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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 523 records · Page 29Linked to original sources

Long-acting gonadotropin hormone-releasing hormone analog used to treat uteri.

Because the size of leiomyomata uteri often decreases significantly after menopause, the authors elected to employ a long-acting gonadotropin hormone-releasing hormone analog (GnRH-alpha) (imbzl-D-His6-Pro9-Net-GnRH) to create a state of pseudomenopause in six patients with leiomyomata uteri diagnosed on the basis of pelvic examination and confirmed by pelvic ultrasonography. Patients received daily, subcutaneous injections of GnRH-alpha (4 micrograms X kg-1 X 24 hour-1) for 6 months. Uterine size (13.8 +/- 4 weeks [mean +/- standard deviation (SD), n = 6]) was determined by pelvic examination and uterine volume (533.9 +/- 394 ml [mean +/- SD, n = 6]) was determined by pelvic ultrasonography before medical therapy was begun. They observed a decrease in uterine size by pelvic examination within 4 weeks of the initiation of therapy, and all patients experienced a decrease in uterine size (9.5 +/- 4 weeks [mean +/- SD, n = 6]) (P less than 0.05) within 8 weeks of initiation of therapy. After 6 months of therapy, uterine size was 229.5 +/- 145 ml (mean +/- SD, n = 6). During treatment, plasma estrogen concentrations were assessed intermittently (every 1 to 4 weeks) and remained less than 4 pg X ml-1 throughout the period of therapy. All six patients have discontinued therapy. There has been no increase in uterine size in these patients for a period from 3 to 7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

An in vitro investigation of the intracellular bioactivity of amoxicillin, clindamycin, and erythromycin for Staphylococcus aureus.

The intraphagocytic bioactivities for Staphylococcus aureus of amoxicillin, clindamycin, and erythromycin (0.0075-20 micrograms/ml) were measured in human polymorphonuclear leukocytes (PMNLs) with the combination of a fluorochrome microassay and a radioassay. PMNLs with normal or depleted membrane-associated oxidative metabolism were used to investigate the interactions that may occur between the intrinsic O2-dependent antimicrobial systems of human phagocytes and antimicrobial agents in the elimination of intracellular microbial pathogens. Neutralization of O2-dependent antimicrobial systems with retention of phagocytic capacity was achieved with use of PMNLs from four children with chronic granulomatous disease (CGD) or NaF-pulsed normal PMNLs. None of the test antibiotics possessed intracellular bactericidal activity. Clindamycin and erythromycin possessed significant intracellular bacteriostatic activity relative to the modest activity of amoxicillin. Optimal intracellular bioactivity of all three antibiotics was obtained with normal PMNLs relative to NaF-pulsed or CGD PMNLs, a result indicating the existence of beneficial interactions between the antimicrobial agents and the O2-dependent antimicrobial systems of PMNLs.

Amoxicillin↗

An in-vitro study of oral therapeutic doses of co-trimoxazole and erythromycin stearate on abnormal polymorphonuclear leucocyte migration.

The effects of administration for four days of co-trimoxazole (2 X 500 mg tablets daily) and erythromycin stearate (3 X 500 mg tablets daily) on persistently abnormal polymorphonuclear leucocyte (PMNL) migration in six individuals with a history of chronic or recurrent bacterial infections were studied. The effects of co-incubation of PMNL in vitro with both antimicrobial agents at concentrations of 12(-5) and 10(-4) M were also investigated. Two different leucoattractants were used, autologous serum activated with bacterial endotoxin (EAS) and the synthetic chemotactic tripeptide FMLP. In three homosexual males with the acquired immunodeficiency syndrome (AIDS) abnormal PMNL motility was associated with the presence of serum inhibitor(s) of cell migration. In a fourth female subject, with recurrent episodes of acute periodontitis, and intrinsic cellular defect of PMNL migration associated with markedly impaired FMLP-induced degranulation and binding to PMNL was observed. In the remaining two subjects with chronic osteomyelitis, the precise abnormality of PMNL movement was not defined but appeared to be of the cellular intrinsic type. Co-incubation of PMNL with erythromycin, but not cotrimoxazole, at both concentrations tested (10(-5) and 10(-4) M) significantly improved cell migration to EAS, Likewise administration of erythromycin, but not cotrimoxazole, significantly improved PMNL migration to EAS. Improvement or correction of abnormal PMNL motility during antimicrobial chemotherapy with erythromycin may be a useful property of this antimicrobial agent.

