Parasites and the germ theory of disease.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
J Farley
Publications and source records attributed to J Farley.
Clinical surveillance of gynecologic cancer patients.
A survey of gynecologic oncologists was used to determine the optimum follow-up plan for asymptomatic, disease-free patients previously treated for a gynecologic malignancy. Ninety-four (91%) of 103 questionnaires were completed and returned. The majority of respondents recommended a clinic visit for these patients every 3 months for the first year after the completion of therapy, every 3 or 4 months for the second year, every 6 months for the following 3 years, and then annually after this initial 5-year period. Breast, abdominal, lymph node, and pelvic examinations, as well as a pap smear and stool guaiac, were done at each of these clinic visits. A yearly chest X ray was performed by the majority of the survey respondents for the first 3 years following initial treatment. Determinations of serum CA-125 and ovarian germ cell tumor markers were done at each follow-up appointment during the first 5 years after therapy if they were previously elevated. The patients' smoking habits were discussed with them by the majority of respondents. Mammograms were performed periodically before age 50 and then yearly after age 50 by most respondents. Serum cholesterol determinations were accomplished every 5 years or more frequently if indicated. Calcium supplementation was recommended for postmenopausal patients. The majority of respondents did not recommend routine vitamin supplementation or surveillance sigmoidoscopy.
Ambulatory Care↗
Adverse reactions to the preschool (fifth) dose of adsorbed diphtheria-pertussis-tetanus vaccine in Canadian children.
OBJECTIVE: To quantify accurately the rate of adverse reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine and to test the hypothesis that large local reactions are attributable to the diphtheria toxoid. DESIGN: Double-blind randomized controlled trial. SETTING: Suburban community public health unit. PARTICIPANTS: Healthy children 4 to 5 years of age with a history of having received four doses of adsorbed DPT vaccine. INTERVENTIONS: Subjects were given either the standard DPT vaccine (with 25 Lf units of diphtheria toxoid) or a modified DPT vaccine (with 10 Lf units of diphtheria toxoid). They were assessed 24 hours later by a nurse. Serum samples obtained before vaccination were tested for diphtheria and tetanus antitoxin levels by means of neutralization assay and enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of large local reactions (an area of redness or swelling or both of 5 cm or greater) 24 hours after vaccination in the two groups. Relation between serum antitoxin levels before vaccination and the rate of large local reactions in each group. RESULTS: Of the 250 subjects enrolled 124 received the standard vaccine and 126 the modified one. Large local reactions occurred in 71% of the subjects receiving the standard vaccine and 52% of those receiving the modified one (p less than 0.01). In the former group large erythematous reactions occurred significantly more often in those with an elevated prevaccination diphtheria antitoxin level than in those without an elevated level; no relation was found between such reactions and the prevaccination tetanus antitoxin level. Reduced arm movement was evident in 45% of the children in the two groups. Few had systemic adverse reactions. CONCLUSIONS: Large local reactions occur frequently after the preschool administration of the DPT vaccine. These reactions are uncomfortable but not serious. They result in part from the large amount of diphtheria toxoid in the standard DPT vaccine.
Child, Preschool↗
Protein kinase C inhibitors prevent induction and continued expression of cell memory in Hermissenda type B photoreceptors.
Injections of cAMP-dependent, Ca2+/calmodulin-dependent, or Ca2+/phospholipid-dependent protein kinases into Hermissenda crassicornis type B photoreceptors are sufficient to induce many of the changes in B-cell excitability produced by associative conditioning. We report that inhibitors of Ca2+/phospholipid-dependent protein kinases, but not inhibitors of cyclic nucleotide- or Ca2+/calmodulin-dependent protein kinases, prevent the induction as well as continued expression of learning-produced changes in type-B-cell excitability: reductions of voltage-dependent and Ca2(+)-activated K+ currents. Our results represent a direct demonstration of long-term (days) experientially induced modulation of ion-channel activity that is dependent upon persistent kinase activity.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Associative learning changes intrinsic to Hermissenda type A photoreceptors.
The eyes of the nudibranch mollusc Hermissenda have previously been shown to contain 2 classes of photoreceptors. Type B photoreceptors exhibit increased light responses and membrane excitability after repeated pairings of light and rotation and play an important role in the mediation of associatively produced reductions in phototactic behavior. Type A photoreceptors have also been shown to change with associative training. In previous research, Type A photoreceptors from trained animals were found to have reduced light responses. Because these recordings were obtained from synaptically intact cells, it was not possible to determine whether the effects of associative training reflected changes in synaptic input to Type A photoreceptors or intrinsic changes in somatic conductances. In the present study, intracellular recordings from synaptically isolated Type A photoreceptors were obtained on retention days after training, and pairing-specific decreases in light-induced generator potentials and decreases in resting input resistance were observed. Current- and voltage-clamp analysis of Type A photoreceptors from untrained animals revealed that an important determinant of the steady-state light response was a calcium-activated K+ current (IK-Ca). Thus, Type A photoreceptors also appear to be a primary site for associative information storage in Hermissenda. It is suggested that enhancement of IK-Ca by associative training may contribute to the diminished light response of Type A photoreceptors.
