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Biomedical subjects

B Chang

Publications and source records attributed to B Chang.

At least 73 records · Page 4Linked to original sources
PubMed1999

Immunohistochemical localization of types 1 and 2 5alpha-reductase in human scalp.

The predominant form of 5alpha-reductase (5aR) in human scalp is 5aR1. None the less, clinical studies have shown that finasteride, a selective inhibitor of 5aR2, decreases scalp dihydrotestosterone and promotes hair growth in men with androgenetic alopecia. Immunolocalization studies were thus carried out to examine 5aR isozyme distribution within scalp and, in particular, to determine whether 5aR2 might be associated with hair follicles. 5aR2 was localized using both a rabbit polyclonal and a mouse monoclonal antibody. 5aR1 was detected with a mouse monoclonal antibody. The specificity of these reagents was demonstrated both by immunofluorescence and Western blot analyses of COS cells overexpressing human 5aR1 or 5aR2. When cryosections of scalp from men with androgenetic alopecia were stained with antibody against 5aR2, using immunoperoxidase avidin-biotin complex methodology, immunostaining was observed in the inner layer of the outer root sheath and, in more proximal regions of the follicle, in the inner root sheath. Staining was also prominent in the infundibular region of the follicle, with less intense staining extending throughout the granular layer of the epidermis. Some staining was also seen in sebaceous ducts. Similar results were obtained with both the polyclonal and monoclonal 5aR2 antibodies. In contrast, in scalp cryosections stained with antibody to 5aR1, no immunostaining was observed within hair follicles. Intense staining for the type 1 isozyme was, however, detected within sebaceous glands. Our immunolocalization data suggest that the results seen in clinical trials of men with male pattern hair loss treated with finasteride may be due, at least in part, to local inhibition of 5aR2 within the hair follicle.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Single-strand conformational polymorphism (SSCP)-detected p53 gene mutations are a less sensitive marker of malignancy in pleural fluids than p53 immunostaining.

p53 immunostaining has been advocated as a marker of malignancy in pleural biopsies and serous fluids. The object of this study was to compare the sensitivity and specificity of p53 immunostaining for the detection of malignant cells in pleural fluids with a technique designed to detect p53 gene mutations in exons 5, 6, 7 and 8 by SSCP and nucleotide sequencing. Five out of eight pleural fluids containing adenocarcinoma showed p53 immunostaining and two of these also showed polymorphisms on SSCP and a mutation on sequencing. None of the 10 benign pleural fluids showed immunostaining for p53 or polymorphisms on SSCP. We believe that the poor sensitivity of p53 gene mutation by SSCP is mainly due to DNA from the background reactive cells 'swamping' the mutant DNA. We do not advocate its use as a diagnostic aid.

Adenocarcinoma↗
PubMed1999

Renal renin-angiotensin system dysregulation caused by partial bladder outlet obstruction in fetal sheep.

BACKGROUND: To determine whether fetal renal obstruction activates the renal renin-angiotensin system (RAS), an important mediator in normal kidney development and obstructive nephropathy, we used a model of fetal partial bladder outlet obstruction (PBOO). METHODS: Total RNA and protein was extracted from kidney of sheep fetuses with partial bladder outlet obstruction created at 95 days gestation, after 2 (N = 6) and 5 weeks of obstruction (term; N = 6), and from normal fetal sheep at various time points between 60 and 135 days of gestation (total N = 19). Relative levels of mRNA for renin, angiotensinogen, type 1 and 2 angiotensin II (Ang II) receptors (AT-1 and AT-2), and transforming growth factor-beta1 (TGF-beta1) were assessed by semiquantitative reverse transcription-polymerase chain reaction. Expression levels of AT-2 receptor protein were measured by Western blot analysis. RESULTS: Renin mRNA expression was increased (250%) after two weeks of obstruction. In normal fetuses, AT-1 expression was low at 60 to 75 days of gestation and increased toward the end of gestation, whereas AT-2 expression showed a reversed pattern. At 109 days, PBOO caused an increased expression of AT-2 mRNA compared with normals (400%). Correspondingly, AT-2 receptor protein was more abundant in obstructed kidneys. TGF-beta1 mRNA expression was significantly increased in obstructed kidneys at 109 days gestation. CONCLUSIONS: These observations confirm the reciprocal developmental regulation of AT-1 and AT-2 receptors' expression, suggesting their functional role in renal development. Partial bladder outlet obstruction produces specific alterations: increased renin expression and altered balance of receptor subtypes, which may induce altered functional and vascular regulation of the obstructed fetal kidney. TGF-beta1, a mediator of Ang II-induced fibrosis, may play a role in inducing and propagating interstitial fibrosis.

Animals↗
PubMed1999

Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1.