Acquired Immunodeficiency Syndrome↗

Translational control in murine hepatitis virus infection.

High multiplicity infection of mouse fibroblast L-2 cells with mouse hepatitis virus (MHV) resulted, within 6 h, in a decline in total protein synthesis to about 7% of that observed in uninfected cells. The amount of intracellular total translatable RNA, however, increased approximately threefold, as a result of the accumulation of virus-encoded mRNAs. MHV-infected cells could be superinfected with vesicular stomatitis virus, demonstrating that MHV infection did not irreversibly alter the cellular translational machinery to the exclusion of non-MHV mRNAs. Comparative polysome analysis from MHV-infected and uninfected L-2 cells showed that MHV infection resulted in an increase in single 80S ribosomes and in a shift from longer to shorter polysomes. These observations suggest first, that MHV infection inhibits total protein synthesis at a very early stage, as evidenced by the increase in 80S ribosomes, and, second, that the increased number of viral mRNAs produced after infection compete with cellular mRNAs for cellular ribosomes. In vitro translation of RNA extracted from MHV-infected and mock-infected cells suggested that levels of cellular mRNAs were decreased after infection. This suggestion was confirmed by demonstrating the loss of cellular actin mRNA, using a radiolabelled cDNA probe, as a consequence of MHV infection.

Animals↗

Potentiation of the generation of reactive oxidants by human phagocytes during exposure to benoxaprofen and ultraviolet radiation in vitro.

The effects of ultraviolet (UV) radiation on the spontaneous membrane-associated oxidative metabolism of human polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (MNL), co-incubated in the presence and absence of the non-steroidal, anti-inflammatory drug (NSAID) benoxaprofen at various concentrations, were investigated in vitro. Assays of superoxide generation and luminol-enhanced chemiluminescence (CL) were used to detect the production of reactive oxidants by PMNL and MNL. Benoxaprofen in the absence of UV radiation caused a dose-related activation of superoxide production and CL by PMNL. Exposure of PMNL to UV radiation in the absence of benoxaprofen caused a slight increase in superoxide generation and an unsustained slight increase in CL within 10 s. Exposure of both MNL and PMNL to UV radiation in the presence of benoxaprofen had a marked synergistic effect on both superoxide generation and CL. These effects were also achieved with UVA irradiation but were not detected when adherent cell depleted MNL or sodium fluoride (NaF) (10-2 M) pulsed PMNL, or PMNL from children with chronic granulomatous disease, were used. The pro-oxidative effects of benoxaprofen and UV radiation alone and in combination are dependent on intact phagocyte membrane-associated oxidative metabolism. It is postulated that the pro-oxidative interactions which occur between human phagocytes, benoxaprofen and ultraviolet radiation cause the dermatological side-effects of benoxaprofen.

Anti-Inflammatory Agents↗

Uptake and autoreceptor-controlled release of [3H]-GABA by the hypothalamic median eminence and pituitary neurointermediate lobe.

The uptake and release of gamma-[3H]-aminobutyric acid ([3H]-GABA) by the median eminence and the neurointermediate lobe of the pituitary was investigated using sucrose homogenates as crude synaptosomal preparations. Uptake in both areas showed predominantly neuronal specificity and similar Km values, but the median eminence had a considerably greater Vmax value. Release of [3H]-GABA could be stimulated by elevated K+ concentrations, in a Ca2+-dependent manner. Stimulated release was reduced by muscimol, implying the existence of presynaptic autoreceptors in both areas. A number of other transmitters and peptide hormones were demonstrated to have no effect on stimulated release of [3H]-GABA in either area.

Animals↗

CRP and neutrophils: functional effects and complex uptake.

The uptake of C-reactive protein (CRP)-pneumococcal C-polysaccharide (CPS) complexes by neutrophils was studied. A specific CRP dependent mechanism of uptake was demonstrated. This promoted CPS (complexed to CRP) clearance which was further enhanced by additional complement activation. Physiological concentrations of low density lipoprotein inhibited entry of complexed CPS into neutrophils but had no effect on entry of CRP alone. Pure human CRP was shown to have no effect on neutrophil chemotaxis and oxidative metabolism.

