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Biomedical subjects

T Hall

Publications and source records attributed to T Hall.

At least 37 records · Page 2Linked to original sources

Flank matrix attachment regions (MARs) from chicken, bean, yeast or tobacco do not prevent homology-dependent trans-silencing in transgenic tobacco plants.

The effect of flanking matrix attachment regions (MARs) on homology-dependent trans-silencing was tested using two strong trans-silencing loci. The transgenic tobacco line 271 carries at a single locus a p35S-RiN-tNos transgene which is able to silence, in trans and at the transcriptional level, the expression of any p35S-driven transgene irrespective of its position. The transgenic tobacco line 6b8 carries at a single locus a p35S-uidA-tRbcS transgene which is able to silence in trans, at the post-transcriptional level, the expression of any uidA-expressing transgene irrespective of its position. Various transgenic tobacco lines carrying a target p35S-uidA-tNos transgene, flanked on each side by MARs from chicken, bean, yeast or tobacco, were crossed with lines carrying the 271 and 6b8 loci. Expression of the target transgene was silenced in all hybrids, irrespective of the presence or absence of MAR sequences. These results therefore demonstrate that MARs are not able to protect transgene expression from strong silencing loci that act in trans.

Animals↗

Thiamine deficiency-induced disruptions in the diurnal rhythm and regulation of body temperature in the rat.

In the present study, diurnal rhythm and regulation of body temperature were monitored during and several weeks following pyrithiamine-induced thiamine deficiency (PTD group, n=8) or pairfeeding (control group, n=9). A significant decline of core body temperature and a disruption of its diurnal rhythm were observed at varying stages of PTD treatment. Following thiamine administration and return to thiamine-fortified chow, body temperature continued to fall and several days transpired before body temperature and its diurnal rhythm were returned to normal. When exposed to warm and cold environments, no significant group differences were observed in either the maximum temperature change or the time elapsed to reach maximal temperature change. Histological examination revealed necrotic lesions in thalamus and mammillary body in the PTD group characteristic of Wernicke's encephalopathy. No significant damage was observed in the medial preoptic and suprachiasmatic nuclei, brain regions involved in the regulation of body temperature and circadian rhythm. These findings suggest that hypothermia and disruption of the diurnal rhythm of body temperature can be reversed by restoration of adequate thiamine levels and are related to biochemical and physiological disturbances rather than gross structural changes.

Animals↗

Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine.

The malaria sporozoite vaccine candidate RTS,S, formulated with an oil-in-water emulsion plus the immunostimulants monophosphoryl lipid A and the saponin derivative QS21 (vaccine 3), recently showed superior efficacy over two other experimental formulations. Immunized volunteers were followed to determine the duration of protective immune responses. Antibody levels decreased to between one-third and one-half of peak values 6 months after the last dose of vaccine. T cell proliferation and interferon-gamma production in vitro were observed in response to RTS,S or hepatitis B surface antigen. Seven previously protected volunteers received sporozoite challenge, and 2 remained protected (1/1 for vaccine 1, 0/1 for vaccine 2, and 1/5 for vaccine 3). The prepatent period was 10.8 days for the control group and 13.2 days for the vaccinees (P < .01). Immune responses did not correlate with protection. Further optimization in vaccine composition and/or immunization schedule will be required to induce longer-lasting protective immunity.

Adolescent↗

High prevalence of carotid artery disease in patients with atheromatous renal artery stenosis.

BACKGROUND: Renovascular disease is the most frequently encountered secondary cause of hypertension and is one of the few potentially reversible causes of chronic renal failure. These patients are at increased risk of having cerebrovascular events following operative management for atheromatous renal-artery stenosis. We studied the prevalence of carotid-artery disease in patients with atheromatous renal-artery stenosis. METHODS: A cross-sectional study was carried out on 38 consecutive patients with atheromatous renal-artery stenosis who underwent renal-artery balloon angioplasty. Extracranial carotid atherosclerosis was assessed using a commercially available colour Doppler scanner, depending on the velocity of the peak systolic waveform in the internal carotid artery, and the internal carotid-artery/common carotid-artery ratio. RESULTS: Twenty-one patients (55.3%) had normal or mild carotid-artery disease, 10 (26.3%) had moderate, and 7 (18.4%) had severe carotid-artery disease. Nine patients had previously suffered a stroke (eight infarction, one haemorrhage) and one had multiple transient ischaemic attacks. CONCLUSIONS: Our results suggest that, in patients with atheromatous renal-artery disease severe enough to require angioplasty, 4 out of 10 appear to have moderate to severe carotid-artery disease. This may explain the increased prevalence of atherothrombotic cerebrovascular events in these patients, and also previous observations that, following operative management for atheromatous renal-artery stenosis, some patients had developed an acute or late cerebrovascular event. We suggest therefore that such patients should always be regarded as having generalized vascular disease not confined to one system, and need to be assessed for carotid-artery disease prior to operative management for atheromatous renal-artery stenosis.