The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism essential for embryonic development in mammals. Mutations in the human JAGGED1 ( JAG1 ) gene, which encodes a ligand for the Notch family of transmembrane receptors, cause the autosomal dominant disorder Alagille syndrome. We have examined the in vivo role of the mouse Jag1 gene by creating a null allele through gene targeting. Mice homozygous for the Jag1 mutation die from hemorrhage early during embryogenesis, exhibiting defects in remodeling of the embryonic and yolk sac vasculature. We mapped the Jag1 gene to mouse chromosome 2, in the vicinity of the Coloboma ( Cm ) deletion. Molecular and complementation analyses revealed that the Jag1 gene is functionally deleted in the Cm mutant allele. Mice heterozygous for the Jag1 null allele exhibit an eye dysmorphology similar to that of Cm /+ heterozygotes, but do not exhibit other phenotypes characteristic of Cm /+ mice or of humans with Alagille syndrome. These results establish the phenotype of Cm /+ mice as a contiguous gene deletion syndrome and demonstrate that Jag1 is essential for remodeling of the embryonic vasculature.

Animals↗
PubMed1999

Closure of chronic abdominal wall defects: a long-term evaluation of the components separation method.

Incisional hernias and abdominal wall defects are frequently iatrogenic problems that have been found to complicate as many as 11% of all abdominal operations. Current techniques for closure of large, chronic abdominal wall defects have limitations. The use of local musculofascial flaps rather than fascial patches (i.e., the tensor fascia lata) or synthetic material for the repair of chronic abdominal wall defects is preferable. The superiority of innervated muscle flaps that provide dynamic abdominal support has been demonstrated. This report focuses on patients with chronic abdominal wall defects in whom previous techniques have failed. An algorithmic approach to planned reconstruction is presented utilizing the "components separation" technique as its foundation. Thirty-seven patients who underwent abdominal reconstruction following this algorithm are reviewed and their clinical course is outlined. The components separation technique provides a compound innervated and vascularized muscle flap for dynamic support of the reconstructed abdominal wall. The experience documented here and by others suggests that this technique is a safe and effective method for reconstructing the abdominal wall in patients with recurrent herniation. Enterocutaneous fistulas, however, continue to present a challenge to the surgeon.

Abdominal Muscles↗
PubMed1999

Salvage of free flaps after secondary venous ischemia by local delivery of heparin.

Recent studies have demonstrated that heparin may protect against reperfusion injury through a direct effect on the microvascular endothelium that is independent of its effect on systemic coagulation. The purpose of this study was to determine whether local delivery of low-dose heparin has a role in the salvage of musculocutaneous flaps after secondary venous ischemia and revascularization. Cutaneous maximus musculocutaneous flaps were transplanted to the contralateral groin in adult Sprague-Dawley rats. All flaps were subjected to 2 hours of primary arteriovenous ischemia followed by 20 hours of reperfusion. The flaps were then subjected to a 6-hour secondary venous ischemic insult followed by anastomotic revision and reperfusion. Animals in group I received no adjunctive treatment. Those in group II were treated with low-dose heparin (5-6 U per kilogram per hour) infused systemically via the inferior epigastric vein. Those in group III received the same dose of heparin infused locally into the flap via the inferior epigastric artery. The dose of heparin used in groups II and III was insufficient to prolong the activated partial thromboplastin time above normal values. At 7 days, mean flap necrosis was 60.8% in group I and 62.1 in group II. Local heparin delivery (group III) resulted in complete survival of all flaps. Histological examination after 48 hours of reperfusion demonstrated improved microvascular patency and reduced neutrophilic infiltration in the flaps of group III animals. Thus, local infusion of low-dose heparin resulted in significantly improved flap salvage through a mechanism independent of its effect on systemic coagulation.

Animals↗
PubMed1999

Grouping of 20 reference strains of Legionella species by the growth ability within mouse and guinea pig macrophages.

20 Reference strains of Legionella species, isolated from human, were classified according to their ability to grow within thioglycolate-induced peritoneal macrophages of mice and guinea pigs. Inbred and congenic mice were used to study the effect of the natural resistance genes Lgn1 and Bcg that are expressed phenotypically in the mouse macrophages. The Lgn1 gene controlled the intracellular growth of Legionella pneumophila Philadelphia-1 and Legionella jordanis GIFU 12657, but the Bcg gene did not affect the intracellular growth of any organism examined. Based on these results and the growth ability in guinea pig macrophages, the 20 reference strains were divided into four groups. This grouping will help us to understand a variety of modes of interaction between Legionella species and macrophages.

Animals↗
PubMed1999

Microsatellite abnormalities in plasma of patients with breast carcinoma: concordance with the primary tumour.

