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Biomedical subjects

S Chan

Publications and source records attributed to S Chan.

At least 145 records · Page 8Linked to original sources
PubMed1996

In vivo muscle gene transfer of full-length dystrophin with an adenoviral vector that lacks all viral genes.

Duchenne muscular dystrophy (DMD) is an important target for gene transfer because of the disease's high frequency and devastating course. To date, adenoviral vector-mediated gene transfer for DMD has been unavailable because (1) adenoviral vectors were unable to accommodate the full-length dystrophin cDNA (14 kb); and (2) adenoviral vectors induced inflammatory reactions in the gene transfer recipient. We addressed both problems with a novel adenoviral vector that contains no viral genes and encodes 28.2 kb of foreign DNA including both the full-length dystrophin cDNA with the muscle creatine kinase promoter for transcriptional control and a lacZ marker gene. This report presents the in vivo expression of dystrophin and beta-galactosidase from this vector in skeletal muscle of the mdx mouse, a mutant mouse that lacks dystrophin. Somatic delivery of the vector by intramuscular injection in 6-day-old mice resulted in the expression of full-length, recombinant dystrophin at the muscle membrane. Dystrophin-associated proteins were restored in muscle fibers expressing recombinant dystrophin. Mdx muscle injected with our vector showed a decrease in the proportion of fibers with nuclei located centrally; centrally placed nuclei in muscle fibers are characteristic of cycles of degeneration and regeneration suffered by dystrophin-deficient muscle tissue. These results are strong evidence that adenoviral vector-mediated full-length dystrophin delivery provides substantial somatic function.

Adenoviridae↗
PubMed1996

Child psychiatric consultation and liaison in paediatrics.

Psychiatric problems are common in children with physical illness. The child psychiatrist can play a useful role in consultation, treatment and prevention of psychological problems in paediatrics. In addition, the child psychiatrist can contribute to staff support and education and research. Difficulties in liaison work are due mainly to differences in professional emphasis, deficits in communication and the stigma that is invariably linked to psychiatry.

Child↗
PubMed1996

Randomized trial of periportal peritoneal bupivacaine for pain relief after laparoscopic cholecystectomy.

The aim of this study was to determine whether injection of a long-acting local anaesthetic, in relation to the port sites at the level of the parietal peritoneum, would reduce postoperative pain following laparoscopic cholecystectomy. Patients were entered into a randomized, prospective, double-blind study comparing the effects of a standard technique, in which bupivacaine (total of 20 ml, 0.5 per cent) was injected into the subcutaneous periportal tissue around the four port sites, and a technique in which bupivacaine (total of 20 ml, 0.25 per cent) was injected into the subcutaneous periportal tissue as above with the addition of periportal parietal peritoneal injection of bupivacaine (total of 20 ml, 0.25 per cent). Two scores for pain, with the patient at rest, and on movement, were assessed 6 and 18 h after surgery using a visual analogue pain scale. Median pain score was significantly higher in patients who received standard technique (n = 40) than in those given peritoneal injection (n = 40) at both 6 (rest = 3.0 versus 1.0, movement = 5.0 versus 2.9) and 18 h (rest = 1.9 versus 0, movement = 3.2 versus 1.2). Both opiate and oral analgesic requirements were reduced in patients administered peritoneal injection, although this was not statistically significant. The addition of periportal injection of bupivacaine at the level of the parietal peritoneum, performed under direct vision, reduces pain after laparoscopic cholecystectomy.

Adult↗
PubMed1995

CD1-restricted CD4+ T cells in major histocompatibility complex class II-deficient mice.

Rather unexpectedly, major histocompatibility complex class II-deficient mice have a significant population of peripheral CD4+ T lymphocytes. We have investigated these cells at the population and clonal levels. CD4+ T lymphocytes from class II-deficient animals are thymically derived, appear early in ontogeny, exhibit the phenotype of resting memory cells, are potentially functional by several criteria, and have a diverse T cell receptor repertoire. They do not include substantially elevated numbers of NK1.1+ cells. Hybridomas derived after polyclonal stimulation of the CD4+ lymphocytes from class II-deficient animals include a subset with an unusual reactivity pattern, responding to splenocytes from many mouse strains including the strain of origin. Most members of this subset recognize the major histocompatibility complex class Ib molecule CD1; their heterogeneous reactivities and T cell receptor usage further suggest the involvement of peptides and/or highly variable posttranslational modifications.

Animals↗
PubMed1995

Developmental abnormalities and cortical sulcal enlargement in psychosis.