Accommodation, Ocular↗
Chemosensory conditioning of Hermissenda crassicornis.
Bite-strike responses of Hermissenda crassicornis, elicited by chemosensory stimulation of the lips, were found to be modified when food extracts were paired with rotation-produced stimulation of the statocysts. Animals that received repeated pairings of an extract of 1 food (conditioned stimulus, CS) with rotation exhibited suppressed bite-strike responses to that food for up to 48 hr after training. This suppression was usually specific to the trained food and was pairing-specific as well. Discriminative conditioning was also demonstrated. Animals trained with 1 CS paired with rotation and a second CS that was unpaired (CS-) showed suppressed bite-strike responses to the first CS. The results demonstrate that Hermissenda can learn to avoid foods that reliably signal an aversive event and may allow an analysis of higher order conditioning phenomena.
Animals↗
Serotonin modulation of Hermissenda type B photoreceptor light responses and ionic currents: implications for mechanisms underlying associative learning.
Type B photoreceptors in the eyes of the nudibranch mollusc Hermissenda have previously been shown to exhibit enhanced steady-state depolarizing light responses, increases in steady-state light-induced impulse frequency and a decrease in resting membrane conductance on days following exposure to repeated pairings of light and rotation. These training-produced changes in the electrophysiological properties of B cells have been attributed to reductions in a voltage-dependent K+ current (IA), a calcium-activated K+ current (IK-Ca), and enhancement of a voltage-dependent Ca2+ current (ICa). Current- and voltage-clamp analysis of the effects of serotonin (5-HT) upon B cells revealed that 5-HT mimicked many of the effects of associative training. 5-HT enhanced the steady-state light response and decreased resting membrane conductance of B cells. Voltage-clamp analysis revealed five distinct effects of 5-HT upon the voltage-, calcium-, and light-dependent ionic conductances of B photoreceptors. In the dark-adapted cell, 5-HT enhanced but then suppressed IA, IK-Ca, and enhanced ICa. The presentation of 5-HT in combination with light accelerated the reduction of K+ currents. 5-HT also transiently reduced the fast component of light-induced inward current (INa-light), and enhanced a slower component of light-induced inward current. In an accompanying paper, 5-HT is shown to be localized within the cerebropleural neuropil where terminals presynaptic to B photoreceptors are located. Disruption of serotonergic neurotransmission by a variety of drugs is also shown to reduce the pairing-specific differences in Type B photoreceptor cumulative depolarization and resting membrane conductance decreases that are produced by in vitro conditioning. Collectively, the results indicate that 5-HT plays an important role in mediating the conductance changes produced in Type B photoreceptors by associative training.
Animals↗
Neurochemical and immunocytochemical studies of serotonin in the Hermissenda central nervous system.
In the preceding paper we showed that serotonin mimics the effects of associative conditioning on Type B photoreceptors of Hermissenda. Here we show that serotonin is present in the Hermissenda central nervous system, and that it is released in a calcium-dependent manner. A large number of serotonergic cell bodies are present in the cerebropleural ganglia (CPG). Cell bodies in the CPG are located in three small, symmetrical clusters. One cluster (2-3 cells) located at the anterior end of the CPG contains a large cell that projects to the buccal ganglion. A second cluster (2-3 cells) is located posterior to the first and near the midline of the nervous system. A third cluster (1-2 cells) was located slightly more posteriorly than the second. Type B photoreceptors and the S/E optic ganglion cell project to a region of the CPG neuropil which is heavily innervated by serotonin immunoreactive fine processes. Since serotonin mimicked the effects of associative conditioning on Type B cells, and is present in an appropriate region of the CPG neuropil, serotonin may mediate some effects of associative conditioning on Type B cells. Results supporting this hypothesis are presented in an accompanying paper.
Animals↗
Serotonin involvement during in vitro conditioning of Hermissenda.
To determine if serotonin may be involved in associative conditioning-produced changes in the excitability and photoresponses of Type B photoreceptors, isolated nervous systems were exposed to an in vitro conditioning procedure in the presence or absence of drugs that alter normal serotonergic neurotransmission. Pairings of light and intracellular depolarization of a caudal hair cell (in vitro conditioning) produced a pairing-specific depolarization of Type B photoreceptors that was accompanied by an increase in resting input resistance. Treatment of nervous systems with pharmacological agents which disrupt 5-HT neurotransmission attenuated membrane potential and input resistance changes of Type B photoreceptors. These drugs included serotonin uptake inhibitors (imipramine, fluoxetine), a receptor antagonist (bufotenine), and a neurotoxin (5,7-dihydroxytryptamine; 5, 7-DHT). Yohimbine, an alpha 2-receptor antagonist, was without effect. These results, and those in the accompanying papers, suggest that serotonin modulates Type B photoreceptor excitability during associative conditioning.
