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Biomedical subjects

B Roberts

Publications and source records attributed to B Roberts.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1996

Magnetoencephalographic assessment of spontaneous brain activity in schizophrenia.

Magnetoencephalography (MEG) offers an attractive alternative to electroencephalography (EEG) in the assessment of psychiatric patients. In this study, a whole-head biomagnetometer equipped with 122 super-cooled sensors was used to assess spontaneous neuromagnetic activity in 11 unmedicated schizophrenic patients and 8 schizophrenic patients medicated for more than 8 weeks with novel antipsychotics (5 of whom were initially studied as part of the unmedicated group). Ten normal (nonpsychiatric) controls were also examined. For each subject, 5 minutes of data were collected in an eyes-closed state. Data were visually inspected for gross MEG abnormalities, and average power spectra were calculated for the data at each sensor. No gross abnormalities were identified for control subjects. One unmedicated schizophrenic patient showed epileptiform sharp waves, and 4 showed abnormal slow waves. No gross MEG abnormalities were found for the medicated schizophrenic group (which included 3 patients who had previously shown slow waves in the unmedicated state). Spectral analyses showed that the schizophrenia patients demonstrated lower alpha power and peak frequency than controls. The data are interpreted within the context of previously reported magnetic resonance abnormalities of the thalamus.

Adult↗
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↗
PubMed1995

Evidence of apoptotic cell death in HIV encephalitis.

The mechanism of cell death in the brains of patients with acquired immune deficiency syndrome was examined in 15 cases, 8 of whom had human immunodeficiency virus (HIV) encephalitis, and in 8 control cases. Postmortem formalin-fixed, paraffin-embedded sections were prepared for routine histology and immunohistochemistry to detect cell-specific antigens. Apoptosis was detected by its morphology and by in situ end labeling of its characteristic oligonucleosomal fragments. Combined in situ end labeling and immunohistochemistry identified specific cell types. Six acquired immune deficiency syndrome brains, 5 of which had HIV encephalitis, contained positive nuclei by in situ end labeling. Co-labeling studies identified the cells as neurons, reactive astrocytes, and, rarely, the multinucleated giant cells of HIV encephalitis. The only control with nuclei positive by in situ end labeling had hepatic encephalopathy and Alzheimer type II astrocytes; the location and absence of cell-specific markers suggested a glial origin for the labeled cells. These results demonstrate that at least some neuronal and astrocytic death in HIV infection occurs by apoptosis. Its stimuli are unknown, but likely candidates include tumor necrosis factor or HIV viral products. Additionally, we hypothesize that apoptotic death of reactive astrocytes may be a normal mechanism whereby the brain removes an excess number of astrocytes that have proliferated after certain types of brain injury.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Glutathione-linked detoxification pathway in normal and malignant human bladder tissue.

This study compares the levels of glutathione (GSH) and GSH-dependent detoxification enzymes, which have been implicated in anti-cancer drug resistance, in paired normal and malignant human bladder tissues, a tumor with high incidence of inherent drug resistance. Although the mean GSH transferase (GST) activity did not differ significantly in normal and neoplastic bladder tissues, this enzyme activity was relatively higher in tumor tissues of five out of ten patients as compared with corresponding normal tissues. Similarly, the mean GSH content and GSH reductase activity did not differ significantly between normal and neoplastic bladder tissues. On the other hand, the mean GSH peroxidase activity towards cumene hydroperoxide and catalase activity in bladder tumors was higher by about 1.5 and 1.4 times, respectively (P < 0.05), compared with those of normal tissues. GST isoenzymes corresponding to the three major classes (alpha, mu and pi) were expressed in every normal bladder tissue examined in the present study. Overexpression of GST pi was observed in 60% of the bladder tumors, whereas alpha and mu type GST proteins in tumor tissues were lower at frequencies of 62.5% and 37.5%, respectively, compared with the corresponding normal tissues. These results suggest that (a) elevated levels of GSH peroxidase, catalase and GST pi in human bladder tumors may contribute, at least in part, to the intrinsic drug resistance of this neoplasm and (b) anti-oxidative enzymes GSH peroxidase and/or catalase may represent markers for this neoplasia, although a large number of tissue specimens must be analyzed to validate this hypothesis.

Adult↗
PubMed1994

Popliteal artery aneurysms: current management and outcome.

PURPOSE: Thrombosis of popliteal artery aneurysms can produce limb-threatening ischemia. In this setting we have found preoperative thrombolytic therapy to be beneficial. METHODS: Thirty-three patients with 54 popliteal artery aneurysms were studied (mean follow-up 62 months). Twenty-one patients (62%) had bilateral popliteal artery aneurysms, and 20 patients (61%) had extrapopliteal arterial aneurysms. Thirty-three (61%) aneurysms had symptoms of compression or ischemia, and 21 (39%) aneurysms had thrombosis. A trend toward thrombosis for larger aneurysms was noted (p < 0.068). RESULTS: Forty-five aneurysms were treated with bypass grafting. Five-year graft patency and limb salvage rates were 71% and 90%, respectively. Factors favoring graft patency and limb salvage included presence of two- or three-vessel runoff compared with patients with single- or no-vessel runoff (p < 0.025 graft patency; p < 0.003 limb salvage) and presence of a patent aneurysm (p < 0.005 graft patency and limb salvage). Seven patients diagnosed with thrombosis of their aneurysm and all runoff vessels were treated with preoperative thrombolytic therapy. Complete clearing of thrombus from these arteries was achieved in six of these patients (and from two of these runoff vessels in the remaining patient). These patients had better graft patency (p < 0.005) and limb salvage (p < 0.01) than comparable patients treated with emergency operations. Six amputations were performed in the follow-up interval, none of which were performed in patients having undergone thrombolytic therapy. CONCLUSIONS: It is concluded that popliteal aneurysms are managed best by elective repair of patent aneurysms with good runoff. In that difficult situation of the thrombosed popliteal artery aneurysm associated with acute leg ischemia, thrombolytic therapy safely and effectively provides patients with a more favorable alternative than emergency surgery.

