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Biomedical subjects

G A Jacobs

Publications and source records attributed to G A Jacobs.

At least 37 records · Page 2Linked to original sources
PubMed1989

Evaluation of a non-invasive human and an in vitro cytotoxicity method as alternatives to the skin irritation test on rabbits.

5 substances were investigated for their primary irritant effect by means of different protocols. The cutaneous blood flow values (CBFV) were measured in humans: in a 1st series of experiments 12 h after application of the pure substances for 48 h and in a 2nd series of experiments 1, 24, 48 and 72 h after application of the 10% diluted substances (subclinical concentration) for 3 h. Rabbit skin erythema scores were obtained 1, 24, 48 and 72 h after application of the undiluted substances for 4 h. The uridine uptake inhibition assay on KB cells was included as a cytotoxicity test. Results obtained for both protocols on humans are compared with each other and with the test data obtained on rabbits, and with the cytotoxicity data. Application of the undiluted substances for 48 h on human skin or for only 3 h at a 10% dilution resulted in the same ranking between the substances. The CBFV in the human correlated very well (r = 0.99) with erythema scores obtained on rabbits. A poor correlation was observed between the in vitro and the in vivo results. From this study, it can be concluded that CBFV measurement is a valid method for the detection of erythema at subclinical concentrations.

Animal Testing Alternatives↗
PubMed1988

Personality and smokeless tobacco use.

Smokeless tobacco use and personality factors associated with smokeless tobacco use were examined in a broad, representative sample of 8th and 10th graders from central and south-central Florida (n = 1413). Current, occasional, or ex-users of smokeless tobacco accounted for 51% of the males and 9% of the females. Smokeless tobacco users, as compared to non-users, had significantly higher Trait Anger, and Angry Temperament and Angry Reaction subscale scores on the State-Trait Personality Inventory, suggesting a possible role in the initiation of smokeless tobacco use. There were no differences in Trait Anger, Anxiety, or Curiosity scores between the three user groups, suggesting that trait personality does not play a role in the maintenance of smokeless tobacco use.

Adult↗
PubMed1987

Segmental origins of the cricket giant interneuron system.

The segmental origins of the cricket giant interneuron system have been studied by staining these neurons with cobalt during the last half of embryonic development. The results demonstrate that the interneurons are derived from three distinct clusters of embryonic neurons that form a serially repeating pattern in each abdominal ganglion. Some of the neurons previously described in adults (Mendenhall and Murphey, '74; Murphey, '85) have been identified in embryos and are described here with respect to this pattern. These neurons include both giant interneurons and several non-giant mechanosensory interneurons that mediate several different sensory modalities. The anatomical organization of this system is compared to similar mechanosensory systems in other insects and crustacea.

Abdomen↗
PubMed1987

A reflex behavior mediated by monosynaptic connections between hair afferents and motoneurons in the larval tobacco hornworm, Manduca sexta.

In the tobacco hornworm caterpillar, tactile stimulation of sensory hairs located on the tip of a proleg (the planta) evokes ipsilateral or bilateral retraction of the prolegs in that segment. We have used electrophysiological and anatomical methods to investigate the excitatory neural pathways linking the planta hair afferents and the proleg retractor motoneurons (MNs). An important technical innovation was the development of an isolated proleg and desheathed ganglion preparation that permits rapid and reversible ionic manipulations and drug applications. Action potentials (spikes) in individual planta hair afferents produce time-locked excitatory postsynaptic potentials (EPSPs) in ipsilateral proleg MNs which appear to be chemically-mediated and monosynaptic: the EPSPs have a short and constant latency, they follow afferent spikes without failure, they are reversibly abolished in elevated Mg++ saline, and they persist in saline with elevated Mg++ and Ca++ levels. Planta hair afferents also excite ipsilateral MNs by polysynaptic pathways, and their excitation of contralateral proleg MNs is exclusively polysynaptic. Cobalt-staining of the proleg MNs and planta hair afferents shows that the afferents terminate in ventral neuropil, and the proleg MNs have an unusual ventral projection into this region. The ventral projection is on the ipsilateral side, which is consistent with the electrophysiological finding that time-locked EPSPs are found only from ipsilateral hairs. Two factors that contribute to the strong monosynaptic excitation of proleg MNs by ipsilateral planta hairs are the convergence of many hair afferents onto each MN, and the facilitation shown at each afferent-MN synapse. At least 6 afferents converge on each MN, and at short interspike intervals the afferent-evoked EPSPs are enhanced by as much as 400% by homosynaptic facilitation. The EPSP is abolished reversibly by the cholinergic antagonists curare and atropine, suggesting that the neurotransmitter at the synapse is acetylcholine (ACh). This is of particular interest because the ACh receptors of tobacco-feeding Manduca larvae are reported to be less nicotine-sensitive than those of other insects.

