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Biomedical subjects

B Roberts

Publications and source records attributed to B Roberts.

At least 19 recordsLinked to original sources
PubMed1996

Utility of SHIV for testing HIV-1 vaccine candidates in macaques.

SUMMARY: Intravenous injection of SHIV (simian/human immunodeficiency virus, chimeric virus) into rhesus macaques resulted in a viremia in peripheral blood lymphocytes (PBL) and the generation of anti-HIV-1 (human immunodeficiency virus type 1) envelope immune responses. A challenge stock of a SHIV containing HIV-1 HXBc2 envelope glycoproteins was prepared from infected rhesus monkey peripheral blood mononuclear cells (PBMC). The minimum animal infectious dose of the SHIV stock was determined and used in a challenge experiment to test protection. The vaccination of two rhesus monkeys with whole inactivated HIV-1 plus polydicarboxylatophenoxy phosphazene (PCPP) as the adjuvant protected the animals from becoming infected by a SHIV challenge. This experiment demonstrated for the first time that monkeys immunized with HIV-1 antigens can be protected against an HIV-1 envelope-containing virus. As the challenge virus was prepared from monkey PBMC, human antigens were unlikely to be involved in the protection. Protection of rhesus monkeys from SHIV challenge may help,define protective immune responses stimulated by HIV-1 vaccine candidates.

AIDS Vaccines↗
PubMed1996

Spectral regularity as a factor distinct from harmonic relations in auditory grouping.

When the regular spectral pattern formed by an odd-harmonic complex (the base) is disrupted by an added even harmonic, the added component is judged as more salient than its neighbors. This study considered whether the effects of spectral pattern on perceptual segregation are restricted to harmonic stimuli. Participants either rated the clarity or judged the relative pitch of a cued component in a series of complex tones. The difference in clarity between added and base components found for the harmonic complexes was not reduced when the complexes were made inharmonic either by a frequency shift or by spectral stretch or compression. However, the added-base difference could be abolished for an inharmonic complex when the distribution of components across frequency was made uniform. These findings suggest that spectral regularity is a factor distinct from harmonic relations in auditory grouping.

Attention↗
PubMed1996

Light and electron microscopic identification of Cyclospora species in the small intestine. Evidence of the presence of asexual life cycle in human host.

This is the first case of cyclosporiasis in which the parasite was clearly demonstrated in a duodenal biopsy by light microscopy. Electron microscopy identified the stages of sporozoite, trophozoite, schizont, and merozoite. Although only asexual forms were identified in our case, the sexual cycle must have taken place in the human host, because oocysts were detected in stools of the patients. Therefore, it appears that Cyclospora species require only a single host to complete its entire life cycle. Despite the heavy infection, only enterocytes were invaded. The lamina propria and submucosa were not involved. The morphology of Cyclospora in the intestine is similar to that of Isospora, but differs from that of Cryptosporidium. The morphology of the oocyst of Cyclospora resembles that of Cryptosporidium, but differs from that of Isospora. Thus, a combined study of both stool and intestinal biopsy should readily distinguish Cyclospora from Cryptosporidium and Isospora.

AIDS-Related Opportunistic Infections↗
PubMed1996

Identification and characterisation of a superoxide dismutase and catalase from Mycobacterium ulcerans.

Previous investigations have demonstrated the presence of both superoxide dismutase and catalase enzymes in several intracellular pathogens, including a number of mycobacterial species. These enzymes are believed to be involved in the protection of the pathogen from the bactericidal products of oxidative metabolism. Superoxide dismutase and catalase were identified in crude extracts of Mycobacterium ulcerans by polyacrylamide gel electrophoresis. Inhibition experiments showed that the superoxide dismutase probably contained manganese as the metal cofactor. Other mycobacterial species examined for comparison produced bands of superoxide dismutase activity with a different mobility to that of M. ulcerans, suggesting possible structural differences between the enzymes.

Azides↗
PubMed1996

Assessment of stimulated and spontaneous adrenocorticotropin secretory dynamics identifies distinct components of cortisol feedback inhibition in healthy humans.

