PubMed Health⌕ Search

Biomedical subjects

B J Johnson

Publications and source records attributed to B J Johnson.

At least 73 records · Page 4Linked to original sources

Dihydrexidine, a full D1 dopamine receptor agonist, induces rotational asymmetry in hemiparkinsonian monkeys.

Dihydrexidine (trans-10,11-dihydroxy5,6,6a,7,8,12b hexanhyydrobenso- [alpha]phenanthridine) is a full dopamine D1 agonist. In rhesus macaque monkeys rendered hemiparkinsonian by unilateral intracarotid infusions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), dihydrexidine (0.15-0.9 mg/kg) elicited dose-dependent contralateral rotation. The effects of dihydrexidine were blocked by pretreatment with the D1 antagonist SCH 23390 (0.03 mg/kg), but not by the D2 antagonist raclopride (0.025 mg/kg). These results suggest a functional role for D1 receptors in stimulating motor behavior in a primate model of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Incomplete protection of hamsters vaccinated with unlipidated OspA from Borrelia burgdorferi infection is associated with low levels of antibody to an epitope defined by mAb LA-2.

Efforts to develop a recombinant vaccine for Lyme disease have focused on using the outer surface protein A (OspA) of Borrelia burgdorferi as an immunogen. We evaluated the effectiveness of an unlipidated recombinant OspA as a vaccine in hamsters. This molecule is soluble and can be produced in high yield in Escherichia coli, characteristics that permit simple and relatively low cost production. Vaccination with unlipidated OspA protected a substantial portion of animals--59-79%, depending on the challenge strain and route--against moderate doses of spirochetes delivered either by injection or by bite of infected nymphal ticks (Ixodes scapularis). The instances of vaccine failure were associated with development of low levels of antibody to a particular OspA epitope, one defined by mAb LA-2. At least 50 ng ml-1 of LA-2 equivalent antibody was necessary for protection of hamsters. Lower LA-2 equivalent antibody concentrations occurred in unprotected animals in the presence of high-titered polyclonal antibody to native OspA. A competitive binding assay to quantitate this serum fraction is described that should be of use in monitoring the quality of the antibody response to OspA in vaccine trials. Concentrations of LA-2 equivalent antibody parallel the ability of the serum specimens to inhibit the growth of B. burgdorferi in culture.

Animals↗

Seroepidemiology of infections due to spotted fever group rickettsiae and Ehrlichia species in military personnel exposed in areas of the United States where such infections are endemic.

A prospective, seroepidemiologic study of spotted fever group rickettsiae (SFGR) and Ehrlichia infections was done among 1194 US military personnel exposed in a heavily tick-infested area of Arkansas in 1990. Seroconversion (4-fold) and seroprevalence rates were determined by indirect immunofluorescent antibody assays. Seroconversions to SFGR occurred in 30 persons (2.5%), whereas seroconversion to Ehrlichia species occurred in 15 (1.3%). The majority of seroconverters did not report symptoms (22/30 [73%] of SFGR seroconverters; 10/15 [67%] of Ehrlichia species seroconverters). History of tick attachment was associated with seroconversion to SFGR (relative risk [RR] = 4.3, P < .001) and Ehrlichia species (RR = 3.6, P < .05). Use of permethrin-impregnated uniforms significantly decreased risk of infection (P < .01); use of bed nets increased risk by 4-fold. Tickborne infections represent a significant threat to military personnel training in areas in which these infections are endemic.

Adolescent↗

Clinical and immune responses of tuberculosis patients treated with low-dose IL-2 and multidrug therapy.