Aged↗

Elastic moduli of breast and prostate tissues under compression.

To evaluate the dynamic range of tissue imaged by elastography, the mechanical behavior of breast and prostate tissue samples subject to compression loading has been investigated. A model for the loading was validated and used to guide the experimental design for data collection. The model allowed the use of small samples that could be considered homogeneous; this assumption was confirmed by histological analysis. The samples were tested at three strain rates to evaluate the viscoelastic nature of the material and determine the validity of modeling the tissue as an elastic material for the strain rates of interest. For loading frequencies above 1 Hz, the storage modulus accounted for over 93 percent of the complex modulus. The data show that breast fat tissue has a constant modulus over the strain range tested while the other tissues have a modulus that is dependent on the strain level. The fibrous tissue samples from the breast were found to be 1 to 2 orders of magnitude stiffer than fat tissue. Normal glandular breast tissue was found to have an elastic modulus similar to that of fat at low strain levels, but the modulus of the glandular tissue increased by an order of magnitude above fat at high strain levels. Carcinomas from the breast were stiffer than the other tissues at the higher strain level; intraductal in situ carcinomas were like fat at the low strain level and much stiffer than glandular tissue at the high strain level. Infiltrating ductal carcinomas were much stiffer than any of the other breast tissues. Normal prostate tissue has a modulus that is lower than the modulus of the prostate cancers tested. Tissue from prostate with benign prostatic hyperplasia (BPH) had modulus values significantly lower than normal tissue. There was a constant but not significant difference in the modulus of tissues taken from the anterior and posterior portions of the gland.

Adult↗

Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein-1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure. Passive transfer of rabbit anti-MSP-1(19) failed to protect against homologous or heterologous challenge and, when compared with negative controls, there were no differences in prepatent periods or time to treatment. Interestingly, rabbit anti-MSP-1(19), but not anti-Pfs25, immunoglobulin, and immune monkey serum prevented the development of antibodies directed against MSP-1(19) fragment by infected monkeys, indicating that the antibodies were reactive with native MSP-1(19) antigen in vivo. The prepatent period and time to treatment was greatly delayed in the two monkeys that received Aotus immune serum, both of which developed a chronic intermittent low level infection. In vitro parasite growth inhibition assays (GIAs) confirmed the presence of inhibitory activity (40% maximum inhibition) in concentrated anti-MSP-1(19) immunoglobulin (4.8 mg/ml), but the peak concentrations we achieved in vivo (1 mg/ml) were not inhibitory in vitro. Subinhibitory levels of anti-MSP-1(19) antibodies achieved by passive transfer were not protective against P. falciparum challenge.

Animals↗

Percutaneous nephrostomy: placement under CT and fluoroscopy guidance.

OBJECTIVE: The purpose of this paper is to present our experience with CT- and fluoroscopy-guided percutaneous nephrostomy tube (PNT) placement and to describe the technique of placement with patients in the supine-oblique position. MATERIALS AND METHODS: A CT scanner was coupled with a ceiling-mounted C-arm for fluoroscopy at the CT table, PNT was done with CT localization and fluoroscopic control. We attempted 148 placements in 129 patients, with most patients in the supine or the supine-oblique position. RESULTS: Successful PNT placement was achieved in 144 (97%) of 148 kidneys. In the native kidney group, 101 (81%) of 124 PNTs were placed with the patients in the supine-oblique position. We experienced no major complications, three (2%) minor complications, and two (1%) catheter dislodgments. CONCLUSION: CT-fluoroscopy control allows routine PNT placement with patients in the supine or the supine-oblique position and is associated with the lowest complication rate to our knowledge.

