Search PubMed⌕ Search

Biomedical subjects

T Chu

Publications and source records attributed to T Chu.

At least 37 records · Page 2Linked to original sources
PubMed1997

The Siemens virtual wedge.

A Siemens Virtual Wedge has recently been installed and commissioned at the Northeastern Ontario Regional Cancer Centre. Measurements reported below show that 1) Virtual Wedge factors are within 1.5% of 1; 2) percentage depth doses down to 15 cm for open and virtually wedged fields are identical to within 0.7%; 3) relative cross beam profiles for 60 degrees virtual and physical wedges are very similar except at the toe end where a 5% difference in relative dose has been observed and 4) the peripheral dose from the 60 degrees Virtual Wedge is about half of that from the 60 degrees physical wedge. A clinical protocol requiring combined open and 60 degrees wedged fields has been developed and validated. This protocol, which does not impair the utility of the Virtual Wedge, facilitates the use of on-line portal imaging and significantly reduces the effort required to commission the system.

Humans↗
PubMed1996

Disposition of methylenedioxymethamphetamine and three metabolites in the brains of different rat strains and their possible roles in acute serotonin depletion.

3,4-Methylenedioxymethamphetamine (MDMA) affects both dopamine and serotonin (5-HT) systems. One of its acute actions is to cause a reversible fall in steady-state brain 5-HT concentrations. To investigate the chemical basis of this acute effect, the brain levels of the parent compound and three major metabolites, 3,4- 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymethamphetamine (DHMA) and 6-hydroxy-3,4-methylenedioxymethamphetamine (6-OHMDMA), were monitored, together with 5-HT levels, over a period of 6 hr in male Sprague-Dawley (SD) rats. The temporal relationships between drug concentrations of both stereoisomers and depletions were evaluated first. There was no correlation between the concentrations of the compounds measured and the extent of 5-HT depletion. Brain levels of MDMA and MDA were higher than plasma levels and exhibited a stereoselectivity in that (-)-MDMA and (+)-MDA levels were higher than those of enantiomers. The relationship between the dose of ((+)-MDMA and reduction in 5-HT levels was next investigated in SD male, SD female, and Dark Agouti (DA) female rats. These animals exhibit different capabilities of MDMA metabolism. There is a lower level of MDA, the N-demethylated metabolite of MDMA, in female SD rats than in males. Female DA rats are deficient in CYP2D isozymes, one of the enzymes responsible for demethylenation of MDMA to DHMA at pharmacological concentrations of substrate. there was a significant accuulation of MDMA in the brain and plasma of DA rats, but their 5-HT depletion was somewhat attenuated. The results indicated that MDMA ++ was apparently not the single, causative agent for the acute 5-HT depletion, which may also involve a metabolite formed by CYP2D.

3,4-Methylenedioxyamphetamine↗
PubMed1996

Differential mRNA transport and the regulation of protein synthesis: selective sensitivity of Purkinje cell dendritic mRNAs to translational inhibition.

Although the majority of mRNAs expressed in neurons are confined to the perikaryon, a growing number appear to be transported into dendrites. It is likely that this allows for the local regulation of protein synthesis within discrete subcellular compartments. Here, three different subcellular distribution patterns are demonstrated for four mRNAs that encode proteins highly expressed in Purkinje cells and their dendrites; mRNAs are found in the perikaryon only, perikaryon and proximal dendrite, or perikaryon and proximal plus distal dendrites. Further, it is shown that transport of an mRNA into the dendrites increases its sensitivity to translational inhibition by diphtheria toxin. These data suggest a simple model whereby the transport machinery can regulate the translation of selected mRNAs. Thus, environmental signals that generally affect translational efficiency in concert with the selectivity provided by the transport machinery could provide a means to locally regulate the synthesis of a restricted pool of proteins.

Animals↗
PubMed1996

Mutations that perturb poly(A)-dependent maternal mRNA activation block the initiation of development.