The immune response to infection with M. tuberculosis depends on cytokine activation of effector cells. We therefore conducted a pilot study of recombinant human interleukin-2 (rhuIL-2) as an adjunct to multidrug therapy (MDT) to evaluate the safety of this approach and to determine whether IL-2 can enhance the cellular immune response in patients with pulmonary tuberculosis (TB). Patients included in this study presented with a wide range of extent and duration of infection, and were grouped into three categories for data analysis: (1) patients with newly diagnosed, acute-stage TB who were just beginning MDT; (2) patients who had received a minimum of 45 days MDT before the start of the study and who had responded to treatment; and (3) patients with multidrug-resistant (MDR) TB who had been on MDT for at least seven months without apparent beneficial clinical response. Twenty patients received 30 days of twice-daily intradermal injections of 12.5 micrograms of IL-2. Patients from all three groups showed improvement of clinical symptoms over the 30-day period of treatment with IL-2 and MDT. Results of direct smear for acid fast bacilli (AFB) demonstrated conversion to sputum-negative following IL-2 and MDT treatment in all newly diagnosed patients and in 5/7 MDR TB patients. (The size of the skin test response to purified protein derivative (PPD) of tuberculin increased during the 30-day IL-2 adjunctive therapy in newly diagnosed patients, but decreased or disappeared in the other two groups of treated patients.) Assays in vitro for phenotype distribution, natural killer (NK) cell activity, frequency of cells proliferating in response to exogenous IL-2, and antigen-induced blastogenesis demonstrated systemic responses to intradermally administered rhuIL-2. Levels of interferon-gamma (IFN-gamma) in plasma, peripheral blood mononuclear cell (PBMC) IFN-gamma mRNA and IFN-gamma mRNA in biopsy of site of skin test response to purified protein derivative (PPD) were highest in those patients with the most acute symptoms at the beginning of the study, and decreased during rhuIL-2 and MDT. IL-2 immunotherapy did not modify levels of mRNA expression for other cytokines. Patients receiving IL-2 did not experience clinical deterioration or significant side effects. These results suggest that IL-2 administration in combination with conventional MDT is safe and may potentiate the antimicrobial cellular immune response to TB.

Adult↗

D1- and D2-receptor mediation of motoric behavior in rats depleted of DA as neonates: effects of age and size of depletion.

The D1/D2 mediation of motor behavior in rats is qualitatively altered following large forebrain dopamine (DA) depletions on postnatal day 3. These animals are markedly subsensitive, relative to controls or animals depleted of DA as adults, to the motoric deficits produced by individual D1- or D2-like antagonists but are impaired following combined D1 +D2 antagonists. In order to determine the extent of DA depletion necessary to produce this subsensitivity to individual antagonists, we compared the motoric effects of D1 and D2 antagonists in adult animals sustaining a wide range of DA depletions on day 3. Only animals with striatal depletions of > or = 95% demonstrated this subsensitivity to individual antagonists. Moreover, since important changes in DA receptor ontogeny occur during the first postnatal week, we compared the ability of the D1-like antagonist, SCH 23390 (0.2 mg/kg), or the D2-like antagonists, clebopride (10.0 mg/kg) and haloperidol (1.0 mg/kg), to induce akinesia or catalepsy in adults depleted of DA on either day 1 or on day 3. Rats depleted of striatal DA (> 95%) at either age exhibited similar subsensitivity to D1 or D2 antagonists. These findings suggest that large DA depletions are necessary to alter the roles of D1 and D2 receptors in the expression of motor behavior and that this plasticity is comparable in animals depleted on day 1 or day 3.

Aging↗

Animal models of Lyme disease: pathogenesis and immunoprophylaxis.

Valuable insights into the pathogenesis and immunoprophylaxis of Lyme disease are beginning to emerge from studies in animal models. This review highlights two animal models: the mouse, which has allowed us to investigate the role of both the immune response and spirochete phenotype in determining the outcome of the disease; and the Rhesus monkey, which manifests signs of nerve involvement, in addition to showing erythema migrans and arthritis.

Animals↗

Discovery of an enzootic cycle of Borrelia burgdorferi in Neotoma mexicana and Ixodes spinipalpis from northern Colorado, an area where Lyme disease is nonendemic.

