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Biomedical subjects

B Chang

Publications and source records attributed to B Chang.

At least 127 records · Page 7Linked to original sources
PubMed1995

Mouse model for Usher syndrome: linkage mapping suggests homology to Usher type I reported at human chromosome 11p15.

Usher syndrome is a group of diseases with autosomal recessive inheritance, congenital hearing loss, and the development of retinitis pigmentosa, a progressive retinal degeneration characterized by night blindness and visual field loss over several decades. The causes of Usher syndrome are unknown and no animal models have been available for study. Four human gene sites have been reported, suggesting at least four separate forms of Usher syndrome. We report a mouse model of type I Usher syndrome, rd5, whose linkage on mouse chromosome 7 to Hbb and tub has homology to human Usher I reported on human chromosome 11p15. The electroretinogram in homozygous rd5/rd5 mouse is never normal with reduced amplitudes that extinguish by 6 months. Auditory-evoked response testing demonstrates increased hearing thresholds more than control at 3 weeks of about 30 decibels (dB) that worsen to about 45 dB by 6 months.

Animals↗
PubMed1995

Bclx regulates the survival of double-positive thymocytes.

The bclx gene has been shown to regulate programmed cell death in vitro. We now show that Bclx expression increases dramatically when T cells differentiate from CD4- CD8- (double negative) thymocytes to CD4+ CD8+ [double positive (DP)] thymocytes. In contrast single-positive (SP) thymocytes express negligible amounts of Bclx protein. This expression pattern contrasts with that of Bcl2, which is present in double-negative thymocytes, down-regulated in DP thymocytes, and reinduced upon maturation to SP thymocytes. Elimination of Bclx by gene targeting dramatically shortens the survival of DP thymocytes but not the survival of SP thymocytes or peripheral SP T cells. These data suggest that the induction of Bclx during thymic maturation plays a critical role in regulating the length of time DP thymocytes survive in the absence of selection.

Animals↗
PubMed1995

Phenylacetate synergizes with retinoic acid in inducing the differentiation of human neuroblastoma cells.

Phenylacetate, a natural metabolite of phenylalanine which was originally described as a plant growth hormone, has recently gained attention as a possible differentiation inducer for a variety of human tumor cell types. This interest prompted us to assess the ability of sodium phenylacetate (NaPA) to promote the differentiation of human neuroblastoma cells, both alone and in combination with retinoic acid (RA), a known inducer of neuroblastoma differentiation and maturation. Using the LA-N-5 cell line, we have determined that NaPA can stimulate the differentiation of neuroblastoma cells, as evidenced by dose-dependent inhibition of cell proliferation, neurite outgrowth, increased acetylcholinesterase activity and reduction of N-myc expression. Furthermore, NaPA and RA synergized in inducing differentiation, in that combination treatment resulted in cessation of cell growth along with morphologic and biochemical changes indicative of the loss of malignant properties. We have determined that NaPA can markedly enhance mRNA levels of the nuclear RA receptor-beta (RAR beta) in LA-N-5 cells prior to morphologic or other phenotypic changes induced by this compound. This effect appeared to be distinct from the ability of NaPA to alter tumor cell lipid metabolism via inhibition of protein isoprenylation. Thus among its varied effects on LA-N-5 cells, NaPA appears to interact with the RA pathway at the nuclear level by up-regulating RAR beta expression.

Cell Differentiation↗
PubMed1995

Prospective incidence of photic maculopathy after cataract surgery.

PURPOSE/METHODS: To determine the incidence of photic retinal injury during cataract surgery, we studied 37 consecutive patients with intravenous fluorescein angiography within ten days after cataract surgery. The microscope irradiance was standardized for all cases. RESULTS/CONCLUSIONS: Fluorescein evidence of photic retinal injury did not develop in any of the 37 cataract patients. Incidence rates for photic retinal injury induced by the surgical microscope vary considerably among ophthalmologists and most likely reflect differences in microscope brightness, surgical duration, and surgical technique.

Cataract Extraction↗
PubMed1995

Choroidal neovascularization in second eyes of patients with unilateral exudative age-related macular degeneration.