5,7-Dihydroxytryptamine↗
Parasites and the germ theory of disease.
Particular options for framing disease are not equally available to would-be framers. The history of parasitology in the nineteenth and early twentieth centuries suggests ways in which models drawn from the study of parasitic organisms might have influenced debates over the etiology of infectious diseases and led to a unified theory if parasitology had not been segregated intellectually. Intellectual and institutional history thus determined that the study of parasites would offer little to the modern germ theory of disease by making its models unavailable to physicians and biologists seeking to understand particular ills.
Disease↗
Multiple types of voltage-dependent Ca2+-activated K+ channels of large conductance in rat brain synaptosomal membranes.
K+-selective ion channels from a mammalian brain synaptosomal membrane preparation were inserted into planar phospholipid bilayers on the tips of patch-clamp pipettes, and single-channel currents were measured. Multiple distinct classes of K+ channels were observed. We have characterized and described the properties of several types of voltage-dependent, Ca2+-activated K+ channels of large single-channel conductance (greater than 50 pS in symmetrical KCl solutions). One class of channels (Type I) has a 200-250-pS single-channel conductance. It is activated by internal calcium concentrations greater than 10(-7) M, and its probability of opening is increased by membrane depolarization. This channel is blocked by 1-3 mM internal concentrations of tetraethylammonium (TEA). These channels are similar to the BK channel described in a variety of tissues. A second novel group of voltage-dependent, Ca2+-activated K+ channels was also studied. These channels were more sensitive to internal calcium, but less sensitive to voltage than the large (Type I) channel. These channels were minimally affected by internal TEA concentrations of 10 mM, but were blocked by a 50 mM concentration. In this class of channels we found a wide range of relatively large unitary channel conductances (65-140 pS). Within this group we have characterized two types (75-80 pS and 120-125 pS) that also differ in gating kinetics. The various types of voltage-dependent, Ca2+-activated K+ channels described here were blocked by charybdotoxin added to the external side of the channel. The activity of these channels was increased by exposure to nanomolar concentrations of the catalytic subunit of cAMP-dependent protein kinase. These results indicate that voltage-dependent, charybdotoxin-sensitive Ca2+-activated K+ channels comprise a class of related, but distinguishable channel types. Although the Ca2+-activated (Type I and II) K+ channels can be distinguished by their single-channel properties, both could contribute to the voltage-dependent Ca2+-activated macroscopic K+ current (IC) that has been observed in several neuronal somata preparations, as well as in other cells. Some of the properties reported here may serve to distinguish which type contributes in each case. A third class of smaller (40-50 pS) channels was also studied. These channels were independent of calcium over the concentration range examined (10(-7)-10(-3) M), and were also independent of voltage over the range of pipette potentials of -60 to +60 mV. Type III channels were unaffected by internal TEA concentrations <50 mM. Our results also indicate that the study of K+ channels in lipid bilayers may allow the identification and characterization of novel K+ channels from brain regions otherwise inaccessible to conventional recording techniques.
Animals↗
Myths & facts about gastrointestinal bleeding.
Explore the source record for details and available documents.
Gastrointestinal Hemorrhage↗
Myths & facts about suctioning techniques.
Explore the source record for details and available documents.
Humans↗
Myths & facts about chest tubes.
Explore the source record for details and available documents.
Drainage↗
Demonstration of reduced mitogenic and osteoinductive activities in demineralized allogeneic bone matrix from vitamin D-deficient rats.
Osteoinduction is the formation of ectopic bone that follows implantation of demineralized allogeneic bone matrix (DABM) and is believed to be secondary to the release of associated inductive factors from bone matrix. To clarify the role of vitamin D in osteoinduction, we implanted DABM from vitamin D-deficient rats (-D rats) into normal rats (+D rats). Because mitogens and osteocalcin might be involved in osteoinduction, these were measured. Mitogenic activity in extracts from mineralized allogeneic bone matrix (ABM) and DABM from both +D and -D rats was determined with an assay that utilizes monolayer cultures of embryonic chick calvarial cells. Osteocalcin in serum and DABM was measured by radioimmunoassay. DABM from -D rats did not promote osteoinduction as effectively as DABM from +D rats. Resorption of implant matrix from -D rats was diminished compared with resorption of matrix from +D rats (P less than 0.01), and the decrease was attributed to a corresponding decrease in the number of osteoclasts in the implants (P less than 0.02). Bone formation (P less than 0.01) and total implant mineralization (P less than 0.001) were significantly reduced in implants from -D rats, and the reductions corresponded with a decline in the number of osteoblasts (P less than 0.05). Mitogenic activity in DABM from +D rats was only slightly decreased as compared with activity in ABM, but DABM from -D rats contained significantly less activity (P less than 0.001). No mitogenic activity was identified in implants of DABM from either +D or -D rats 3 wk after implantation. Serum osteocalcin was significantly higher in -D as compared with +D animals. In contrast, the concentrations of osteocalcin in DABM from the two groups of animals were not significantly different from each other. These findings indicate that the diminished osteoinductive activity of DABM from -D rats results from deficiency of one or more mitogenic factors that are essential for inducing the proliferation and differentiation of bone cells at the implant site and that osteocalcin does not play a role in this regard.