An intensive enzootic cycle of Borrelia burgdorferi was seen in populations of the Mexican wood rat, Neotoma mexicana, and Ixodes spinipalpis ticks in northern Colorado. Cultures of rodent ear tissue and ticks yielded 63 spirochetal isolates: 38 N. mexicana, 2 Peromyscus difficilis, and 23 I. spinipalpis. All 63 isolates were identified as B. burgdorferi sensu lato by polymerase chain reaction; a representative subset was characterized as B. burgdorferi by SDS-PAGE and immunoblotting. A tick-derived spirochete isolate was infectious to laboratory mice and I. scapularis, the principal vector of Lyme disease in endemic areas of the United States. The risk of human contact with infected I. spinipalpis appears to be minimal from this epidemiologically silent focus in northern Colorado, since this tick is restricted to wood rat nests in this semiarid environment.

Animals↗

Causes of death in racehorses over a 2 year period.

Necropsies were performed on 496 horses that had a fatal injury or illness at a California racetrack during the period February 20th 1990 to March 1st 1992. The primary cause of death was categorised by breed, activity at time of injury or illness and organ system affected. Most of the submissions were Thoroughbred horses (432) and Quarter Horses (46). Most of the injuries occurred while racing (42%) and in training sessions (39%); with fewer non-exercise (12%) and accident (7%) related injuries or illnesses. Musculoskeletal injuries accounted for 83% of the Thoroughbred and 80% of the Quarter Horse submissions. The Thoroughbred horses incurred 306 fractures with 263 in the limbs and 90% of those in the forelimbs. The proximal sesamoid bone(s), third metacarpal bone and humerus were the most common bones fractured in Thoroughbred horses and Quarter Horses. Other major causes of death included respiratory, digestive and multi-organ system disorders.

Age Factors↗

Cytokine gene expression by cultures of human lymphocytes with autologous Mycobacterium tuberculosis-infected monocytes.

In order to better understand the immunoregulation following Mycobacterium tuberculosis infection, cytokine mRNA induction in response to in vitro infection of human monocytes with live virulent M. tuberculosis H37Rv cocultured with autologous lymphocytes was quantitated by reverse transcriptase-PCR. Induced levels of interleukin 1 beta (IL-1 beta), IL-2, tumor necrosis factor alpha, and gamma interferon (IFN-gamma) were compared among groups of individuals representing three phases of immunity to infection with M. tuberculosis: naive normal control subjects, purified protein derivative (PPD)-reactive normal donors, and individuals with active tuberculosis (TB [diseased]). Levels of IL-1 beta and tumor necrosis factor alpha mRNA in cocultured cells from TB patients were 51 and 45%, respectively, of those obtained in cells from sensitized healthy volunteers and were comparable to those from naive normal donors. Lymphoproliferative responses to M. tuberculosis and induction of the T-cell cytokine IL-2 were predictably high in the cells of PPD-sensitized donors, low in normal naive individuals, and variable among TB patients. In contrast, the induced level of another lymphokine, IFN-gamma, did not follow the pattern seen in IL-2 induction. Infection with live M. tuberculosis induced high levels of IFN-gamma mRNA in lymphocytes of both PPD-sensitized and normal naive donors compared with those of TB patients. Interestingly, polyclonal stimulation with the mitogen concanavalin A induced similar IFN-gamma levels in cells from all three donor groups. The high level of IFN-gamma induced by the infection of monocytes from naive normal donors suggests a role for natural killer (NK) cells in the production of IFN-gamma in this coculture system. This response appears independent of the role performed by T cells.

Adult↗

The major histocompatibility complex-restricted response of recombinant inbred strains of mice to natural tick transmission of Borrelia burgdorferi.

