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Biomedical subjects

J Connor

Publications and source records attributed to J Connor.

At least 91 records · Page 5Linked to original sources
PubMed1986

Antimicrobial activity of various immunomodulators: independence from normal levels of circulating monocytes and natural killer cells.

The effects of 89Sr treatment on the natural host resistance of CD-1 mice and the enhancement of resistance by immunomodulators to infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV-2) were determined. In the CD-1 mouse, single-dose treatment with 89Sr caused a profound decrease in the number of circulating monocytes (Mo), lymphocytes, and polymorphonuclear leukocytes (PMN) within 1 week. There was also marked functional impairment of the Mo inflammatory response, as well as markedly decreased spontaneous and activatable cytotoxicity by splenic natural killer (NK) cells. Despite this profound cellular suppression, there was no significant change in natural resistance of CD-1 mice to L. monocytogenes or HSV-2 infection. Furthermore, prophylactic treatment of mice with the biologic immunomodulator Corynebacterium parvum or the synthetic immunomodulators maleic anhydride-divinyl ether or avridine in liposomes resulted in comparable enhancement of resistance in 89Sr-treated and normal mice. These data indicate that natural and immunomodulator-enhanced resistance of CD-1 mice to microbial infections do not depend on normal levels of Mo, PMN, or NK cells. The resistance enhancement may rely on activated tissue macrophages (M phi). In contrast to the early changes in circulating leukocytes, the resident peritoneal cell populations were not markedly altered until after day 30. There then was a distinct decline in lymphocytes and a gradual decline in M phi; the change in M phi was apparently due to the lack of an age-related increase in the peritoneal M phi population in 89Sr-treated mice in comparison with a slight increase in resident M phi in normal mice. After CD-1 mice were treated with 89Sr, the number of PMN and the function of NK cells generally recovered by about day 50 and was followed by partial recovery of circulating Mo, unless a second dose of 89Sr was administered.

Animals↗
PubMed1986

pH-sensitive immunoliposomes as an efficient and target-specific carrier for antitumor drugs.

pH-sensitive immunoliposomes composed of dioleoylphosphatidyl-ethanolamine and oleic acid (8:2) significantly enhanced the cytotoxic effect of the entrapped drug 1-beta-D-arabinofuranosylcytosine (ara-C) to target L-929 cells, as compared to free drug, drug encapsulated in antibody-free liposomes, or in pH-insensitive immunoliposomes. These pH-sensitive immunoliposomes were ineffective against nontarget A-31 cells. The enhanced cytotoxic effect could be blocked by excess free antibody or excess drug-free immunoliposomes. Pretreatment of target cells with the weak bases chloroquine or NH4Cl, which raise the internal pH of cellular acidic organelles such as endosomes and lysosomes, inhibited the cell killing activity of ara-C encapsulated in the pH-sensitive immunoliposomes. Since it is known that ara-C is rapidly inactivated in the lysosomes, our results suggest that the release of ara-C from the pH-sensitive immunoliposomes occurs in a prelysosomal compartment, i.e., the endosome. Parallel experiments using methotrexate as a cytotoxic drug confirm the enhanced ability of the pH-sensitive liposomes for cytoplasmic drug delivery over that of free drug. These results indicate that pH-sensitive immunoliposomes can be used as an efficient and target-specific carrier for antitumor drugs.

Animals↗
PubMed1985

Efficient cytoplasmic delivery of a fluorescent dye by pH-sensitive immunoliposomes.

We previously showed that liposomes composed of dioleoylphosphatidyl-ethanolamine and palmitoyl-homocysteine (8:2) are highly fusion competent when exposed to an acidic environment of pH less than 6.5. (Connor, J., M. B. Yatvin, and L. Huang, 1984, Proc. Natl. Acad. Sci. USA. 81:1715-1718). Palmitoyl anti-H2Kk was incorporated into these pH-sensitive liposomes by a modified reserve-phase evaporation method. Mouse L929 cells (k haplotype) treated with immunoliposomes composed of dioleoylphosphatidylethanolamine/palmitoyl-homocysteine (8:2) with an entrapped fluorescent dye, calcein, showed diffused fluorescence throughout the cytoplasm. Measurements by use of a microscope-associated photometer gave an approximate value of 50 microM for the cytoplasmic calcein concentration. This concentration represents an efficient delivery of the aqueous content of the immunoliposome. Cells treated with immunoliposomes composed of dioleoylphosphatidylcholine (pH-insensitive liposomes) showed only punctate fluorescence. The cytoplasmic delivery of calcein by the pH-sensitive immunoliposomes could be inhibited by chloroquine or by incubation at 20 degrees C. These results suggest that the efficient cytoplasmic delivery involves the endocytic pathway, particularly the acidic organelles such as the endosomes and/or lysosomes. One possibility is that the immunoliposomes fuse with the endosome membranes from within the endosomes, thus releasing the contents into the cytoplasm. This nontoxic method should be widely applicable to the intracellular delivery of biomolecules into living cells.

