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Biomedical subjects

G A Jacobs

Publications and source records attributed to G A Jacobs.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and antiviral activity of 1-cyclobutyl-5-(2-bromovinyl)uracil nucleoside analogues and related compounds.

A series of racemic (1 alpha (E), 2 beta, 3 alpha)-1-[2,3-bis(hydroxymethyl)cyclobutyl]-5-(2-halovinyl)uracils was synthesized and evaluated in cell culture. The bromovinyl, iodovinyl, and chlorovinyl analogues, 13, 15, and 16, respectively, are all potent inhibitors of varicella zoster virus (VZV), but are less inhibitory to the replication of human cytomegalovirus (HCMV) and herpes simplex viruses 1 and 2 (HSV-1, HSV-2). The excellent anti-VZV activities of 13, 15, and 16 coupled with their virtual inability to inhibit WI-38 cell growth indicate high in vitro therapeutic indices. VZV thymidine kinase readily converts these compounds to their respective monophosphates but not to their corresponding diphosphates. Compound 13a, the (1'R) enantiomer of the bromovinyl analogue 13, was also synthesized, and its potency is comparable to that of the racemate. A lower homologue 14, (1 alpha (E),2 beta, 3 alpha)-1-[2-hydroxy-3-(hydroxymethyl)cyclobutyl]-5- (2-bromovinyl)uracil, was found to be inactive against VZV, HCMV, HSV-1, and HSV-2.

Antiviral Agents↗
PubMed1991

Anatomical relationships between sensory afferent arborizations in the cricket cercal system.

The anatomical relationships between sensory afferents within a topographic map in the cricket cercal sensory system were studied using a computer-based reconstruction system developed in our laboratory. Individual identified mechanosensory afferents were characterized physiologically, stained with cobalt, silver intensified, and reconstructed in three dimensions. All reconstructions were scaled to a common standard. The results indicate that there is very little variability in the position or extent of the terminal arborization of identified mechanosensory afferents. The topographic map was divided relatively equally into four regions representing each of the four classes of afferents studied. These regions were discrete but not completely segregated. Approximately 30% of the topographic map contained regions of overlap between two or more classes or afferents.

Abdomen↗
PubMed1991

Anatomy and physiology of identified wind-sensitive local interneurons in the cricket cercal sensory system.

1. A group of wind sensitive local interneurons (9DL Interneurons) in the terminal abdominal ganglion of the cricket Acheta domesticus were identified and studied using intracellular staining and recording techniques. 2. The 9DL interneurons had apparent resting potentials ranging from -38 mV to -45 mV. At this membrane potential, these cells produced graded responses to wind stimuli; action potentials were never observed at these resting potentials. However, when the 9DL interneurons were hyperpolarized to a membrane potential of approximately -60 mV, a single action potential at the leading edge of the wind stimulus response was sometimes observed. 3. The wind stimulus threshold of the 9DL interneurons to the types of stimuli used in these studies was approximately 0.01 cm/s. Above this threshold, the excitatory responses increased logarithmically with increasing peak wind velocity up to approximately 0.5 cm/s. 4. The 9DL interneurons were directionally sensitive; their response amplitudes varied with wind stimulus orientation. 9DL1 cells responded maximally when stimulated with wind directed at the front of the animal. The apparent peak in directional sensitivity of the 9DL2 interneurons varied between the side and the rear of the animal, depending upon the site of electrode penetration within the cell's dendritic arbor. 5. The locations of dendritic branches of the 9DL interneurons within the afferent map of wind direction were used to predict the excitatory receptive field of these interneurons.

Action Potentials↗
PubMed1991

Representation of sensory information in the cricket cercal sensory system. I. Response properties of the primary interneurons.

1. Six different types of primary wind-sensitive interneurons in the cricket cercal sensory system were tested for their sensitivity to the orientation and peak velocity of unidirectional airflow stimuli. 2. The cells could be grouped into two distinct classes on the basis of their thresholds and static sensitivities to airflow velocity. 3. Four interneurons (the right and left 10-2 cells and the right and left 10-3 cells) made up one of the two distinct velocity sensitivity classes. The mean firing frequencies of these interneurons were proportional to the logarithm of peak stimulus velocity over the range from 0.02 to 2.0 cm/s. 4. The other two interneurons studied (left and right 9-3) had a higher air-current velocity threshold, near the saturation level of the 10-2 and 10-3 interneurons. The slope of the velocity sensitivity curve for the 9-3 interneurons was slightly greater than that for the 10-2 and 10-3 interneurons, extending the sensitivity range of the system as a whole to at least 100 cm/s. 5. All of the interneurons had broad, symmetrical, single-lobed directional sensitivity tuning curves that could be accurately represented as truncated sine waves with 360 degree period. 6. The four low-threshold interneurons (i.e., left and right 10-2 and 10-3) had peak directional sensitivities that were evenly spaced around the horizontal plane, and their overlapping tuning curves covered all possible air-current stimulus orientations. The variance in the cells' responses to identical repeated stimuli varied between approximately 10% at the optimal stimulus orientations and approximately 30% at the zero-crossing orientations. 7. The two higher threshold interneurons (left and right 9-3) had broader directional sensitivity curves and wider spacing, resulting in reduced overlap with respect to the low-threshold class.

