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Biomedical subjects

J C Martin

Publications and source records attributed to J C Martin.

At least 163 records · Page 9Linked to original sources
PubMed1986

Simultaneous measurements of macrophage-induced cytostasis and cytotoxicity of EMT6 cells by flow cytometry.

Cytostasis and cytotoxicity as well as survival and growth of EMT6 cells following exposure to tumoricidal macrophages have been examined using multiparameter flow cytometry. Macrophages were resolved from tumor cells, and the number of surviving EMT6 cells at different interaction times was determined by adding, to each cell suspension, fluorescent latex particles the concentration of which was known and counting them along with the cells. The percentages of EMT6 cells in S phase were determined by analysis of DNA histograms and compared to the percentages as determined by autoradiography. The progression of cells through the cell cycle was also examined during exposure to macrophages by dual parameter analysis of DNA content and bromodeoxyuridine incorporated into DNA prior to exposure to macrophages. The results showed that, by 4 h of interaction with tumoricidal macrophages, EMT6 cells stopped progressing; tumor cell progression was inhibited in all phases of the cell cycle. By 24 h, there was an absolute decrease in survival. By 48 h, however, surviving tumor cells which escaped the tumoricidal activity of macrophages exhibited a population doubling rate similar to control cells.

Animals↗
PubMed1985

Active analog pipeline delays for high signal rates in multistation flow cytometers.

Flow cytometers with sequential measuring stations require alignment of event timing information to assure that multiparameter data for each cell are properly correlated. Information from the first detector must be delayed until signals are produced at the last detector, with adjustments to align them in time for simultaneous digitization after the last measurement is completed. By using an analog "pipeline" delay, the deadtime between the first and last measuring stations can be minimized. The described device is capable of acquiring and propagating many signals within the delay period, with good fidelity at high signal rates. An integrated circuit charge-coupled device (CCD), which is an analog shift register, is shown to be useful as a signal delay in the time range from 22 microseconds to several milliseconds.

Flow Cytometry↗
PubMed1985

Electrochemistry of purine derivatives. 2: Correlation of anodic differential pulse peak potentials with Hammett substituent constants.

Differential pulse voltammetry was used to measure anodic peak potentials at the glassy carbon electrode (in pH 2 to 11 aqueous buffer versus Ag/AgCl) for 14 purine bases and nucleosides. The tested compounds included the antiviral drugs 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (1) and acyclovir (2) plus six analogues of 1. At pH 7, representative peak potential values were as follows: 1, 0.97 V; 2, 1.01 V; 6-amino-6-deoxy-1 1.00 V; guanosine, 1.03 V; 2'-deoxyguanosine, 1.03 V. The observed potentials at pH 7 and related literature values correlated with Hammett pi(para) substituent constants. For 24 purines, stepwise multiple linear regression provided the relationship: P7 = (1.08 +/- 0.055) + (1.13 +/- 0.13) sigma 8 + (0.338 +/- 0.061)sigma(2 + 6) + (0.281 +/- 0.043)D (with n = 24, r2 = 0.930, CV = 11.1, and F = 88) where P7 is the pH 7 oxidation potential, the subscripts refer to purine ring substitution position, and D is an indicator variable for substitution at purine N9 by furanoside or glycoside analogue moieties. The observed relationship permits predictions of anodic peak potentials for other purines the substitution patterns of which are known.

Antiviral Agents↗
PubMed1985

Maternal barbiturate administration and offspring response to shock.

Gravid Sprague-Dawley-derived rats were injected SC twice daily with either 20 or 40 mg/kg pentobarbital sodium (PT), sodium phenobarbital (PH), or the same volume of the saline vehicle on days 9-21 of pregnancy. Pair-feeding was employed. Vital, developmental, and activity measures were obtained on the neonates and locomotor activity was measured from 3-10 months of age. Avoidance was measured sequentially in a shuttle box, and in an operant chamber beginning at 3 months of age. The PH-80 dams gained less weight over the gestational period, and PH-80 and PH-40 offspring had more neonatal deaths. These male offspring were hyperactive at maturity, and PH-80 rats were initially slower to escape experimenter-initiated shock. PT exposure caused transient neonatal and juvenile hyperactivity. PT rats performed more poorly on both the conditioned avoidance and Sidman shock schedules, and had significantly lower brain: body weight ratios at 1 year of age. All four drug groups outperformed the saline offspring on subject-initiated shock schedules (punishment). Sex of offspring was determined on postnatal day 4 and the sex ratio was shifted towards male births with both drugs relative to controls.

Animals↗
PubMed1985

Synthesis and antiherpes simplex virus activity of 9-[(1,3-dihydroxy-2-propylthio)methyl]guanine.

The synthesis of the thio analogue (thio-DHPG, 2) of 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 1) is described. The synthesis of 2 proceeded via the condensation of acetoxymethyl sulfide 9 with diacetylguanine 10 to give the protected nucleoside analogue 11. Although catalytic hydrogenolysis failed, the benzyl ether functionalities of 11 were successfully cleaved by an acetolysis reaction to furnish 14. Ammonolysis of 14 gave 2, which was also transformed to sulfoxide 15 and sulfone 16. Preliminary in vitro screening indicated that 2 exhibited comparable activity to DHPG against herpes simplex virus type 1 (HSV-1) but was less active against the type 2 virus (HSV-2) and human cytomegalovirus (HCMV). In a mouse encephalitis model (HSV-2), subcutaneous treatment with 2 led to a 53% reduction in mortality at a dose of 100 mg/kg per day.