Animals↗
PubMed1984

Genesis of Kirsten murine sarcoma virus: sequence analysis reveals recombination points and potential leukaemogenic determinant on parental leukaemia virus genome.

The genome of Kirsten murine sarcoma virus was formed by recombination between Kirsten murine leukaemia virus sequences, and rat sequences derived from a retrovirus-like '30S' (VL30) genetic element encompassing the Kras oncogene. Using cloned DNAs we have determined the nucleotide sequences of the long terminal repeats and adjacent regions, extending across the points of recombination on the sarcoma and leukaemia virus genomes. Our results suggest that discrete regions of homology and other cryptic sequence features, may have constituted recombinational hot-spots involved in the genesis of the Kirsten murine sarcoma virus genome. We have also compared the sequence of the Kirsten murine leukaemia virus p15 env and adjacent long terminal repeat with the corresponding regions of the AKV and Gross A murine leukaemia virus genomes. This comparison has identified a leukaemogenic determinant in the U3 domain of the long terminal repeat, possibly within a enhancer-like sequence element.

Amino Acid Sequence↗
PubMed1984

Double-blind placebo-controlled trial of oral acyclovir in first-episode genital herpes simplex virus infection.

One hundred nineteen patients with primary and 31 patients with nonprimary first-episode genital herpes were treated for ten days with 200 mg of acyclovir capsules or placebo capsules orally five times daily. Among acyclovir recipients with primary genital herpes, the median duration of viral shedding (two days), time to crusting of all lesions (seven days), time to healing of all lesions (12 days), and duration of local pain (five days) and constitutional symptoms (three days) were shorter than among placebo recipients (9, 10, 16, 7, and 6 days, respectively). Among patients with nonprimary first-episode genital herpes, oral acyclovir shortened the median duration of viral shedding but had no significant effect on the duration of lesions or symptoms. The time to first recurrence and frequency of recurrences were similar in acyclovir- and placebo-treated patients. Oral acyclovir treatment of primary first-episode genital herpes shortens the duration of viral shedding and symptoms and accelerates healing, but it does not appear to influence subsequent genital recurrences.

Acyclovir↗
PubMed1984

Clinical study of mastitis-metritis-agalactia in sows in Illinois.

Mastitis-metritis-agalactia (MMA) occurred in 6.9% of 16,405 farrowings recorded over 1 year (1981) in 31 Illinois swine herds. Prevalence of MMA among herds ranged from 1.1% to 37.2% and was not correlated to herd size. There was a significant positive correlation between the prevalence of MMA and the housing system wherein sows were moved from pasture gestation to crates immediately before farrowing. A significant seasonal peak of MMA was found for the third quarter of the year (10.3%). Mean prevalence of MMA was 13% in pluriparous sows and 4.2% in primiparous sows. The difference was not significant. Sows with MMA gave birth to more live pigs per litter compared with healthy sows (+0.7 pigs per litter). The number of stillbirths and pigs found dead after birth also was higher in sows with MMA (+4.6%). Total pig mortality until 1 week of age was 56% in litters of pluriparous sows with MMA and 17% in litters of healthy pluriparous sows and, respectively, 41% and 15% in litters of primiparous sows. The mean number of pigs per litter surviving at 1 week of age was 5.6 in pluriparous sows with MMA and 9.3 in healthy sows and, respectively, 6.2 and 8.3 in primiparous sows. For all herds investigated, mean litter size at birth (including stillbirths) was 11.0. Total pigs mortality until 1 week of age was 31%. Pig losses attributable to MMA, at 6.9% prevalence of the disease, were 4% of all pigs born and 12.9% of the pig mortality until 1 week of age.

Age Factors↗
PubMed1984

Unusual long terminal repeat sequence of a retrovirus transmissible mouse (VL 30) genetic element: identification of functional domains.

We have determined the nucleotide sequence and mapped the transcriptional boundaries in the long terminal repeats (LTRs) and adjacent regions of a retrovirus transmissible virus-like 30S ( VL30 ) mouse genetic element. The 572 base pair LTRs contain transcriptional regulatory sequences and are bounded by short imperfect repeats, with a minus strand tRNAgly primer binding site and a purine rich plus strand primer site flanking each of their inner boundaries. The 3' end of each LTR consists of an extensive 80 base pair redundancy of tRNA primer site and inverted repeat sequences while 41 and 47 base pair imperfect tandem repeats are present between the 5' capping site and the putative polyadenylation signal. Comparison with other retrovirus-like LTR sequences suggests possible modes of recombination that could occur between VL30 and other genetic elements.

Animals↗
PubMed1984

pH-sensitive liposomes: acid-induced liposome fusion.

Sonicated unilamellar liposomes containing phosphatidylethanolamine and palmitoylhomocysteine fuse rapidly when the medium pH is lowered from 7 to 5. Liposome fusion was demonstrated by (i) mixing of the liposomal lipids as shown by resonance energy transfer, (ii) gel filtration, and (iii) electron microscopy. The pH-sensitive fusion of liposomes was observed only when palmitoylhomocysteine (greater than or equal to 20 mol%) was present in the liposomes. The presence of phosphatidyl-ethanolamine in the liposomes greatly enhanced fusion whereas the presence of phosphatidylcholine inhibited fusion. During fusion of liposomes containing phosphatidylethanolamine and palmitoylhomocysteine (8:2, mol/mol), almost all of the encapsulated calcein was released. Inclusion of cholesterol (40 mol%) in the liposomes substantially decreased leakage without impairing fusion.