Acetylcholine↗
PubMed1987

Emotional and familial determinants of elevated blood pressure in black and white adolescent males.

The relationships between blood pressure and several personality and traditional risk factors were examined in a sample of black and white adolescent males who were enrolled in a health science course in Tampa, Florida. Although a number of personality and traditional risk factors significantly predicted elevated blood pressure for both groups of adolescent males, suppressed anger and weight were the major independent predictors. Among black and white males, those who generally harbored grudges and suppressed their anger had higher systolic blood pressure; diastolic blood pressure was higher only for the white males who frequently held in their angry feelings. Weight and excessive salt usage significantly predicted both elevated systolic and diastolic pressures for white males, while these variables significantly predicted systolic pressures for black males. Familial factors were found to be independent predictors of systolic and diastolic blood pressure only for the white adolescent males. A further examination of the relationship between the frequency that anger is suppressed shows that the shape of the curves relating anger-in scores to blood pressure appears to have a 'threshold'. These findings indicate that adolescent males who are at increased risk for elevated systolic and diastolic blood pressure can be identified by how often angry feelings are held-in and suppressed.

Adolescent↗
PubMed1986

In vitro susceptibility of the Bacteroides fragilis group in community hospitals.

The antimicrobial susceptibility of clinical isolates of the Bacteroides fragilis group was determined at six community hospitals (one large, greater than 600 beds; and five smaller, 96-325 beds). Imipenem was the most active beta-lactam with 100% of isolates being sensitive at 4 micrograms/ml. The percentage of isolates inhibited at 16 micrograms/ml (and 32 micrograms/ml) for the 7-alpha-methoxy antibiotics was: cefoxitin 66 (90); moxalactam 73 (85); cefotetan 68 (72); cefmetazole 40 (61). Metronidazole, chloramphenicol, and clindamycin were active against 100%, 100%, and 89% at breakpoints of 8 micrograms/ml, 8 micrograms/ml, and 4 micrograms/ml, respectively. The activity of several beta-lactams in our report differed slightly from that reported from university teaching hospitals. There were differences at many of the breakpoints for activity of some of the beta-lactam antibiotics for isolates from the large community hospital as compared with the combined isolates from the smaller community hospitals. Interestingly, the pattern was one of more resistance at the smaller community hospitals.

Anti-Bacterial Agents↗
PubMed1986

Integrative mechanisms controlling directional sensitivity of an identified sensory interneuron.

Several identified interneurons in the cricket cercal afferent system display directional sensitivity to wind stimuli: the spike frequency of these cells depends on the wind direction with respect to the animal's body. Factors determining the directional sensitivity of one of these identified interneurons (interneuron 10-3) were studied in detail. This cell has 3 dendritic branches that arborize in 3 distinct regions of the terminal abdominal ganglion. Using 2 independent methods, it was demonstrated that the dendrites have different receptive fields to wind stimuli. First, small patches of filiform hairs, whose afferents projected to individual dendrites, were isolated and selectively stimulated. In each case the response of the cell matched the receptive field of the afferents in the patch. Second, a laser beam directed through the stereo dissecting microscope was used to photoinactivate small portions of the cell in situ during intracellular recording. By isolating or ablating individual dendrites, the contributions of each of the 3 dendrites to the overall receptive field were assessed. Although the receptive field of the whole cell could be predicted by a summation of the receptive fields of all 3 dendrites, the precise directional sensitivity of the cell could not be predicted by a simple linear summation of the receptive fields of each dendrite. Two factors were found to account for this nonlinearity of summation. The first factor was polysynaptic inhibition from other interneurons within the terminal abdominal ganglion. Wind directions that activate inhibition in interneuron 10-3 were identified, and the specific classes of filiform afferents that activate the inhibitory pathway were determined. The net effect of the inhibition was to "sharpen" the directional sensitivity of 10-3 by selectively decreasing the cell's response to specific excitatory inputs. The second factor that contributed to directional sensitivity was the complex electroanatomy of the interneuron. The probable location of the spike-initiating zone (SIZ) was determined by using the laser photoinactivation technique. The relative efficacies of synaptic inputs onto the 3 different branches were then interpreted with respect to their different electrotonic distances from the SIZ. On the basis of the data obtained in this report, we present a qualitative model for the basis of directional sensitivity in this cell.