The causative agent of Lyme disease, Borrelia burgdorferi, is transmitted by ticks of the Ixodes ricinus complex. In this study, we report the antibody response of recombinant inbred strains of mice of the H-2, b, d, and k haplotypes, infected with B. burgdorferi as a result of exposure to infected I. dammini. The patterns of antibody response assayed by Western blot analysis indicate significant major histocompatibility complex (MHC) restriction to bacterial antigens within the first 2 mo of infection in mice. Other bacterial antigens induce a significant response across the MHC haplotypes tested when assayed on the same bacterial strain used to transmit the infection, but do not crossreact with the same proteins derived from heterologous strains of B. burgdorferi. No response to outer surface protein A was detected at any time during the 60-d period we analyzed this infection. A third group of bacterial antigens appear to generate a MHC-nonrestricted response, and this lack of restriction is maintained when assaying the crossreactivity of the response with other strains of B. burgdorferi. These proteins may provide more accurate diagnostic probes than those currently in use. Finally, there appears to be a significant difference in the expression of most bacterial antigens when the spirochete is cultured for many passages since the same strain of bacterium isolated from low-passage and high-passage preparations exhibit different banding patterns in Western blots when assayed with the same sera.

Animals↗

Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans.

We demonstrate that Borrelia burgdorferi infection in the rhesus monkey mimics the early and early disseminated phases of human Lyme disease. Clinical, bacteriological, immunological, and pathological signs of infection were investigated during 13 weeks after inoculation of the spirochete. Three animals were given B. burgdorferi (strain JD1) by needle inoculations, six animals were exposed to the bite of B. burgdorferi-infected Ixodes dammini ticks, and three animals were uninfected controls. B. burgdorferi could be recovered from all animals that were given the spirochete. Bacteria were detectable until week 6 postinoculation (p.i.) in blood, until week 8 p.i. in skin biopsies, and at 10 weeks p.i. in the conjunctiva of one of two animals which developed conjunctivitis. Erythema migrans (EM) appeared in one of the three animals infected by needle inoculation and in five of the six animals infected by ticks. Deep dermal perivascular lymphocytic infiltrations (characteristic of human EM) were observed in all animals showing EM clinically. Both EM and conjunctivitis were documented concomitantly with the presence of the spirochete. Lethargy, splenomegaly, and cerebrospinal fluid pleocytosis were also noted in some animals, but the direct connection of these signs with the infection was not shown. The appearance rate of immunoglobulin M and immunoglobulin G antibodies to B. burgdorferi, as well as the antigen spectra recognized, were remarkably similar to those seen in humans. Serum antibodies from infected animals were able to kill B. burgdorferi in vitro in the presence of rhesus complement. The rhesus monkey model appears to be useful for the investigation of the immunology and pathogenesis of Lyme disease and for the development of immunoprophylactic, diagnostic, and chemotherapeutic protocols.

Animals↗

Eosinophilic mediastinitis, myositis, pleuritis, and pneumonia of cattle associated with migration of first-instar larvae of Hypoderma lineatum.

Migrating first-instar larvae of Hypoderma lineatum are a frequent cause of focal inflammatory lesions in connective tissues of the mediastinum, parietal and visceral pleura, peritoneum, lungs, diaphragm, and other loci. The lesions are characterized grossly by foci of yellowish or greenish gelatinous edema and microscopically by infiltration of the edematous tissue by a dense array of eosinophils. Lesions were recognized during a period of several weeks in late spring; the timing was attributable to events in the life cycle of the fly. The larvae, which were small (approximately 1 x 4.5 mm), transparent, and unobtrusive, were recovered from lesions in 12 of 20 cattle in which careful parasitologic examination was made.

Animals↗

Amblyomma americanum: a potential vector of human ehrlichiosis.