Homocysteine↗
PubMed1984

Light- and voltage-dependent increases of calcium ion concentration in molluscan photoreceptors.

Changes in cytoplasmic calcium levels have been measured in photoreceptors from Hermissenda crassicornis using the indicator dye Arsenazo III. Following stimulation with light, the dye absorbance, measured at the Ca-sensitive wavelength pair 660-690 nm increased and remained elevated for 10s of seconds. The absorbance change began during the initial part of the photodepolarization, but the early time course was obscured by the stimulus flash. Absorbance at a second wavelength pair, 630-690 nm, changed only a small amount during the photoresponse. This wavelength dependence of the dye absorbance was the same as that observed for direct Ca injections into larger Hermissenda neurons. Pairing the light stimulus with depolarizing current (0.5 nA) increased the dye absorbance, while sufficient hyperpolarizing current (0.5-1 nA) markedly reduced the dye response to a paired light flash. Depolarizing current alone gave a small, slowly rising dye absorbance change. Light- and current-induced dye absorbance change was greatly reduced by external Cd. We conclude that light stimulus causes an increase in cytoplasmic Ca, which is accentuated by extrinsic depolarizing input, and that most of the increase results from transmembrane influx.

Animals↗
PubMed1975

Electrical characteristics of frog atrial trabeculae in the double sucrose gap.

The electrical behavior of small single frog atrial trabeculae in the double sucrose gap has been investigated. The currents injected during voltage clamp experiments did not behave as predicted from the assumption of spatial uniformity of the voltage across a Hodgkin-Huxley membrane. Much of the difference is due to the geometrical complexities of this tissue. Nonetheless, two transient inward currents have been identified, the faster of which is blocked by tetrodotoxin (TTX). The magnitude of the slower transient varies markedly between preparations but always increases in a given preparation with increase of external calcium. The fast transient current traces, at small to intermediate depolarizations, are often marred by the presence of notches and secondary peaks due most probably to the loss of space clamp conditions. In many preparations these could be removed by reducing the current magnitude through application of a partially-blocking dose of TTX. Conversely, in the preparations whose fast transient was fully blocked by TTX, notches and secondary peaks in the slow transient could by induced through increasing calcium concentration and thereby the slow current magnitude. Previously used techniques for the measurement of the reversal potential of the fast inward transient have been shown to be invalid. In so far as they can be measured, the reversal potentials of the fast and slow inward transient are in the same neighborhood, i.e. around 120 mV from rest. The true values may be quite a bit apart. The total charge flow in the capacitive transient was measured for different sized nodes and preparations. From these data and estimates of plasma membrane area per unit trabecular volume, specific membrane capacitances of around 3 muF/cm2 were calculated for small bundles. The apparent ion current densities on this basis are approximately 1/10 of those measured in axons. The capacitive current occurring in small bundles decayed as the sum of at least three exponential functions of time. On the basis of these data and the anomalously large stable node widths, we suggest a coaxial core model of the preparation with the inner elements in series with an additional large extracellular resistance.

Animals↗
PubMed1975

The pharmacology of Avena sativa.

The pharmacology of Avena sativa has been investigated in laboratory animals following a report that tincture of Avena sativa reduced the craying for cigarettes in man. The tincture, evaporated to dryness, craving for cigarettes in man. The tincture, evaporated to dryness, re-constituted in an equal volume of water and administered by stomach tube or intraperitoneal injection, antagonized the antinociceptive effect of morphine in two separate test (hot-plate and tail flick). Compared with animals made depedent on morphine alone, mice pretreated with repeated injections of morphine plus extract passed a smaller number of stools and tended to jump less after administration of nalorphine. The pressor response to intravenously administered nicotine in urethane-anaesthetized rats was also antagonized by prior administration of Avena sativa. However, the aqueous extract prepared from the tincture did not affect the seizure threshold to bemegride or nicotine or the sleeping time induced by barbitone sodium.

Animals↗
PubMed1973

Potentiation by endotoxin of responses associated with increases in calcium conductance.

Bacterial endotoxin at concentrations of 0.03 mug/ml enhanced the following responses, each of which reflects calcium influx: (1) contraction of spiral intestine retractor muscle of dogfish; (2) amplitude of postsynaptic potential of squid giant synapse as a function of presynaptic depolarization; (3) membrane responses of deep abdominal extensor muscle of crayfish, stimulated intracellularly; and (4) slow transient (calcium) current in trabeculae of frog atrium under voltage clamp. Corticosteroid antagonized the endotoxin effect on the smooth muscle, not on the frog atrial current. One mechanism of action of endotoxin may be to increase transmembrane calcium currents.

Action Potentials↗