Animals↗
PubMed1985

Functional properties of individual neuronal branches isolated in situ by laser photoinactivation.

The functional properties of an isolated dendritic branch of an identified sensory interneuron in the cricket were studied. The branch responded to wind stimuli directed at the animal and displayed a distinct directional sensitivity to those stimuli. A technique was used that allows a neuron to be specifically lesioned in a semi-intact preparation during intracellular recording. Lesioning was achieved by dye-sensitized photoinactivation with a laser epi-illumination stereomicroscope.

Action Potentials↗
PubMed1985

Impact of dilution on the pharmacokinetic behavior of acetaminophen in rabbits after oral administration.

Seven rabbits received two different acetaminophen solutions by gavage in a randomized crossover fashion. In one administration the dose was given in a concentrated small volume of an ethanol-glycerol-water mixture (preparation I). In another administration an identical dose was given in a 10-fold water-diluted volume of the same mixture (preparation II). Three rabbits also received the same dose in a 10-fold original mixture volume (preparation III). The acetaminophen concentrations were measured by HPLC in plasma samples collected for 3.5 h after gavage. The lag times ranged from 2.5 to 23 min for preparation I and from 2.2 to 29 min for preparation II. The mean peak plasma concentrations (12.38 micrograms/mL for preparation I and 9.14 micrograms/mL for preparation II) and the mean time-to-peak concentrations (26.57 min for preparation I and 36.57 min for preparation II) were significantly different. The total area under the plasma concentration curve and the absorption and elimination half-lives did not, however, differ significantly. For the three rabbits receiving the acetaminophen doses in the 10-fold ethanol-glycerol-water mixture volumes (preparation III), the total area under the plasma concentration curve obviously was increased.

Acetaminophen↗
PubMed1985

Antiparasitic agents. 6. Synthesis and anthelmintic activities of novel isothiocyanatophenyl-1,2,4-oxadiazoles.

The syntheses and anthelmintic activities of 31 3- and 5-(isothiocyanatophenyl)-1,2,4-oxadiazoles are reported. In the primary anthelmintic screen, 3-(4-isothiocyanatophenyl)-1,2,4-oxadiazole (39) showed 100% nematocidal activity and 3-(2-furanyl)-5-(4-isothiocyanatophenyl)-1,2,4-oxadiazole (63), 3-(2-furanyl)-5-(2-chloro-4-isothiocyanatophenyl)-1,2,4-oxadiazole (64), and 3-(2-furanyl)-5-(4-chloro-3-isothiocyanatophenyl)-1,2,4-oxadiazole (66) showed 100% taeniacidal activity when administered orally to mice. The two most active members of this series, 39 and 63, were active against the gastrointestinal nematodes of sheep at 100 mg/kg. In addition, 39 was also found to be active against hookworms in dogs at a single, oral dose of 200 mg/kg.

Ancylostomiasis↗
PubMed1984

Relationships between neuronal structure and function.

The geometry and electrical properties of a neurone determine how synaptic inputs and endogenously generated currents are integrated and transformed into the signals it transmits to other cells. The dependence of neuronal integration upon dendritic geometry has been studied extensively over the last three decades, both by experimentalists and by theoreticians. We review some of the general principles that have emerged from this work, and summarize recent studies that serve to illustrate these principles. The discussion is organized around the analysis of neuronal structure at three different levels. At the 'macroscopic' level, we show how the dendritic branching structure of an identified interneurone in the cricket cercal afferent system determines the directional sensitivity within its receptive field. At the 'microscopic' level, we illustrate the dependence of synaptic efficacy upon dendritic length, and demonstrate a very surprising result: that the extension (or 'growth') of a dendrite out beyond the point of a synaptic contact can increase the efficacy of that synapse. At the 'ultrastructural' level, we show how the structural and electrical properties of dendritic spines might have profound effects upon synaptic integration.

Dendrites↗
PubMed1984

Neurospecificity in the cricket cercal system.