Translational recruitment of maternal mRNAs is an essential process in early metazoan development. To identify genes required for this regulatory pathway, we have examined a collection of Drosophila female-sterile mutants for defects in translation of maternal mRNAs. This strategy has revealed that maternal-effect mutations in the cortex and grauzone genes impair translational activation and cytoplasmic polyadenylation of bicoid and Toll mRNAs. Cortex embryos contain a bicoid mRNA indistinguishable in amount, localization, and structure from that in wild-type embryos. However, the bicoid mRNA in cortex embryos contains a shorter than normal polyadenosine (poly(A)) tail. Injection of polyadenylated bicoid mRNA into cortex embryos allows translation demonstrating that insufficient polyadenylation prevents endogenous bicoid mRNA translation. In contrast nanos mRNA, which is activated by a poly(A)-independent mechanism, is translated in cortex embryos, indicating that the block in maternal mRNA activation is specific to a class of mRNAs. Cortex embryos are fertilized, but arrest at the onset of embryogenesis. Characterization of grauzone mutations indicates that the phenotype of these embryos is similar to cortex. These results identify a fundamental pathway that serves a vital role in the initiation of development.

Animals↗
PubMed1996

Refractive changes in chicks with form-deprivation myopia.

PURPOSE: To study the refractive changes of form deprivation of myopia. METHODS: Haisaik chickens were used to establish the animal models of myopia. Monocular eyelids were sutured for form deprivation on the 5th day after chickens birth. The chickens were examined by optometer and the anteroposterior axis, transverse and vertical diameters were measured by verniermicrometer. RESULTS: Form deprivation leads to myopic refractive abnormality (P < 0.001). The ocular anteroposterior axis (P < 0.005), transverse and vertical diameters lengthen (P < 0.05). CONCLUSION: Form deprivation is the main cause of the development of myopia.

Animals↗
PubMed1995

Characterization of proteins in detergent-resistant membrane complexes from Madin-Darby canine kidney epithelial cells.

We previously isolated detergent-resistant membrane complexes (DRMs) that were not solubilized after extraction of Madin-Darby canine kidney cells with Triton X-100 on ice. The complexes were rich in glycosphingolipids, cholesterol, and glycosylphosphatidylinositol (GPI)-anchored proteins. In this study, we examined the protein composition of DRMs and further characterized the detergent solubility of these structures. Eight to ten cell-surface proteins, including proteins from both apical and basolateral membranes, were recovered in DRMs. Most DRM proteins, however, were not exposed to the surface of whole cells, and we did not detect the complex of cell-surface proteins described by Sargiacomo et al. in a similar study [Sargiacomo, M., et al. (1993) J. Cell Biol. 122, 789-807]. Almost all proteins in DRMs were solubilized by Triton X-100 at temperatures above 30 degrees C or by octyl glucoside on ice. In contrast, a GPI-anchored protein, placental alkaline phosphatase, was mostly solubilized by Triton X-100 after extraction at 10 degrees C. This protein was insoluble in ice-cold Triton X-100 when first delivered to the plasma membrane and remained so for at least 6 h after synthesis. A fraction of the lipids in DRMs remained insoluble after extraction with Triton X-100 at 37 degrees C. DRM lipids were not solubilized by octyl glucoside, suggesting that this detergent selectively extracts proteins from DRMs.

Animals↗
PubMed1995

Local control of granule cell generation by cerebellar Purkinje cells.

Cerebellar Purkinje cells were ablated by the specific expression of diphtheria toxin in these cells in transgenic mice. Purkinje cell degeneration during early postnatal development shows a zonally restricted pattern which has been exploited in order to look for local secondary effects. The most obvious early effect is the alignment of gaps in the Purkinje cell layer with dramatically thinned zones in the overlying EGL, the germinal layer from which granule cells are generated. Within these EGL zones in the transgenic mutant, markers that distinguish matrix from mantle cells demonstrate a preferential loss of the proliferative cells. Comparison of BrdU incorporation in the mutant vs wild-type confirms the reduction in proliferation. In the mutant, in situ labeling of DNA fragmentation associated with apoptotic cell death shows abundant labeling of granule cells that have exited the EGL, but not of progenitor cells in the EGL. Thus, although a trophic role for Purkinje cells has been well documented, these observations further suggest a mitogenic role which can be exerted locally.

Animals↗
PubMed1994

Specific A+T-rich repetitive DNA sequences in maxicircles from wildtype Leishmania mexicana amazonensis and variants with DNA amplification.