Adolescent↗

Anterior approach to the cervicothoracic junction: an anatomic dissection.

The anterior surgical approach to the cervicothoracic spine presents a challenge to the spine surgeon. To adequately explore the anterior spine from C4 to T4 requires a midsternotomy with extended anterior cervical incision. This approach most adequately provides the extensive cranial-caudal exposure required in dealing with tumors at the cervicothoracic junction. Our surgical experience with five patients harboring tumors in this area of the spine has led us to reflect on the anatomy of the exposure and the corridors of approach at various levels of the cervicothoracic junction. Cadaver dissection and demonstration of the anatomic structures encountered in this exposure and the spinal subdivisions created by these various neurovascular structures will be presented. The anatomy, so demonstrated, will be correlated with the clinical cases.

Anatomy, Artistic↗

A solid-phase assay for the determination of protein tyrosine kinase activity of c-src using scintillating microtitration plates.

A solid-phase assay for the determination of protein tyrosine kinase (PTK) activity has been developed. The transfer of 33PO4 from ATP to the synthetic substrate poly(Glu, Tyr) 4:1 attached to the bioactive surface of scintillating microtiter plates served as the basis to evaluate enzyme activity. The procedure eliminates detection with phosphotyrosine antibodies, tedious separation of phosphorylated peptides with phosphocellulose membranes, and extensive washing steps. For these reasons, the traditionally time-consuming procedure can be performed with a simple three-step protocol. The method is highly accurate, rapid, and robotics friendly. The advantages over existing assays make this procedure especially suited for high throughput applications.

Animals↗

Safety, immunogenicity, and efficacy of Plasmodium falciparum repeatless circumsporozoite protein vaccine encapsulated in liposomes.

Seventeen malaria-naive volunteers received a recombinant Plasmodium falciparum vaccine (RLF) containing the carboxy- and the amino-terminal of the circumsporozoite protein (CSP) antigen without the central tetrapeptide repeats. The vaccine was formulated in liposomes with either a low or high dose of 3-deacylated monophosphoryl lipid A (MPL) and administered with alum by intramuscular injection. Both formulations were well tolerated and immunogenic. MPL increased sporozoite antibody titers measured by ELISA, Western blot, and immunofluorescence assay. One high-dose MPL vaccine formulation recipient developed a CSP-specific cytotoxic T lymphocyte response. After homologous sporozoite challenge, immunized volunteers developed patent malaria. There was no correlation between prepatent period and antibody titers to the amino- or carboxy-terminal. The absence of delay in patency argues against inclusion of the amino-terminal in future vaccines. A significant cytotoxic T lymphocyte response may have been suppressed by the inclusion of alum as an adjuvant.

Adolescent↗

Immunization of Aotus nancymai with recombinant C terminus of Plasmodium falciparum merozoite surface protein 1 in liposomes and alum adjuvant does not induce protection against a challenge infection.

Merozoite surface protein 1 (MSP-1) of Plasmodium falciparum is an antimalarial vaccine candidate. The highly conserved 19-kDa C-terminal processing fragment of MSP-1 (MSP-1(19)) is of particular interest since it contains epitopes recognized by monoclonal antibodies which inhibit the invasion of erythrocytes in vitro. The presence of naturally acquired anti-MSP-1(19) antibodies in individuals exposed to malaria has been correlated with reduced morbidity, and immunization with an equivalent recombinant P. yoelii antigen induces substantial protection against this parasite in mice. We have expressed P. falciparum MSP-1(19) in Escherichia coli as a correctly folded protein and immunized Aotus nancymai monkeys by using the protein incorporated into liposomes and adsorbed to alum. After vaccination, the sera from these animals contained anti-MSP-1(19) antibodies, some of which competed for binding to MSP-1(19) with monoclonal antibodies that inhibit parasite invasion of erythrocytes in vitro. However, after challenge with either a homologous or a heterologous strain of parasite, all animals became parasitemic and required treatment. The immunization did not induce protection in this animal model.

Adjuvants, Immunologic↗