treatment schedule of one of three procedures per week.

Blood Transfusion↗

Use of long-term leukapheresis in the treatment of chronic lymphocytic leukemia.

We used repeated leukapheresis in the long-term management of chronic lymphocytic leukemia. Twelve patients with far-advanced disease that was refractory to standard forms of therapy, were studied. Six patients completed a predefined course of therapy. Although a single patient responded favorably for a period of time, no other patient was benefited by this treatment. While circulating lymphocyte counts in these patients always could be reduced, generally, this was not associated with improvements in pancytopenia, hypogammagobulinemia, adenopathy, organomegaly, or constitutional symptoms of lethargy, fevers and night sweats. Mean survival was only ten months from onset of therapy. We conclude that long-term leukapheresis is ineffective in the management of far-advanced chronic lymphocytic leukemia.

Agammaglobulinemia↗