PURPOSE: To evaluate patients with unilateral occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) for the nature of the neovascularization which develops in the fellow eyes. METHODS: Patients with newly diagnosed unilateral occult CNV were followed prospectively for the development of CNV in the fellow eye. Patients were classified based on the type of occult CNV in the first eye: (1) those with associated serous pigment epithelial detachment (serous PED) and (2) those without. Demographic and clinical data, including the type of CNV in the second eyes, were compared. RESULTS: Choroidal neovascularization developed in 115 patients in the second eye. Fifty-six patients had occult CNV with a serous PED (also termed vascularized PED) in the first eye, and 59 patients had occult CNV without serous PED. The two groups did not differ significantly in the demographic and the clinical features evaluated. Well-delineated (or classic) CNV developed in the fellow eye of one patient in each group. Of the remaining 55 patients with vascularized PED in the first eye, the same type of occult CNV developed in 48 (87%) patients in the second eye. Of 58 (84%) patients in the second group, the same type of occult CNV developed in the second eye of 49 patients. This symmetric distribution of type of CNV between eyes is highly significant (P < 0.001). CONCLUSIONS: Eyes with occult CNV secondary to AMD can be classified by the presence or absence of an associated serous PED. Patients with unilateral occult CNV have a significant risk of occult CNV developing in the second eye, and the type of occult disease in the first eye is highly predictive of the type of neovascularized disease in the second eye. These findings are important with respect to natural history, and possibly to the treatment response and visual prognosis of patients with neovascularized AMD.

Aged↗
PubMed1995

Enhanced potency of 9-cis versus all-trans-retinoic acid to induce the differentiation of human neuroblastoma cells.

All-trans-retinoic acid (ATRA) has been shown to be one of the most potent chemical inducers of human neuroblastoma differentiation. The recent discovery that the stereoisomer of ATRA, 9-cis-retinoic acid (9-cis-RA), binds to both the retinoic acid and retinoid X series of receptors prompted us to evaluate the ability of this compound to promote differentiation of this cell type. Using the LA-N-5 cell line, we have now determined that 9-cis-RA can induce the differentiation of human neuroblastoma cells as evidenced by dose-dependent inhibition of cell proliferation, neurite outgrowth, increased acetylcholinesterase activity, and reduction of N-myc mRNA expression. In comparing the effects of 9-cis-RA to ATRA, we found that while both compounds induced qualitatively similar cholinergic (versus adrenergic) features in LA-N-5 cells, 9-cis-RA was 5-to-10-fold more potent than ATRA in its antiproliferative and differentiation activity. These results were supported by transient transfection experiments utilizing chloramphenicol acetyltransferase (CAT) plasmid constructs containing a retinoic acid responsive regulatory element which showed a 2-to-3-fold increase in reporter gene activity induced with 9-cis-RA over that seen with ATRA at pharmacologically relevant retinoid concentrations (> 10(-8) M). Furthermore, we have determined that 9-cis-RA can significantly enhance mRNA levels of the nuclear retinoic acid receptors alpha and beta in LA-N-5 cells. Taken together, these findings have established the ability of 9-cis-RA to induce neuroblastoma differentiation and suggest that this retinoic acid isomer may have better therapeutic characteristics than ATRA.

Acetylcholinesterase↗
PubMed1994

Preliminary crystallographic studies of four crystal forms of serum albumin.

Several crystal forms of serum albumin suitable for three-dimensional structure determination have been grown. These forms include crystals of recombinant and wild-type human serum albumin, baboon serum albumin, and canine serum albumin. The intrinsic limits of X-ray diffraction for these crystals are in the range 0.28-0.22 nm. Two of the crystal forms produced from human and canine albumin include incorporated long-chain fatty acids. Molecular replacement experiments have been successfully conducted on each crystal form using the previously determined atomic coordinates of human serum albumin illustrating the conserved tertiary structure.

Animals↗
PubMed1994

Biliary extracorporeal shock-wave lithotripsy: an update.

Since the mid-1980s, numerous clinical studies, involving hundreds of patients, have attested to the safety and efficacy of this technique. There have been no deaths, and occasional soft tissue damage appears to be temporary.

Bile Acids and Salts↗
PubMed1994

Retinoic acid up-regulates nuclear retinoic acid receptor-alpha expression in human neuroblastoma cells.

