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Biomedical subjects

J E Rose

Publications and source records attributed to J E Rose.

18 recordsLinked to original sources
PubMed1992

Concurrent agonist-antagonist administration for the analysis and treatment of drug dependence.

Two key strategies for the treatment of drug dependence involve the use of agonists to substitute for the abused drug and the use of antagonists to block the reinforcing actions maintaining drug self-administration. A different strategy for the treatment of drug dependence is outlined, comprising the concurrent administration of an agonist and an antagonist. Concurrent administration of an agonist with an antagonist, in the proper ratio, should produce maximal occupancy of receptors and attenuation of the reinforcing actions of the abused drug. The addict would be relatively "insulated" from the reinforcing effects of the abused drug; at the same time the balance of agonist and antagonist effects is predicted to prevent withdrawal symptoms or intoxication resulting from an under- or over-stimulation of drug receptors. Advantages over the use of agonists alone and antagonists alone, and over mixed agonist-antagonist molecules, are discussed. Application of concurrent agonist-antagonist administration to the analysis of mechanisms underlying nondrug reinforcement and to the treatment of disorders involving receptor disregulation is also described.

Animals↗
PubMed1992

Persistence of chronic nicotine-induced cognitive facilitation.

Nicotine has been found in a variety of species and behavioral paradigms to improve memory performance. The beneficial effect of nicotine has been seen after both acute and chronic administration. Interestingly, improved performance has been seen 24 h after acute injection and for at least 2 weeks after chronic administration. However, it is not clear from previous studies whether the persistence of the improved performance represents a true carryover of the drug effect or is due to the behavioral experience while under nicotine's effect. The current study was conducted to determine whether the facilitating effect of nicotine on learning and memory performance could be seen after withdrawal even if there was no behavioral training during the period of chronic nicotine administration. Rats were administered nicotine chronically for 3 weeks but were not tested during that time. Starting 1 week after withdrawal they were trained on a working memory paradigm in an eight-arm radial maze. The nicotine-treated rats started out at control-like levels of performance, but showed significantly faster learning as detected by three different measures of choice accuracy. By the final phase of testing the control subjects had caught up with the nicotine-treated rats. After the acquisition phase, acute challenges with the nicotinic and muscarinic antagonists, mecamylamine and scopolamine, did not elicit any differential effects in the nicotine-treated and control groups. The current study demonstrated that nicotine-induced cognitive facilitation persists for at least 4 weeks after withdrawal and does not depend upon behavioral test experience under the influence of the drug. The mechanism for this persisting effect is not currently understood.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Interactive effects of D1 and D2 agonists with scopolamine on radial-arm maze performance.

Pharmacological blockade of muscarinic cholinergic (ACh) receptors has been found to impair choice accuracy in a variety of tasks including the radial-arm maze. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the dopaminergic (DA) antagonist haloperidol as well as the selective D1 antagonist SCH 23390. In the current study, interactions were studied between scopolamine and selective agonists of D1 (SCH 38393) and D2 (quinpirole) receptors. Surprisingly, the D1 agonist SKF 38393 was found to significantly alleviate the scopolamine-induced choice accuracy deficit. In contrast, the D2 agonist quinpirole was not found to significantly alter the effects of scopolamine on choice accuracy but did have supra-additive effects of increasing choice latency. Both the D1 agonist SKF 38393 and the D1 antagonist SCH 23390 have been found to reverse the choice accuracy deficit caused by scopolamine and the deficit resulting from lesions of the medial projection from the basal forebrain to the cortex. Possible mechanisms for these effects are discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1979

Metabolic inhibition of plaque-forming cells: comparison of human rheumatoid-factor-producing cells with mouse anti-sheep erythrocyte-producing cells.

While rheumatoid-factor-producing haemolytic plaque-forming cells (RF--PFC) of the human peripheral blood were easily inhibited by cycloheximide, mouse spleen cells immune to sheep red cells (anti-SRC PFC) were inhibited only after prolonged preincubation in the drug. The RF--PFC were easily inhibited by propranolol, while the anti-SRC PFC were not at all inhibited. Vinblastine inhibited both systems equally. These differences are taken to suggest that the RF--PFC have very little preformed antibody in them and therefore depend upon active protein synthesis for their demonstration. In contrast, anti-SRC PFC, which may be predominantly mature plasma cells, generally need no new protein synthesis for their demonstration because of increased quantities of preformed antibody. A possible mechanism is that RF--PFC may represent primarily RF-specific B cells, the RF of which is released by surface immunoglobulin shedding and therefore susceptible to membrane stabilising agents such as propranolol.