Studies of neurospecificity in the cricket cercal sensory system are reviewed and a decade of experimentation is examined in the light of recently obtained anatomical data. The nearly complete description of the anatomy indicates that the excitatory receptive fields of directionally-selective interneurones are a joint function of an orderly afferent projection and the dendritic structure of the first order interneurones. The detailed understanding of the anatomy is shown to be a powerful tool in the interpretation of previously published physiological experiments and the design of new ones. The mechanisms which shape the orderly afferent projection are then described and compared with the work on vertebrate sensory systems. It is concluded that both positional interactions of the type conceived by Sperry (1963) and competitive interactions of the type conceived by Hubel, Wiesel & LeVay (1977) are involved in producing the cercal afferent projection. Thus the two main components of the neurospecificity concept are shown to exist in the cricket nervous system. The limits of a purely anatomical approach to the study of neurospecificity are considered in light of the work on this cricket sensory system.

Afferent Pathways↗
PubMed1982

Antiparasitic agents. 5. Synthesis and anthelmintic activities of novel 2-heteroaromatic-substituted isothiocyanatobenzoxazoles and benzothiazoles.

The synthesis and antiparasitic properties of 22 isothiocyanato-2-pyridinylbenzoxazoles and benzothiazoles are described; the preparation and anthelmintic activities of 14 isothiocyanato-2-thienyl-, -furyl-, and -pyrrolylbenzoxazoles are outlined. In mice experimentally infected with Nematospiroides dubius (nematode) and Hymenolepis nana (tapeworm), three derivatives, i.e., 5-isothiocyanato-2-(2-furyl)benzoxazole (34), 5-isothiocyanato-2-(5-methyl-2-furyl)benzoxazole (35), and 5-isothiocyanato-2-(1-methyl-1H-2-pyrroly)benzoxazole (37), show 100% nematocidal activity and two, i.e., 5- and 6-isothiocyanato-2-(3-pyridinyl)benzoxazole (5) and 5- and 6-isothiocyanato-2-(3-pyridinyl)benzthiazole (21), show 10% taeniacidal activity at 0.2% in the diet. Two derivatives (5 and 21) show good nematocidal activity in sheep. Maximum activity requires 3-pyridinyl derivatives for both the benzoxazole and benzothiazole series.

Animals↗
PubMed1982

Personality and smoking behavior.

Investigated the relationship between selected personality measures and the initiation and maintenance of smoking behavior. The Eysenck Personality Questionnaire (EPQ), the State-Trait Personality Inventory (STPI) and a Smoking Behavior Questionnaire were administered to 955 students (603 females; 352 males). Smokers had significantly higher scores than Nonsmokers on the EPQ Extraversion, Neuroticism and Psychoticism scales, and lower scores on the Lie Scale. Female Smokers had higher STPI Trait Anxiety scores than Nonsmokers, whereas male Smokers had lower anxiety scores than Nonsmokers. Female Current Smokers had lower Neuroticism and Trait Anxiety scores than Occasional and Ex-Smokers, and Ex-Smokers of both sexes had higher scores on the STPI Trait Curiosity scale than Current and Occasional Smokers. It was concluded that the initiation and maintenance of smoking behavior are influenced by different personality factors.

Adult↗
PubMed1976

Ion binding and chromatin condensation.

1. The binding of 45Ca2+ to hen erythrocyte chromatin has been studied to help elucidate how cations induce a reversible condensation of this chromatin. 2. As the unbound Ca2+ of the medium rises from 0.5 to 4 mM, Ca2+ is bound to the chromatin with a stability constant of approx. 3.1 and a saturation value of 0.25 Ca2+ per DNA phosphate, or one-half the value for pure DNA. Condensation of the chromatin is half complete when this binding of calcium is roughly half complete. Hence the transition from the uncondensed to the condensed state occurs as repulsion between the free DNA phosphates of erythrocyte chromatin is neutralised by bound cations. Genetically active chromatin may be maintained in an uncondensed state in living cells by the presence of different negative groups that remain unneutralised at the unbound cation concentrations of the cell. 3. That only one-half of the calcium binding sites of DNA are masked in erythrocyte chromatin supports recent models of chromatin structure in which the DNA double helix is wound round a core of histones. 4. Competition for calcium binding sites in the chromatin by other cations was also studied.

Animals↗