Polymerase chain reaction primers specific for Ehrlichia chaffeensis were used to amplify DNA from extracts of pooled ticks. Amplification was performed on extracts from 140 pools (1,579 total ticks) consisting of three tick genera collected from five states. The characteristic 389-basepair product was observed after amplification of extracts from seven different pools of adult Amblyomma americanum (117 pools, 1,462 ticks), but not from pools of nymphs. No specific product was observed after amplification of 20 pools (105 ticks) of Dermacentor variabilis and three pools of Ixodes scapularis (12 ticks). Ehrlichia chaffeensis was present in A. americanum at a minimum frequency of > or = 0.48%, suggesting that A. americanum may be a vector of human ehrlichiosis.

Animals↗

The hamster immune response to tick-transmitted Borrelia burgdorferi differs from the response to needle-inoculated, cultured organisms.

The human immune response to natural infection with Borrelia burgdorferi appears to differ from that seen in small mammals infected by needle inoculation. In humans, antibody to outer surface proteins A and B (OspA and OspB) is not detectable until late in infection, but small mammals inoculated with B. burgdorferi produce early antibody to OspA and OspB. To investigate this disparity we compared the immune response in hamsters to B. burgdorferi after needle inoculation with cultured organisms or infected tick homogenates with the immune response after tick transmitted (natural) infection. We determined that the antibody response to OspA and OspB after natural infection of hamsters is similar to that seen in humans, and differs from the antibody response after hamster infection by needle inoculation. High titers of antibody to OspA and OspB were undetectable even 42 wk after bite by B. burgdorferi-infected ticks. The failure to produce antibody to OspA and OspB was not dependent on challenge dose, because animals inoculated by needle with low doses (1 x 10(5) to 1 x 10(6) cells) of B. burgdorferi produced antibody to OspA and OspB. A rapid but limited anti-41-kDa response was observed. One possible new Ag, 43 kDa (p43), was identified. The antibody response to p43 was independent of the route of inoculation. Our results suggest that the hamster immune response to tick-transmitted Borrelia burgdorferi differs from the response to needle inoculated, cultured organisms.

Animals↗

D-1 and D-2 receptor mediation of sensorimotor behavior in rats depleted of dopamine during development.

The effects of selective D-1 and D-2 antagonists on sensorimotor behavior were studied in rats treated with 6-OHDA or its vehicle solution on either postnatal day 3, 20, or 35. Blockade of either D-1 or D-2 receptors induced akinesia and somatosensory neglect in adults treated with vehicle at any of the three ages. The behavioral effects of antagonists on rats with 6-OHDA-induced dopamine depletions varied as a function of the age at the time of damage. Adults depleted of DA on Day 35 exhibited behavioral deficits after either D-1 or D-2 blockade and at doses that were ineffective in controls. Adults depleted of DA on Day 20 exhibited deficits after either D-1 or D-2 blockade but were not any more sensitive than were controls. In contrast, adults depleted of DA on Day 3 were insensitive to the behavioral effects of D-1 or D-2 blockers but were impaired after the dual administration of both antagonists. Moreover, simultaneous administration of subthreshold doses of D-1 and D-2 antagonists produced behavioral deficits in controls and rats depleted on Day 3. These data demonstrate that activity within residual DA neurons remains critical for the expression of sensorimotor behavior in rats depleted of DA during development. However, the specific contribution of D-1 and D-2 receptors to these behaviors depends upon the animals' age at the time of depletion.

Afferent Pathways↗

Bovine abortions attributable to Listeria ivanovii: four cases (1988-1990).

During a 3-year period, 4 cases of bovine abortion attributable to Listeria ivanovii were diagnosed from 243 bovine fetuses submitted for diagnostic evaluation. Listeria monocytogenes was isolated only once from a bovine fetus during this same time period. Pathologic findings were similar to those seen in abortions attributable to L monocytogenes. Consistent management factors were not recognized and breed susceptibility was not apparent. Listeria ivanovii is most often associated with abortions from sheep and is rarely reported from cattle. On the basis of findings in this study, L ivanovii must be included as a potential cause of bovine abortions.

Abortion, Veterinary↗