Animals↗
PubMed1979

Alexia without agraphia in a musician after transcallosal removal of a left intraventricular meningioma.

After a meningioma situated in the trigone of the left lateral ventricle was excised by the transcallosal approach of Kempe and Blaylock, a right-handed musician with a right hemianopsia developed alexia without agraphia. In contrast to previously reported cases of this syndrome arising from other etiologies, he was unable to read single letters or numbers. Neuropsychological studies at 42 and 126 days after operation also disclosed an inability to associate auditory or tactile stimuli with visually perceived material, whereas speech and verbal comprehension were intact. Although the alexia extended to musical notes, he could interpret other musical symbols (e.g., treble clef). Appreciation of rhythm and expressive musical ability were relatively preserved, although judgment of other musical features (including discrimination of pitch, duration, and loudness) was compromised. The findings suggest that alexia may occur as a consequence of the transcallosal procedure when a right hemianopsia is present. However, other linguistic abilities may be better preserved by the transcallosal approach to the ventricle than by a transcortical operation.

Agraphia↗
PubMed1979

Radionuclide cerebral angiography and the timing of aneurysm surgery.

Forty-five patients with subarachnoid hemorrhage due to verified intracranial aneurysms were studied prospectively to determine whether delaying operations in those patients with abnormal cerebral perfusion, assessed by radionuclide dynamic scanning, would lower case management mortality. Twenty-nine patients had intracranial operations when their radionuclide dynamic scans demonstrated normal perfusion. The one death in this group occurred in a patient who suffered a massive hemorrhage during operation as the bone flap was elevated. There were no instances of delayed spasm after operation. Of the 16 remaining patients who were treated without operation, 5 died. Only 1 of these deaths resulted from recurrent hemorrhage. This patient had normal cerebral perfusion but was not operated upon because of severe associated medical problems. Cerebral infarction occurred in 10 of the 16 unoperated patients, all of whom had persistently decreased cerebral perfusion. Four of these patients died of their infarctions or related causes. Although a trend related vessel caliber as seen on arteriograms and perfusion delay seen on dynamic scanning, individual exceptions were numerous. This study shows that radionuclide scanning, a safe procedure, is useful for identifying two types of patients: those with normal perfusion prone to rebleeding in whom an early operation is safe and those in whom perfusion is decreased. The latter group is prone to cerebral infarction, but rebleeding from the aneurysm is unlikely. Operation should be delayed in these patients until cerebral perfusion returns to normal or for several weeks if cerebral perfusion remains diminished.

Adult↗
PubMed1979

Long-term neuropsychological outcome of closed head injury.

Long-term recovery from severe closed head injury was investigated in predominantly young adults whose Glasgow Coma score was 8 or less at the time of admission. Of the 27 patients studied (median follow-up interval of 1 year), 10 attained a good recovery, 12 were moderately disabled, and five were severely disabled. In contrast to previous studies suggesting that intellectual ability after severe closed head injury eventually recovers to a normal level, our findings showed that residual intellectual level, memory storage and retrieval, linguistic deficit, and personal social adjustment corresponded to overall outcome. All severely disabled patients and several moderately disabled patients exhibited unequivocal cognitive and emotional sequelae after long follow-up intervals. Analysis of persistent neuropsychological deficit in relation to neurological indices of acute injury severity demonstrated the prognostic significance of oculovestibular deficit.

Adolescent↗
PubMed1979

Complement activity and conglutinin activity in stored bovine sera.

Complement activity and conglutinin activity were measured in bovine sera stored under four conditions: phenolized (3 C), lyophilized (3 C), frozen (-23 C), and frozen (-57 C). The complement activity was lost after 12 weeks in phenol (3 C). The other three conditions, ranked in order of increasing effectiveness, are lyophilized (3 C) and frozen (-23 and -57 C). Conglutinin activity was lost after 23 weeks in phenol (3 C). The other three conditions, ranked in order of increasing effectiveness, are frozen (-23 C), lyophilized (3 C) and frozen (-57 C). Thus, the most effective condition to preserve complement and conglutinin simultaneously is freezing at -57 C.