Adult↗
PubMed1994

Induction of human tissue plasminogen activator in the mammary gland of transgenic goats.

Three transgenic females from a first generation transgenic male were induced to lactate between 11 and 12 months of age using a series of estrogen and progesterone injections. The milk contained human longer acting tissue plasminogen activator (LAtPA) at comparable concentrations (1-3 mg/ml) as occurred in the original founder female. In addition, the transgenic male was induced with a hormonal regime and was shown to produce 0.85 mg/ml of LAtPA. Milk protein gels indicated that the milk products (casein, IgG) were essentially normal. These experiments show that expression data for this vector can be evaluated in a shorter period of time in dairy goats than would be required through normal gestation and lactation schedules and can be used to identify the relative expression of transgenes in mammary tissue that would occur during normal lactation.

Animals↗
PubMed1994

Comparison of live attenuated and inactivated influenza vaccines in cystic fibrosis patients and their families: results of a 3-year study.

Forty-one cystic fibrosis (CF) patients and 89 family members were immunized in a double-blind randomized 3-year trial with either intranasal live cold-adapted (ca) influenza A vaccine or the recommended intramuscular trivalent inactivated (triv) influenza vaccine. Local, respiratory, and systemic symptoms after vaccine were infrequent and did not differ between vaccine groups. CF patients did not differ from family members in immune response to either vaccine. Although antibody responses tended to be higher after triv vaccine, > or = 85% of subjects had mean hemagglutination inhibition antibody titers > or = 1:32 to influenza H1N1 and H3N2 after the first dose of either vaccine. Infection with influenza H3N2 viruses circulating during this study occurred with comparable low frequency in CF patients after ca (14 infections/100 subject-years of observation) or triv vaccine (10 infections/100 subject-years of observation). Influenza A ca vaccines appear to be safe, immunogenic alternatives to influenza A inactivated vaccines for CF patients and their families.

Adolescent↗
PubMed1994

Prevalence of HTLV types I and II among drug users in King County, Washington.

We investigated the prevalence of human T-cell lymphotropic virus (HTLV) types I and II among drug users entering treatment in King County, Washington, between 1988 and 1990. Of 762 injection-drug users, 81 (10.6%) were HTLV-positive; of 89 noninjection-drug users, 2 (2%) were HTLV-positive. Most (95.8%) of those typed) were HTLV-II-positive. The relationship between HTLV and demographic and behavioral characteristics was further evaluated among injection-drug users. The prevalence rates for HTLV increased 25-fold from the youngest age group (15 to 24 years) to the oldest (older than 45 years), after adjusting for race. After adjustment for age, American Indians or Alaska Natives were 7.9 times, blacks 6.2 times, Asians or Pacific Islanders 4.7 times, and Hispanics 4.1 times as likely as whites to be HTLV-positive. The prevalence of HTLV among heroin injectors was more than double that observed among injectors of other drugs after adjusting for age, although this association was only marginally significant. The strong association between HTLV prevalence and age suggests that HTLV-II (the predominant virus) has been endemic among King County injection-drug users for some time. Its relatively high prevalence indicates that there is both an opportunity and a need to further investigate the epidemiologic and clinical implications of HTLV-II infection.

Adolescent↗
PubMed1993

Identification and quantification of juvenile hormone biosynthesized by larval and adult Australian sheep blowfly Lucilia cuprina (Diptera: Calliphoridae).

Recent evidence indicates that higher dipterans biosynthesize predominantly the novel juvenile hormone (JH) bisepoxide, methyl (2E,6trans)-6,7,10,11-bisepoxy-3,7,11-trimethyl-2-dodecen oate (JHB3), together with a small proportion of methyl (2E,6E)-10,11-epoxy-3,7,11-trimethyl-2,6-dodecadienoate (JHIII) and possibly its 6,7-epoxy isomer. A strategy of gas chromatography-mass spectrometry (GC-MS) involving cool on-column GC and negative-ion chemical ionization MS has enabled the selective analysis of underivatized JH-like products released in vitro by ring glands and corpora allata of Lucilia cuprina. JHB3 is released to the exclusion of mono-epoxidized and unepoxidized esters. The rate of JHB3 release in adult females increases dramatically after protein feeding from 0.2 to 5.2 pmol/h/gland. Values agree well with the rate of JH biosynthesis determined by radiochemical assay. As revealed by thin-layer chromatography, the radiolabel is predominantly incorporated into JHB3, of which only 2% is retained in the corpus allatum indicating almost immediate release from the gland. Approximately 5% of radioactive material retained in the glands co-migrates with JHIII and may be an intermediate in JHB3 synthesis. We conclude that JHB3 is the only juvenile hormone biosynthesized in vitro by L. cuprina. The data suggest that JHB3 may be the exclusive JH synthesized by higher dipterans.

Animals↗