Retinoic acid (RA) nuclear receptors (RARs) are thought to mediate the cellular and molecular effects of RA on a wide variety of tissues. In most cell types, RAR alpha expression remains relatively constant following exposure to RA, while that of RAR beta is rapidly induced. In this study, we show that in human neuroblastoma, a cell type exceptionally sensitive to RA-induced differentiation, RAR alpha as well as RAR beta is markedly up-regulated by RA treatment. This effect was consistent in all 5 neuroblastoma cell lines tested and was reflected in a 2- to 5-fold increase in receptor mRNA levels as assessed by Northern-blot analysis. Using LA-N-5 human neuroblastoma cells, we found that receptor up-regulation occurred in a time- and dose-dependent fashion with increases in both RAR alpha and beta mRNA detectable 1-2 hr after the addition of RA. These inductions were not abrogated by cycloheximide, indicating that protein synthesis was not required for the RA responses. Nuclear run-off experiments combined with Northern-blot analysis of RAR alpha stability directly demonstrated that the up-regulation of RAR alpha mRNA levels reflected an increased rate of transcription without changes in message half-life. These findings, showing direct activation by RA of RAR alpha gene transcription in human neuroblastoma cells, suggest differences in the overall regulation of this receptor from that found in most other RA-inducible tissue.

Cell Differentiation↗
PubMed1994

The CDR1 sequences of a major proportion of human germline Ig VH genes are inherently susceptible to amino acid replacement.

The variable (V) genes of antigen-selected antibodies are known to exhibit a higher frequency of amino acid replacement mutations in the sequences encoding the antigen-contacting complementarity-determining regions (CDRs) than in those encoding the 'structural' framework regions (FRs). Here, Bernard Chang and Paolo Casali analyse the impact of regional differences in the codon composition of human germline Ig VH and VL genes on regional differences in the frequency of replacement mutations in the gene products (i.e. the antigen-binding sites of antibody molecules). This analysis reveals that CDR and FR sequences can differ significantly in their inherent susceptibility to amino acid replacement given any single nucleotide change. Thus, the CDR sequences of all the Ig VH genes analysed comprise a higher frequency of codons susceptible to replacement mutations than would be expected for a random sequence. Conversely, the FR sequences comprise codons less susceptible to replacement mutations than expected. Random accumulation of nucleotide changes throughout the coding sequence of an Ig V-gene segment containing CDRs inherently more prone to replacement mutations than the respective FRs would inevitably yield a higher rate of amino acid replacements in the CDRs than in the FRs. This would provide a fertile structural substrate of hypervariability for antigen selection while still maintaining the structural integrity of the FRs.

Amino Acid Sequence↗
PubMed1994

A coin in the airway.

A 69-year-old Chinese woman with widely metastatic endometrial carcinoma was found at autopsy to have a quarter in her air passages. Inquiry showed that her family had placed the coin in her mouth at the time of death according to traditional Chinese funeral practices. This practice is apparently not widely known among forensic pathologists.

Aged↗
PubMed1994

Elbow defect coverage with a one-staged, tunneled latissimus dorsi transposition flap.

Upper extremity reconstruction is very challenging due to the unavailability of expendable local muscles. A review of the literature reveals that the latissimus dorsi muscle has been used for functional restoration of elbow extension and flexion as well as soft-tissue coverage of upper arm and shoulder defects. In addition, the latissimus dorsi muscle has been used for forearm reconstruction. Although we have been unable to find any reports of the use of the latissimus dorsi muscle for pure coverage of complex elbow wounds, we have successfully used the latissimus dorsi transposition flap to cover complex elbow defects in a one-staged procedure for patients. In 3 of 4 patients, the latissimus dorsi transposition flap was the first choice. In the other patient, the latissimus dorsi flap was successfully used as an alternative choice for coverage of an open, comminuted elbow fracture after a failed rectus abdominis free tissue transfer. A technique is described for coverage of complex elbow defects by transferring a latissimus dorsi muscle on its vascular pedicle with or without an overlying skin island. This procedure is safe, one-staged, and results in minimal donor morbidity. The latissimus dorsi transposition flap provides reliable coverage of complex elbow defects and should be considered the flap of choice for coverage of the elbow.

Adult↗
PubMed1994

Effective coping with stroke disability in a community setting: the development of a causal model.

A proposed causal model based upon Lazarus' theory of psychological stress and coping was tested in a sample of 75 persons disabled by stroke. Coping constraints such as demographic and stroke factors were hypothesized to affect resources (perceived availability of social support, perceived effectiveness of social support, social contact), stress appraisal, coping behavior and coping effectiveness. Although the model did not fit the data, several path coefficients within the model were statistically significant. Functional status was positively related to resources and negatively related to the stressor. Resources were negatively related to the stressor and positively related to coping effectiveness. It was noted that the buffering effect of social support was related to the level of disability of the stroke person. Persons with functional disability following stroke also had decreased social contact, perceived less availability of social resources and increased threat to physical well-being, and had reduced coping effectiveness.

Activities of Daily Living↗