Animals↗
PubMed1978

Temperature stress and immunity in mice: effects of environmental temperature on the antibody response to human immunoglobulin of mice, differing in age and strain.

Physiological responses at different ambient temperatures and temperature-dependent changes in immune responsiveness are polymorphic. At 4 degrees C, the antigen elimination from the bodies of SJL and C57Bl/6 mice is accelerated. In SJL, but not in C57Bl/mice, the half-life of antigen elimination decreased between the ages of 3 and 11 weeks. Parental mice and their F1 hybrids showed a fall in rectal temperature, which was greatest in young animals. Hypothermia was greater in C57Bl/6 than in SJL and F1 hybrids; in 3 week old C57Bl/6 it resulted in high mortality. The response to aggregated human immunoglobulin (HGG) was evaluated by (a) the number of animals with detectable antibody, (b) the minimal dose of antigen eliciting detectable antibody, and (c) the mean titre of haemagglutinating antibody. SJL mice were more responsive than C57Bl/6 mice. Low antibody formation in the secondary response was dominant, i.e. the amount of antibody produced by (SJL X C57Bl/6)F1 mice was the same as that produced by the parental C57Bl/6 strain. In a primary response, the quantity of antibody varied with the age of the immunized animal; 18 week old mice responded to lower minimal doses of antigen and produced more haemagglutinating antibody than 3 week old animals. After a second injection with HGG, SJL but not C57Bl/6 mice produced more antibody when kept at 14 degrees C rather than at 22 degrees C or 30 degrees C, and produced the lowest antibody titres when kept at 4 degrees C. The relation between ambient temperature and the response of the SJL mice was dominant over that of the C57Bl/6strain. Primary differed from secondary responsiveness in that neither strain produced significantly lower titres when ambient temperature fell to 4 degrees C; only 18 week old SJL mice responded with a marginal decrease in peak antibody production. The described polymorphism may affect both the individual capacity to cope with low temperatures and the evolutionary adaptation of a species to climatic extremes.

Age Factors↗
PubMed1978

Serum levels of conglutinin, complement, and immunoconglutinin in cattle infected with Anaplasma marginale.

Sera from 10 splenectomized yearling cattle given massive doses of Anaplasma marginale (peracute cases) were assayed for conglutinin and complement. Sera from 5 nonsplenectomized yearling cattle given smaller doses (acute cases) were assayed for conglutinin, immunoconglutinin, and complement. In the peracute cases, conglutinating activity disappeared within 6 days after the cattle inoculated. In the acute cases, conglutining began to disappear at 3 weeks after inoculation and had disappeared at peak parasitemia at 4 weeks. Conglutinin returned by 7 weeks after inoculation. In the same acute cases, immunoconglutinain appeared at 6 weeks after inoculation and then slowly disappeared. The complement levels in the peracute and acute cases did not change appreciably.

Agglutination Tests↗
PubMed1977

Growth in culture of the peripheral axons of the spiral neurons in response to displacement of the receptors.

Observations were made on the growth of the peripheral axons of the spiral neurons in injured explants of the cochlea of the mouse. Opening of the cochlear duct during explantation usually results in a displacement of the hair cells into the outgrowth zone if the basilar membrane of the excised organ of Corti faces the substrate. Spiral neurons respond with vigorous growth to the stress created by the displacement of their receptors. Two different growth reactions occur in succession: 1) growth by elongation of the synaptically engaged fibre 2) free growth. The response of the neuron to an incipient displacement of the hair cells is an elongation of the fibre while its contacts with the receptors are, at least partly, preserved. Most or all fibres that are connected with the displaced cells elongate. The growth is well organized, limited to the region of the displaced hair cells, and restricted in length by the position of the receptors. It is inferred that tension on the synaptically engaged fibre may be a stimulus for its growth and that the growth ceases when the tension is relieved. Continuous stress eventually leads to a rupture of the fibre. The break usually occurs near or at the terminals, leaving the terminals attached to the hair cells. The proximal end of the fibre--now free--starts to grow. The growth is independent of the receptors, unrestricted in length, uncontrolled in amount, and continues for at least three weeks after explantation. The path of the fibre is tortuous, and collaterals are often emitted. Free growth proceeds at a markedly faster rate than growth by elongation. Maintenance of the synapse and growth of the fibre seem to be mutually dependent events. A peripheral axon of the spiral neuron can sustain in culture a normal innervation pattern, without any obvious signs of abnormal growth, if its connections with the hair cells are undisturbed; it elongates in an organized manner, if these connections come under stress; it responds with an uninhibited growth if the connections are broken.