Corticosteroids inhibit ACTH secretion through diverse cellular mechanisms, including direct pituitary and indirect suprapituitary effects. Although exogenous CRH provides a useful assessment of corticotroph function, the suprapituitary component of ACTH regulation has been difficult to assess in humans. Naloxone (NAL) has been reported to stimulate ACTH secretion indirectly through the release of endogenous hypothalamic CRH, suggesting its potential application in the examination of suprapituitary regulation of ACTH secretory dynamics. We sought to examine the inhibitory effects of corticosteroids on kinetic parameters of ACTH secretion, assessed by a deconvolution method, in healthy human subjects. We also sought to directly compare the ACTH responses to serial administration of human CRH and NAL as well as spontaneously occurring ACTH pulses to distinguish pituitary and suprapituitary components of hypothalamic-pituitary-adrenal regulation. Normal healthy subjects (n = 11) received hCRH (0.4 microgram/kg) at 1800 h and then NAL (65 micrograms/kg) at 1930 h, respectively, on 3 separate study days: placebo pretreatment plus CRH/NAL stimulation, metyrapone (MET) pretreatment plus CRH/NAL, or MET alone. Plasma ACTH and serum cortisol were assessed at frequent (every 10 min) intervals during CRH/NAL or placebo infusions (1800-2100 h) on all 3 study days, and deconvolution analysis was performed to determine kinetic parameters of endogenous and stimulated ACTH secretion. Suppression of endogenous cortisol secretion with MET significantly increased both continuous (basal secretion rate) and pulsatile CRH- and NAL-stimulated ACTH bursts (P < 0.05). The increase in total ACTH secreted per burst was related to two distinct effects of cortisol regulating the amplitude (maximum secretion rate) and half-duration (P < 0.05) of secretory bursts. The ACTH responses to CRH and NAL for individual subjects were significantly and positively correlated in both placebo pretreatment plus CRH/NAL stimulation and MET pretreatment plus CRH/NAL studies (P < 0.01). MET administration disproportionately increased the ACTH response to NAL, producing a significant increase (P < 0.01) in the slope of the regression relating ACTH responses to CRH and NAL. The following conclusions were made: 1) endogenous cortisol secretion, even at levels associated with relatively low serum cortisol concentrations, exerts a significant negative feedback effect on both continuous and pulsatile ACTH secretion; 2) cortisol inhibits pulsatile ACTH secretion through distinct regulatory mechanisms that independently modulate both the mass and the duration of ACTH secretory bursts; 3) the differential sensitivity of the CRH- and NAL-stimulated ACTH responses to MET administration suggests that both pituitary and suprapituitary components of the hypothalmic-pituitary-adrenal axis are sensitive to negative regulation over a rapid or intermediate temporal domain. Endogenous cortisol modulates multiple components of dynamical ACTH secretion through composite effects that appear to be mediated through structurally and functionally distinct regulatory domains.

Adrenocorticotropic Hormone↗
PubMed1996

Molecular cloning of two novel transmembrane ligands for Eph-related kinases (LERKS) that are related to LERK-2.

A search of the nucleic acid database of expressed sequence tags (ESTs) revealed several partial cDNA sequences that could encode proteins homologous to the ligands for Eph-related kinases (LERKs). Oligonucleotides designed from the ESTs were used to probe a human brain cDNA library and obtain overlapping clones that encoded two different novel LERKS (NLERK-1 and NLERK-2). NLERK-1 and NLERK-2 are most closely related to human LERK-2/Elk-ligand and they form a subclass of LERKs that contain a transmembrane domain and a conserved cytoplasmic domain. Full-length NLERK-1 was expressed as a glycosylated membrane protein in COS cells and was not secreted into the medium. Full-length NLERK-2 was similarly expressed in COS cells but both membrane-bound and a truncated, proteolytically-released form were detected. Engineered forms of both NLERK-1 and NLERK-2 lacking transmembrane and cytoplasmic domains were also expressed in COS cells and each was detected in the extracellular medium.

Amino Acid Sequence↗
PubMed1996

Regularity of spectral pattern and its effects on the perceptual fusion of harmonics.