Adult↗

An objective filter-based, enzymatic method for the in vivo measurement of the migration of human polymorphonuclear leucocytes.

Incorporation of control valves into a previously described device enabled us to regulate the formation of 8 suction blisters on the upper surface of the forearm in adult human volunteers. After the removal of the raised epidermis and blister fluid, uniform areas of denuded dermis were obtained by placing hollow adhesive ring reinforcers onto each of the regions of exposed dermis. Single or double nitrocellulose filters were then placed onto each of the areas of moistened, exposed dermis. The chemotactic tripeptide FMLP was incorporated into 1% agarose containing 0.1% bovine serum albumin (BSA) to give a concentration range of 10(-8) M to 10(-6) M FMLP. In control systems the FMLP was omitted. Cylindrical agarose blocks +/- FMLP were then placed onto the filters and encased in individual perspex cups glued firmly onto the skin. The filter(s) and agarose blocks were replaced at 2 h intervals and polymorphonuclear leucocyte (PMNL) migration onto (single filter) and into (double filter) the filters was measured by microscopic enumeration or according to the amount of myeloperoxidase (MPO) and lysozyme in the supernatants of filters immersed in 0.1% Triton-X for 10 min to lyse the PMNL. Microscopic enumeration was found to be unsuitable but the method based on MPO and lysozyme release from filter-associated PMNL was rapid, accurate and reproducible. Detectable PMNL migration (greater than 90%) occurred at 3-4 h and was maximal at 8-10 h. This pattern was observed for both the control and FMLP-containing systems. However, PMNL migration was significantly greater in FMLP-exposed dermis. FMLP at 10(-6) M was found to promote maximal PMNL migration. Significantly greater MPO and lysozyme activities were observed with the double filter system. This method is suitable for the objective quantitation of PMNL migration in vivo.

Adult↗

Structure of a novel phosphoglycolipid from Deinococcus radiodurans.

The chemical structure of a major phosphoglycolipid from Deinococcus radiodurans has been shown to be 2'-O-(1,2-diacyl-sn-glycero-3-phospho)-3'-O-(alpha-galactosyl)-N-D-gl yceroyl alkylamine. By infrared spectroscopy, the lipid was shown to contain both carbonyl ester and amide linkages. Chemical analysis demonstrated a molar ratio of fatty acid, carbohydrate, and phosphorus of 2:1:1. The lipid was shown to contain an sn-3-phosphatidic acid backbone by digestion with phospholipase A2. Phosphodiester bond cleavage of the lipid with hydrofluoric acid liberated a component which contained galactose, glyceric acid, and alkylamines. Using NMR and permethylation/hydrolysis procedures, galactose was shown to be linked alpha-glycosidically to the 3-O-position of glyceric acid.

Chemical Phenomena↗

Effects of GABA receptor agonists on [3H]dopamine release from median eminence and pituitary neurointermediate lobe.

The effects of GABAA and GABAB receptor agonists were examined on stimulus-induced release of [3H]dopamine ([3H]DA) from a synaptosomal preparation of median eminence (ME) and pituitary neurointermediate lobe (NI). Muscimol was found to inhibit [3H]DA release from ME in a bicuculline-sensitive, strychnine-insensitive manner, but had no effect in NI. Homocarnosine also inhibited [3H]DA release from ME. Baclofen had no effect in either area. These results demonstrate an interaction between two putative prolactin release inhibitory factors, DA and GABA, at the site of secretion into hypophysial portal blood.

Animals↗

A comparison of the effects of tobramycin and netilmycin on the functions of human polymorphonuclear leucocytes and lymphocytes in vitro and in vivo.

The effects of the antimicrobial agents tobramycin and netilmycin on the functions of human polymorphonuclear leucocytes (PMNLs) and on the mitogen-induced transformation of lymphocytes have been investigated both in vitro and in vivo before and 1 hour after a single intramuscular injection of the antibiotics. Neither antibiotic affected the migratory, phagocytic or antimicrobial capacities of PMNLs or the proliferative responses of lymphocytes to mitogens, at therapeutic concentrations or at 10-100-fold greater than therapeutic concentrations. Likewise, no alterations in these leucocyte functions accompanied the intramuscular injection of either antibiotic. neither tobramycin nor netilmycin therefore interferes with host immunodefence mechanisms.

Adult↗