Animals↗
PubMed1976

Effect of cold exposure on the metabolism of immunoglobulins in rabbits.

The effect of low environmental temperature on the metabolism of IgG and IgM was examined in unimmunized rabbits. The half-lives of both IgG and IgM were less in animals kept at 4 degrees C for 6 weeks than in animals kept at 22 degrees C. Serum concentration of IgM and GG were unaltered by cold exposure but intravascular pool sizes tended to increase as a consequence of an expanded serum volume. Fractional turnover rates of both IgM and IgG were greater in cold-exposed animals. At both 4 degrees C and 22 degrees C, the fractional catabolic rate of IgM was independent of its serum concentration whereas that of IgG was correlated directly with its serum concentration. Absolute turnover of both IgM and IgG was accelerated by cold exposure. It is suggested that increased synthesis of immunoglobulin could account for the higher levels of antibody reportedly found in cold-exposed rabbits.

Animals↗
PubMed1976

Effect of vagotomy on anaphylaxis in the rat.

Vagatomy or atropinization protects rats from lethal anaphylaxis and histamine shock. These procedures do not significantly affect production of anaphylactic antibodies or release of histamine following induction of anaphylaxis. The response of the intestinal microvasculature during anaphylaxis is observed to consist of an early brief increase permeability followed by prolonged and irreversible damage. Cholinergic blockade abolishes the latter and markedly reduces deposition of colloidal carbon and immune complexes in the vessel. The possible relevance of these observations to development of chronic immunological vascular disease is discussed.

Anaphylaxis↗
PubMed1975

Organotypic development of the organ of Corti in culture.

The preservation and development of the innervation pattern in the organ of Corti have been studied in culture up to 27 days in vitro. The explants were obtained from the newborn mouse. Segments of the cochlear duct dissected together with the appropriate sectors of the spiral ganglion may retain their structural organization for about two weeks. Maturation of some nonneuronal elements which occurs during that time is followed by a subsequent regression of the organ. Only a fraction of the explanted neurons survive. However, the surviving neurons, if connected with the hair cell region, maintain a complex peripheral innervation pattern that contains all the major fibre components which characterize the normal pattern in a young mouse. The peripheral innervation pattern in culture seems largely composed of preserved fibres, that is, of fibres which at the time of explantation have already ramified within the organ of Corti. Nonetheless, there is evidence for growth or maturation, in culture, of at least some peripheral processes of the spiral neurons. Thus, only in older cultures is the innervation of the apical tip established. Likewise, it is only in older explants that the inner spiral bundle becomes prominent. Spiral neurons survive in culture in several modes. Most frequently, the central process is altogether absent and the neuron is effectively a unipolar cell which maintains only the peripheral process. A distinct minority of neurons is bipolar possessing both the peripheral process and a central axon which grows freely, though no central target is present. A neuron may survive also as a unipolar or, rarely, as a bipolar cell with no processes entering the organ of Corti. The observations imply that (1) most or all major fibre systems in the organ of Corti carry components of spiral neuron origin; (2) a small population of spiral neurons innervating a short segment of the organ contributes importantly not only to the radial but also to the spiral innervation of the segment.

Animals↗
PubMedDate not supplied

Drugs affecting the release of rheumatoid factor in a plaque-forming cell assay.

Addition of propranolol to the agarose phase of a plaque-forming cell (PFC) assay for rheumatoid factor (RF) caused reduction in the number of plaques seen. This reduction in rheumatoid factor plaque-forming cell (RF PFC) did not depend upon an effect at the beta-adrenergic receptor, since d- and 1-propranolol reduced equally well. Furthermore, in a series of polycyclic compounds with varying beta-receptor blocking capabilities there was no agreement between plaque reduction and blocking. When propranolol was tested in the agarose in an anti-sheep erythrocyte (SRC) plaque assay (anti-SRC PFC), it had no inhibitory effect, but it was capable of inhibiting the generation of new anti-SRC PFC in an in vitro culture. Propranolol is thought to exert these effects through its membrane stabilizing (anesthetic) properties.

Adrenergic beta-Antagonists↗