Acyclovir↗
PubMed1985

Acyclic analogues of 2'-deoxynucleosides related to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine as potential antiviral agents.

A series of acyclic analogues of 2'-deoxynucleosides related in structure to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 1) have been synthesized and evaluated for antiviral activity against herpes simplex virus type 1 (F strain). Additionally, the ability of these analogues to function as substrates for the virus-specified thymidine kinase was examined. Phosphorylation by this kinase is essential for antiviral activity. Although the acyclic 4-oxopyrimidine nucleosides were substrates for the kinase, they were devoid of antiviral activity. In the purine series, most analogues similar in structure to DHPG did exhibit significantly lower antiviral activity, indicating that even small modifications in the purine substituents substantially reduce the antiviral potency. The most active agent, 2,6-diaminopurine 27, was only poorly phosphorylated by the viral kinase; therefore, its activity was most likely due to a prior enzymatic deamination to give DHPG. Evaluation of 27 in a mouse encephalitis model has shown it to be nearly as potent as DHPG (1).

Acyclovir↗
PubMed1985

Amplified flow-cytometric separation-free fluorescence immunoassays.

An equilibrium-type competitive-binding fluorescence immunoassay with high sensitivity and excellent precision is described that obviates separation of free from bound label. In the assay relatively large (10 microns diameter) antibody-coated non-fluorescent particles and very small (0.10 micron diameter) antigen-coated fluorescent latex particles are used. Soluble nonlabeled antigen competes with antigen on the microspheres for antibody binding sites on the larger spheres. After equilibrium is attained, the fluorescence distribution of 5000 of the large spheres is measured in a flow cytometer. The mean values for the fluorescence distribution obtained from samples containing known concentrations of soluble antigen are used to construct a standard displacement curve. In a prototype assay for the antigen horseradish peroxidase, a sensitivity of 10(-12) mol/L has been achieved. Undiluted serum can be assayed without loss of sensitivity. Preliminary experiments also indicate that double-antibody "sandwich"-type assays of very high sensitivity (10(-14) mol/L) are also possible when this dual-sphere concept is exploited.

Binding, Competitive↗
PubMed1984

[Tracheal stenosis in the cat: anatomopathologic repercussions on the pulmonary parenchyma].

A calibrated stenosis of the trachea was performed in 6 young cats and 1 old one (TS cats); the animals were observed for 8 or 15 weeks thereafter. The percentage of macrophages in bronchoalveolar lavage fluid was greater in the TS cats than in the controls. An irregular distribution of pulmonary lesions was found. 4 TS cats presented with a real emphysema with tracheobronchial inflammation, a parenchymatous infection which was histologically shown or quantified in lavage fluid (Haemophilus (10(8]. They exhibited episodes of hypoventilation which followed in quick succession. The alveolar section of the TS emphysematous lung was equal or greater (up to 88% of the lung surface observed) than that of both the same-aged controls (81.5%) and of an old emphysematous cat (88 months). The alveoli were more homogeneous (lower deviation). TS lung was characterized by a higher amount of dry tissue protein but hydroxyproline varied individually. A possible synergy between infection and ventilatory obstruction may be a tentative explanation for the etiogeny of this emphysema which appears to be secondary to tracheal stenosis.

Airway Obstruction↗
PubMed1983

Condensed form of (dG-dC)n X (dG-dC)n as an intermediate between the B- and Z-type conformations induced by sodium acetate.

Circular dichroism and laser Raman spectroscopy reveal that the synthetic DNA polymer (dG-dC)n X (dG-dC)n undergoes a cooperative transition induced by sodium acetate from a right-handed B-form to a left-handed Z-type conformation with a midpoint at 2.05 M. However, at concentrations only slightly higher than the end point of this transition (above approximately 2.2 M) and up to approximately 2.65 M, the Z-form is not stable in solution but aggregates to form highly condensed DNA. A manyfold increase of positive ellipticity in the range 340-250 nm is observed which is indicative of a psi (+)-type structure. At even higher concentrations (greater than or equal to 2.7 M), the Z-form is stable without condensation, and there is no change in the inverted CD spectrum. All structural transitions are reversible except that it is not possible to redissolve the highly condensed psi (+)-form by further increasing the salt concentration to greater than or equal to 2.7 M. The very high cooperativity of these transitions enables the DNA polymer to adopt three distinctly different structures (B-, Z-, and psi-forms) within a narrow range of sodium acetate concentration (approximately 200 mM). The Raman spectra of the condensed form and the Z-form in very concentrated sodium acetate show that the psi (+)-type state forms without substantial changes of the secondary conformation of the DNA. This indicates that the left-handed Z-helix of (dG-dC)n X (dG-dC)n can form psi-type aggregates with an ordered superstructure similar to those observed for natural right-handed DNA helices.

Acetates↗
PubMed1983

Attogram detection limit for aqueous dye samples by laser-induced fluorescence.

A modified flow cytometer has been used to detect attogram quantities of aqueous rhodamine 6G by laser-induced fluorescence analysis. A detection limit of 28 attograms (35,000 molecules) was obtained, nearly two orders of magnitude better than earlier measurements. The detection limit in concentration units was 1.4 x 10(-13) mole per liter. During the 1-second measurement period, the total volume sampled was 0.42 microliter. On average, only half a rhodamine 6G molecule was present in the 6-picoliter probed volume.

Flow Cytometry↗