A single even harmonic added to an odd-harmonic complex may be judged as perceptually more salient than the odd harmonics themselves (Roberts & Bregman, 1991). It is proposed that this effect occurs because the even harmonic is inconsistent with the regular spectral pattern formed by the odd-harmonic complex (the base). Therefore, a reduction in the regularity of the base spectrum should reduce the even-odd difference. Spectral regularity was reduced either by removing base components, or by including components in the base that were inconsistent with its original pattern. Subjects listened to (primarily) harmonic complex tones and rated the clarity of one of the harmonics, cued by a preceding pure tone. Both removing components from the base and including extraneous components in the base reduced the even-odd difference. The results suggest that it is easier to segregate a harmonic from a periodic complex tone when it does not form part of the regular pattern of spectral spacing defined by the other harmonics.

Attention↗
PubMed1996

Murine flt3 ligand protects M1 leukemic cells from LIF-induced differentiation and suppression of self-renewal.

Self-renewing cell divisions are an important characteristic exhibited by both normal hematopoietic stem cells and leukemic cell populations. We have examined the action of flt3/flk2 ligand (FL) on physiologic suppression of self-renewal during growth factor-induced differentiation of M1 leukemic cells. Unstimulated M1 cells expressed high levels of flt3 receptor mRNA and protein, with approximately 20,000 molecules present at the cell surface. Consistent with data obtained from normal macrophage populations, expression of both mRNA and protein for flt3 receptor was suppressed as cells were induced to differentiate into mature macrophages in response to leukemia inhibitory factor (LIF). Although FL alone had no detectable action on unstimulated M1 cells, an effect was revealed during LIF-induced differentiation. FL overcame LIF-induced suppression in clonal cultures of M1 cells, prevented morphologic changes associated with macrophage differentiation and interfered with the LIF-induced responsiveness of M1 cells to macrophage colony-stimulating factor (M-CSF). This action of FL was evident on both parental M1 cells and M1 cells whose differentiation program was perturbed by enforced expression of the transcription factor SCL. The action of FL was most striking in clone transfer experiments in which FL rescued M1 cells from LIF-induced suppression of self-renewal. The ability of FL to maintain self-renewal characteristics satisfies one of the criteria predicted for a stem-cell-active molecule and contrasts with the action of FL in stimulating proliferation and differentiation of normal hematopoietic cells.

Animals↗
PubMed1996

Reducing the use of the target animal batch safety test for veterinary vaccines.

The need to submit each batch of every veterinary vaccine to a target animal safety test is questioned. It is proposed that a risk/benefit analysis should be conducted, on a product by product basis, to determine whether the continued application of this test to each batch of a product is beneficial and justified. For an established product, the analysis should consider: the number of batches manufactured; the length of time for which the product has been manufactured; the testing experience and the incidence of reported adverse reactions; the level of GMP compliance and the standard of QA practised by the manufacturer; the method and conditions of manufacture; the use of animals for other batch tests; the recommendations for the use of the product. For a newly developed product the analysis should take into account: the safety data generated during development; the inherent risks in the product and its manufacture; the use of the other animal tests. It is suggested that the continued use of the test could be reduced on a phased basis e.g. after 10 consecutive satisfactory tests the frequency could be reduced by limiting it to the first batch of each production campaign or to every n th batch. Furthermore, the possibility of discontinuing the test altogether, for the product in question, could be considered. A return to full testing frequency would be required in the event of: a test failure; a batch related adverse reaction; introduction of a new seed; a change of manufacturer; a process of modification; a specification amendment; or an interruption of batch continuity. When a manufacturer has established consistency of production and testing, an alternative approach to the need for batch testing, with a view to avoiding or minimising the use of animals, is both desirable and possible.

Animal Testing Alternatives↗
PubMed1995

A live attenuated vaccine for the control of avian coccidiosis: trials in broiler breeders and replacement layer flocks in the United Kingdom.

Losses caused by coccidiosis are a significant problem in the rearing of breeder and layer flocks. A live vaccine has been developed that contains attenuated lines of the seven species of Eimeria that infect the chicken. The attenuated lines were derived from virulent strains by selection for earlier development in chickens. In 11 field trials, the performance of vaccinated chicks was compared with that of matched controls receiving conventional drug prophylaxis. The vaccine was given in the drinking water to 116,600 young chickens and provided excellent control of coccidiosis. The occurrence of coccidial oocysts in the litter, coccidial lesions post mortem and overt coccidiosis was markedly lower in the vaccinated birds than in the controls.