Animals↗
PubMed1990

Lessons from the aftermath of Flight 232. Practical considerations for the mental health profession's response to air disasters.

The fiery crash of a DC-10 at Sioux City, Iowa, on July 19, 1989, caused a crisis of major proportions, with attendant mental health needs. Various articles have described the need for psychological response teams in such crises. The present article provides practical guidelines for the preparation of a mental health disaster plan and for the coordination of a mental health team responding to a major air disaster. Such disasters can occur in any part of the country at any time. It is hoped that the suggestions in the present article will help teams that respond to future air disasters provide more rapid, effective, and efficient delivery of services to the survivors and their families, and the families of those who are killed.

Accidents, Aviation↗
PubMed1990

Postsynaptic changes at a sensory-to-motoneuron synapse contribute to the developmental loss of a reflex behavior during insect metamorphosis.

The larval-pupal transformation of the tobacco hornworm, Manduca sexta, involves the loss of many larval-specific behaviors, including a simple withdrawal reflex of the abdominal prolegs. This reflex is mediated by monosynaptic excitatory connections between afferents that innervate mechanosensory hairs on the proleg [the planta hairs (PHs)] and motoneurons that innervate proleg retractor muscles. In response to hormonal cues during the final days of larval life, the dendritic arbors of proleg retractor motoneurons regress extensively. Intracellular recordings indicate that the synaptic depolarization evoked in proleg motoneurons by electrical stimulation of PH afferents decreases by 78% during the larval-pupal transformation, over the same time course that the motoneuron dendrites regress. During the same period the number of PH afferents and the extent of their central projections may decrease slightly. To test the relative contributions of developmental changes in the presynaptic afferents and postsynaptic motoneurons to the weakening of the reflex pathway, we generated heterochronic mosaic pupae that retained one larval proleg. The PH afferents on the retained proleg retained their larval characteristics while their postsynaptic targets, the proleg motoneurons, appeared to regress normally. In the mosaic hemisegments, electrical stimulation of PH afferents evoked only a small synaptic depolarization of the proleg motoneurons, similar in amplitude to that recorded in normally developing pupae; thus, the developmental status of the afferents was irrelevant to the loss of the reflex. These findings suggest that postsynaptic changes, e.g., structural regression of motoneuron dendrites, may cause the weakening of the reflex pathway. This is the first demonstrated correlation between the hormonally mediated regression of motoneuron dendrites and the loss of a specific behavior during metamorphosis.

Animals↗
PubMed1989

An objective method for the evaluation of eye irritation in vivo.

It is generally agreed that intra- and interlaboratory variations in the evaluation of eye irritants are mainly due to the subjective judgement of eye lesions. The scoring of the palpebral conjunctivae is a typical example. To eliminate these difficulties in assessing eye irritants the relationship between corneal swelling, which can be determined using an objective technique, and the reading of other symptoms was investigated. The in vivo eye irritation assay was carried out on 34 substances according to the protocol laid down in Annex V, part B of Directive 79/831/EEC of the European Community on the classification, labelling and packaging of dangerous substances. Results were obtained for erythema, oedema, corneal opacity and corneal swelling. Erythema, oedema and opacity were evaluated according to the interpretation rules laid down in Annex VI, part IID of the EEC Directive 83/467/EEC. Corneal swelling was determined by the ultrasonic pachometer technique. Good correlations were found between the mean percentage corneal swelling after 24, 48 and 72 hr and the mean corneal opacity (r = 0.94) and erythema scores (r = 0.93) after the same observation times. The corneal swelling scores measured after 24 hr using the ultrasonic pachometer are comparable with those reported in the literature, which were obtained by optical pachometry. The good correlation with the other effects scored and the good repeatability of the results opens the possibility of introducing an objective and sensitive method into the ocular irritation assay and so reducing intra- and interlaboratory variations.

Animals↗
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↗