To explain the low cross-hybridization between kinetoplast DNA maxicircles of Leishmania parasites that show DNA amplification and those of parasites without DNA amplification, we isolated and cloned two maxicircle fragments, one specific to each group of parasites. The cloned fragment from wildtype L. m. amazonensis (MbpW94) and that from an arsenite-resistant variant with DNA amplification (MpbA29) hybridized only to maxicircles from parasites of the group from which the fragment was originally derived. Both fragments were A+T-rich, tandemly repeated, and lacked long conserved open reading frames and transcriptional products. MpbW94 (685 bp) was harbored in a segment of roughly 12 kb in maxicircles of wildtype parasites and of an arsenite-resistant variant without DNA amplification, while MbpA29 (1121 bp) occupied a 6- to 7-kb segment of maxicircle DNA in arsenite- and tunicamycin-resistant variants with DNA amplification. These maxicircle DNA segments appear to resemble previously described maxicircle divergent regions of other kinetoplastids. The presence of these specific sequences allows differentiation between maxicircles of drug-resistant L. m. amazonensis with DNA amplification and those of parasites without DNA amplification and helps explain the low cross-hybridization between maxicircles of the two parasite groups. Furthermore, these sequences allow the study of the kinetics of the changeover of A+T-rich regions of maxicircles during the transition period from one maxicircle type to the other.

Animals↗
PubMed1994

The normal Langerhans cell and the LCH cell.

The epidermal Langerhans cell is the bone marrow-derived dendritic, antigen-presenting cell of the skin. It is characterised by a unique intracytoplasmic organelle--the Birbeck granule--and constitutively expresses class II MHC molecules and the CD1a glycoprotein. The Langerhans cell represents one of the most potent antigen-presenting cells of the body, and fulfils an important role in detecting foreign antigen entering the body through the skin and in immune surveillance. The distribution of Langerhans cells is restricted to the skin, lymph nodes, bronchial mucosa and thymus. The discovery by Nézelof in 1973 that the lesional cells in the disease then called 'Histiocytosis X' contained Birbeck granules established the close relationship between the Langerhans cell and this disease and led ultimately to the adoption of the name Langerhans cell histiocytosis to replace the older term. The LCH cell expresses the phenotype of a Langerhans cell apparently 'fixed' at an early stage of cell activation. The LCH cell is, however, functionally defective in antigen presentation, and the tissue distribution of the disease--affecting bone, skin, lymph node, lung, liver, spleen, CNS, gastro-intestinal tract and bone marrow--is quite different from the normal distribution of the Langerhans cell. Studies are now under way throughout the world to investigate the relationship between the normal Langerhans cell and the LCH cell. Specifically we need to identify whether the LCH cell is a cell arrested at a specific time in normal Langerhans cell ontogeny or if it represents a response to a biological insult to the mature Langerhans cell or its precursors.

Antigen-Presenting Cells↗
PubMed1992

Purification of functional active epidermal Langerhans cells: a simple and efficient new technique.

Our knowledge of the functional activity of the epidermal Langerhans cell has been severely hampered by the lack of an easy method of purification of these cells that is both efficient and reproducible. In the present study we have used immunomagnetic beads directly conjugated to an IgM class mouse anti-human human leukocyte antigen DR monoclonal antibody to positively select human Langerhans cells from an epidermal cell suspension. Cells were then treated with a high-affinity polyclonal anti-mouse immunoglobulin that detached the beads by competing with the antigen for the antigen-binding site on the monoclonal antibody. This procedure allowed removal of the immunomagnetic beads, leaving Langerhans cells free from bound antibody. Recovery of Langerhans cells ranged from 40 to 80% of the starting number of Langerhans cells. The resulting cells were up to 99% CD1a positive and showed potent functional activity in the allogeneic mixed epidermal cell - lymphocyte reaction. Keratinocytes were shown to exert a profound inhibitory effect on Langerhans cell function that could not be prevented by indomethacin. This method is technically simple and allows good recovery of a highly purified population of Langerhans cells that are functionally active.

Cell Separation↗
PubMed1989

Pseudofolliculitis barbae.