Neurodevelopmental abnormalities and cortical sulcal enlargement both occur in schizophrenia. To test the hypothesis that these abnormalities were related, CT scans from 164 psychotic patients (80 with schizophrenia) were reviewed. Neurodevelopmental abnormalities were observed in 11%. Abnormalities were equally prevalent in schizophrenia and other psychotic disorders. Cortical sulcal enlargement was observed in 39% of patients with schizophrenia, and was not associated with developmental abnormalities. Different mechanisms may contribute to distinct structural abnormalities.

Adolescent↗
PubMed1995

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Journal Article↗
PubMed1995

Open reduction and internal fixation for displaced intra-articular fractures of the os calcis.

Thirty-one patients with displaced intra-articular fracture of the os calcis who were admitted to Queen Mary Hospital, Hong Kong from 1989 to 1991 and who underwent open reduction and internal fixation and bone grafting of the os calcis, were followed up for at least 30 months. Pre- and postoperative X-rays were taken. Functional results were assessed clinically in terms of pain, deformities, activities and motion loss. The majority of the patients had acceptable functional outcome. The results were analysed in an attempt to correlate with the fracture pattern.

Accidents, Occupational↗
PubMed1995

Dissociation of mouse cardiac transplant rejection and donor alloantigen-specific T cell responsiveness.

Mouse hearts transplanted into MHC disparate donors are usually rejected 1 week after placement. It is widely accepted that alloantigen-reactive helper T lymphocytes (HTL) and cytotoxic T lymphocytes (CTL) are the key mediators of acute allograft rejection. This report demonstrates that the presence or absence of 'traditional' graft-reactive HTL and CTL is not necessarily related to allograft survival. In these studies, donor/recipient combinations disparate only at MHC or only at minor histocompatibility (mH) loci were employed. Allograft survival was monitored, donor-reactive IL-2 (interleukin-2) producing HTL and CTL were quantified by modified limiting dilution analysis, and serum levels of cytolytic alloantibody were determined. C57BL/10 hearts (H-2b) transplanted into B10.BR (H-2k) recipients (full MHC disparity) enjoyed prolonged survival despite massive infiltration of the allograft by donor-reactive HTL and CTL. IgM, but not IgG, donor-reactive alloantibody was present in the sera of these mice. Hence, traditional IL-2 producing HTL and CTL were not capable of mediating acute graft rejection, nor of providing help for alloantibody isotype switching in this MHC disparate combination. In contrast, C3H/HeN (H-2k) hearts transplanted into B10.BR (H-2k) recipients (mH disparity only) were acutely rejected. Donor-reactive HTL and CTL were rare or not detectable in these recipients, and cytolytic alloantibody was not detectable. Similar observations were made when B10.BR hearts were transplanted into C3H/HeN recipients. Interestingly, treatment of recipients with anti-CD4 monoclonal antibody prevented rejection of mH disparate allografts. Therefore, CD4+ T cells were required for rejection of mH disparate allografts, but this process was independent of detectable IL-2 production or CTL function. Hence, the significance of monitoring 'traditional' T cell functions should be questioned in certain donor/recipient combinations.

Animals↗
PubMed1995

Recombinant truncated dystrophin minigenes: construction, expression, and adenoviral delivery.

Duchenne muscular dystrophy (DMD) is a lethal genetic disorder for which there is currently no effective treatment. Although clinical application of adenoviral vector-mediated gene transfer has not been fully developed, it shows promise for the treatment of DMD. One significant problem posed by adenoviral vector-mediated gene transfer for DMD is that currently available adenoviral vectors cannot accommodate the entire 14-kb dystrophin cDNA. To address this problem, we selectively deleted regions of the murine dystrophin cDNA to produce truncated constructs. We created three constructs, each with an in-frame deletion of a segment (3.0, 4.4, and 5.7 kb) of the spectrin-like repeat region of dystrophin. As an additional modification, we removed the majority of the 3' untranslated region of the cDNA in expression vectors encoding some of these truncated constructs. Comparative quantitative expression studies after transfection into COS and C2C12 mouse muscle cells demonstrate variations in the level of expression with different deletions in the spectrin-like repeat region. Furthermore, deletion of the 3' untranslated region was tested for one recombinant construct and resulted in a reduction in the level of expression in both cell culture systems. Toward the ultimate goal of gene transfer therapy for DMD, we created an adenoviral vector from one of our truncated constructs. Using this vector, we demonstrated truncated dystrophin expression in vitro in primary mdx (dystrophin-deficient) muscle cells and in vivo in mdx mouse muscle. In vivo, recombinant dystrophin was properly localized to the muscle membrane.

Adenoviridae↗