Animals↗
Motor correlates of phototaxis and associative learning in Hermissenda crassicornis.
Motor correlates of Hermissenda phototactic behavior and their modification by associative training were examined. Anatomical studies indicated the posterior three-fourths of the foot to be innervated by nerve P1 while the anterior portion was innervated by nerve P2. Bilateral lesions of either P1 or P2 pedal nerves in untrained animals reduced phototactic behavior. Extracellular recordings of pedal nerves from untrained animals revealed significant increases in total multi-unit activity (MUA) during a light presentation. Prominent components of nerve P2 activity were synchronous bursts apparent in peri-stimulus time (PST) histograms. Burst frequency was increased by light. Associative training resulted in significant decreases in light-evoked MUA frequency in P1 and light-evoked burst frequency in P2. Intracellular recordings were obtained from three classes of putative motoneurons with axons in P2. These were located using cobalt backfills and verified for each preparation by simultaneous extracellular recording from P2. The characteristic pattern of activity of these cells in the dark and its modulation by light was established.
Animals↗
Training and testing determinants of short-term associative suppression of phototaxic behavior in Hermissenda.
Hermissenda crassicornis shows both short- and long-term retention of conditioning following light-rotation pairings. Previous research has shown that prolonged training (50 trials per session, three consecutive daily sessions) produces a suppression of phototaxis lasting for days. This long-term retention reflects associative learning processes, with little or no contribution of nonassociative learning. In contrast, both associative learning and nonassociative behavioral modification contribute to short-term retention following a single session of five pairing trials. In this paper, we describe important associative and nonassociative determinants of short-term changes in phototaxis. In Experiment 1, animals received successive hourly tests for phototaxis in either a horizontal or a vertical orientation. Repeated testing resulted in decreased phototaxis which was especially pronounced for animals tested horizontally. Experiments 2-4 demonstrated that both repeated handling of animals and repeated periods of dark adaptation prior to each phototaxic test contributed to the development of phototaxic suppression with repeated testing. These nonassociative influences on phototaxis interacted with the gravitational orientation employed during behavioral testing, being most pronounced for testing in the horizontal orientation. An implication of these findings is that attempts to demonstrate short-term pairing-specific suppression will be most successful when nonassociative contributions are minimized (by testing animals vertically). Experiment 5 tested this prediction. We also tested the influence of training light intensity and the stimulus specificity of conditioned suppression. Animals received either five paired or five random presentations of light and rotation. Training light intensity was either moderate or bright. Following training, animals were tested for either suppression of phototaxis or suppression of negative geotaxis, using either a horizontal or a vertical testing orientation. Consistent with previous results, horizontally tested animals exhibited pronounced nonassociative suppression following training. The use of a bright training light also produced nonassociative suppression. However, when trained with a light of moderate intensity and tested vertically, Hermissenda showed associative suppression of phototaxis (significant paired--random difference) but not geotaxis (no paired--random difference). In a final experiment we observed that the longer the period of dark adaptation (prior to testing) the longer the phototaxic latency.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Contingency learning and causal detection in Hermissenda: I. Behavior.
The addition of extra light-alone or rotation-alone presentations to sequences of light-rotation pairings reduced the associative suppression of phototaxic behavior for the nudibranch Hermissenda. Training-induced changes in Type B photoreceptor light responses were found to parallel the training-induced behavioral changes in the intact animal. The decremental effects of the degraded contingency treatments upon neural and behavioral changes normally occasioned by light-rotation pairings reflected two processes. One factor was the increased stimulation frequency entailed by degraded contingency training. The second factor reflected the specifically unpaired character of the added light-alone or rotation-alone presentations, independent of frequency changes. The attenuation of phototaxic suppression was not because of a general habituation process or adaptation to the effects of either visual or vestibular stimulation. Instead, attenuation seemed to reflect a local interference effect of interspersed unpaired stimuli. The present experiments demonstrate a sensitivity to stimulus contingencies for Hermissenda similar to that of many vertebrates and indicate that contiguity and contingency relations are both encoded and stored in the Type B photoreceptors. The results indicate that similar neurophysiological mechanisms are involved.
Animals↗