Pseudofolliculitis and acne keloidales are common skin conditions which are difficult to control and may cause considerable problems for the patient, resulting in disfiguring scarring. In a limited open study, 1% clindamycin was found to be a simple and effective treatment for both conditions.

Acne Keloid↗
PubMed1988

The incidence of immunosuppression-related skin disease in long-term transplant patients.

One hundred and twenty-one patients who had received a renal allograft between 4 months and 21 years previously (mean +/- SD, 71 +/- 62 months) were studied. Seventy-two patients were conventionally immunosuppressed with azathioprine and prednisolone, and 36 had been exposed to the current regime of cyclosporine, azathioprine, and prednisolone. Forty-five patients had viral warts, of whom 20 had more than 10 warts. The presence of viral warts was significantly associated with pale skin type, excess sun exposure, and with duration of allograft. Viral warts were significantly more common in those on conventional immunosuppressive therapy, but this could be solely a reflection of the difference in duration of transplant between the 2 groups. Twelve patients were found to have developed dysplastic or neoplastic skin lesions since transplantation. The incidence of dysplasia increased with increasing age and was significantly associated with pale skin type, excess sun exposure, and duration of allograft. Despite the shorter duration of treatment in those on the new treatment regime, there was no difference between the 2 groups in the proportion of patients with dysplastic skin lesions. Immunosuppression-related skin disease may be a significant problem in allograft recipients in this country, and we suspect that patients taking cyclosporine will have similar problems to those on conventional immunosuppressive drugs alone. Immunosuppressed patients should be advised to avoid sun exposure, to use sunscreens, and should be monitored carefully for the development of dysplastic lesions.

Dermatomycoses↗
PubMed1988

Double-blind comparison of terfenadine, chlorpheniramine, and placebo in the treatment of chronic idiopathic urticaria.

The efficacy of terfenadine, a nonsedating H1 antihistamine, in the management of chronic idiopathic urticaria was compared with chlorpheniramine and placebo in a parallel multicenter trial. Subjects with symptoms of hives for 3 days per week for at least 6 weeks were initially screened and admitted if no identifiable cause for symptoms could be determined. Patients entered a single-blind placebo period, and if hives of moderate severity were present for at least 3 days during the week, they were randomly assigned in a double-blind fashion to take terfenadine, 60 mg twice daily, chlorpheniramine, 4 mg three times a day, or placebo for 6 weeks. Data were analyzed for 122 patients. Those patients receiving both active treatments noted significant improvement in symptoms: pruritus, redness, number of hives, and waking hours during which hives were present, at the end of the first day of therapy. Symptom control by terfenadine was statistically superior to placebo during all 6 weeks, as rated by both patients and investigators. However, statistical significance was not achieved for chlorpheniramine at all observation points. Diphenhydramine was permitted as a relief medication for refractory symptoms and was taken by 52% of subjects receiving placebo, 26% taking chlorpheniramine, and only 9% of patients who were receiving terfenadine. In addition to providing superior symptom control, terfenadine caused less drowsiness and fatigue than chlorpheniramine. Terfenadine is a useful therapeutic agent for primary management of chronic idiopathic urticaria.

Adolescent↗
PubMed1987

The repair of psoralen monoadducts by the Escherichia coli UvrABC endonuclease.

We have examined the interactions of UvrABC endonuclease with DNA containing the monoadducts of 8-methoxypsoralen (8-MOP) and 4,5',8-trimethylpsoralen (TMP). The UvrA and UvrB proteins were found to form a stable complex on DNA that contains the psoralen monoadducts. Subsequent binding of UvrC protein to this complex activates the UvrABC endonuclease activity. As in the case of incision at pyrimidine dimers, a stable protein-DNA complex was observed after the incision events. For both 8-MOP and TMP, the UvrABC endonuclease incised the monoadduct-containing strand of DNA on the two sides of the monoadduct with 12 bases included between the two cuts. One incision was at the 8th phosphodiester bond on the 5' side of the modified base. The other incision was at the 5th phosphodiester bond 3' to the modified base. The UvrABC endonuclease incision data revealed that the reactivity of psoralens is 5'TpA greater than 5'ApT greater than 5'TpG.

Bacterial Proteins↗