Animals↗
PubMed1995

Relation between human T-lymphotropic virus type I and neurologic diseases in Panama: 1985-1990.

Human T-cell lymphotropic virus type I (HTLV-I) is endemic in the Caribbean basin and in Japan. HTLV-II, a closely related virus, is endemic in several groups of native Americans, including Panamanian Guaymi. In Panama, a nationwide HTLV-I/II seroprevalence of 1-2% has been reported. We evaluated the frequency of HTLV-I/II infection in patients with neurologic diseases admitted to state tertiary hospitals in Panama City between 1985 and 1990. Nineteen of 322 patients with eligible diagnoses had antibodies to HTLV-I/II, 17 with HTLV-I and 2 with HTLV-II. HTLV-I was associated with spastic paraparesis (13 of 23, 56.5% versus 4 of 299, 1.3%, p < 0.001) and with cerebellar syndrome (2 of 13, 15.4%) and multiple sclerosis (2 of 54, 3.7%) (p < 0.05 for both diseases compared with subject with none of these diagnoses). The two HTLV-I infected patients with cerebellar syndrome later developed spastic paraparesis. HTLV-II infection was noted in one patient with cerebellar syndrome and one with amyotrophic lateral sclerosis. All patients with other diagnoses were seronegative. Among patients with spastic paraparesis, HTLV-I-infected patients were clinically indistinguishable from seronegative subjects. There is apparently an overlapping clinical spectrum of neurologic diseases associated with HTLV-I and HTLV-II infection.

Adolescent↗
PubMed1995

A locking endurance test for hinged sections of removable partial dentures.

In this study an apparatus is described that will open and close a hinged section of a removable partial denture. A metal framework based on a "swinglock" type of hinge and latch design was constructed. An electric motor provided the drive for the opening and closing mechanism, which when operated set the device in motion. The device and results of a test run of 12,000 opening and closing operations are discussed.

Dental Clasps↗
PubMed1995

Enduringness and change in creative personality and the prediction of occupational creativity.

Participants in a longitudinal study of women's adult development were scored at midlife on the Occupational Creativity Scale (OCS), which draws on J. L. Holland's (1985) model of vocational environments in the assessment of participants' creative achievement. College measures of cognitive-affective style and career aspirations predicted OCS scores at age 52, and consistency of creative temperament (H. G. Gough, 1992), motivation, and overall attributes of creative personality were demonstrated with both self-report and observer data over several times of testing. However, there was change along with this enduringness: Large fluctuations in creative temperament over one period of life or another were common in individuals, and OCS scores were associated with an increase in level of effective functioning over 30 years.

Adult↗
PubMed1995

Effect of postmortem interval on in situ end-labeling of DNA oligonucleosomes.

In situ end-labeling (ISEL) of DNA oligonucleosomes facilitates detection of apoptosis in tissue sections by binding labeled nucleotides to the oligonucleosomal fragments. Although ISEL is used in postmortem material, the effect of autolysis is not specifically known. Accordingly, normal rat brain and intestine were immersed in formalin after postmortem intervals (PMI) from 0 to 72 hours (h) or were fixed by perfusion with ethanol or paraformaldehyde-glutaraldehyde (PF-G). Omission of the binding enzymes or pretreatment with DNAase served as negative and positive controls. With DNA polymerase, material fixed by perfusion or by formalin immersion with PMI of O contained ISEL-positive nuclei only in apical intestinal cells and rare intravascular blood cells in brain. Postmortem intervals from 8 to 72 h did not alter this staining pattern although false-positive ISEL developed at section edges as a result of tissue drying. Terminal deoxynucleotidyl transferase gave similar results in the formalin-fixed material with PMI from 0-48 h but nonspecific nuclear labeling was increased with a PMI of 72 h and was widespread in the PF-G and ethanol-perfused material. This study shows that PMI of at least 72 h do not affect the sensitivity or the specificity of ISEL and confirm the reliability of this procedure in postmortem material. The results also indicate that false-positive ISEL occurs if the tissue is allowed to dry or if certain combinations of fixatives and binding enzymes are used.

Animals↗