AIMS: To detect microsatellite abnormalities in the primary tumours and plasma of patients with breast carcinoma. METHODS: Plasma was obtained from 17 breast carcinoma patients before surgery. Corresponding tumour and benign lymph node (control) samples for each of the carcinoma patients were obtained from paraffin blocks. DNA was extracted from the plasma samples and the paraffin embedded tissue using previously described methods. RESULTS: The 17 primary tumours showed two examples of loss of heterozygosity and three examples of microsatellite instability; the 17 plasma samples showed three and one, respectively. Many of the longer microsatellites (over 200 base pairs) were difficult to amplify from plasma. The investigations suggested that this was because of the highly fragmented nature of plasma DNA. Only one example of loss of heterozygosity and one example of microsatellite instability showed a concordant pattern in both primary tumour and plasma. These were both in the same patient. CONCLUSIONS: DNA mutations concordant with those in the primary carcinomas can occasionally be detected in the plasma of patients with breast carcinoma. However, the frequency would have to be markedly improved before this could be of any diagnostic value.

Biomarkers, Tumor↗
PubMed1999

Intronic enhancers control expression of zebrafish sonic hedgehog in floor plate and notochord.

The signalling molecule Sonic hedgehog (Shh) controls a wide range of differentiation processes during vertebrate development. Numerous studies have suggested that the absolute levels as well as correct spatial and temporal expression of shh are critical for its function. To investigate the regulation of shh expression, we have studied the mechanism controlling its spatial expression in the zebrafish. We employed an enhancer screening strategy in zebrafish embryos based on co-injection of putative enhancer sequences with a reporter construct and analysis of mosaic expression in accumulated expression maps. Enhancers were identified in intron 1 and 2 that mediate floor plate and notochord expression. These enhancers also drive notochord and floor plate expression in the mouse embryo strongly suggesting that the mechanisms controlling shh expression in the midline are conserved between zebrafish and mouse. Functional analysis in the zebrafish embryo revealed that the intronic enhancers have a complex organisation. Two activator regions, ar-A and ar-C, were identified in intron 1 and 2, respectively, which mediate mostly notochord and floor plate expression. In contrast, another activating region, ar-B, in intron 1 drives expression in the floor plate. Deletion fine mapping of ar-C delineated three regions of 40 bp to be essential for activity. These regions do not contain binding sites for HNF3beta, the winged helix transcription factor previously implicated in the regulation of shh expression, indicating the presence of novel regulatory mechanisms. A T-box transcription factor-binding site was found in a functionally important region that forms specific complexes with protein extracts from wild-type but not from notochord-deficient mutant embryos.

Animals↗
PubMed1999

Severe ocular abnormalities in C57BL/6 but not in 129/Sv p53-deficient mice.

PURPOSE: To demonstrate the importance of genetic background interaction on the development of ocular phenotypes in p53-deficient mice. METHODS: Eyes of adult mice, homozygous and heterozygous for the p53 gene disruption in the 129/SvJ and C57BL/6J (B6) genetic backgrounds, and their F1 progeny were examined by indirect ophthalmoscopy and by light microscopy. RESULTS: Indirect ophthalmoscopy revealed unilateral or bilateral vitreal opacities, fibrous retrolental tissue, and retinal folds in adult B6 mice but not in 129/Sv mice homozygous for a p53 null mutation. In B6 p53-/- mice, blood vessels extended from the peripapillary inner retina through the posterior vitreous and into the retrolental membrane. Optic nerves were hypoplastic. CONCLUSIONS: These findings indicate that alleles from the B6 background contribute to the aberrant ocular phenotypes observed in p53 deficiency. They also suggest that p53 or the pathway in which it functions may be important for normal eye development.

Abnormalities, Multiple↗
PubMed1999

Clinical analysis of 69 patients with familial benign chronic pemphigus.

OBJECTIVE: To analyze the clinical feature, efficacy of treatment and prognosis in familial benign chronic pemphigus (FBCP). METHODS: Sixty-nine cases of FBCP were retrospectively analyzed. RESULTS: The ratio of male to female is 3.93:1 in 69 patients (55 males, 14 females). The mean age at the onset was 29.09 years (3-60 years). There was familial history in 27 families in all of the cases. The lesion usually involved in genital area, neck, axillae and popliteal fossa. Erythemas and vesicles on the soles were seen only in 1 case. Histopathologically 44 cases had special features of FBCP, and immunopathologically 8 cases were direct immunofluorescence (DIF) negative, in which one case had C3 linear deposition along dermoepidermal junction. The combined regimen was more effective. The low-dose X-ray could improve the effect. CONCLUSION: The disease is transmitted as an irregular autosomal dominant trait. The condition in males is more frequent than that in females, probably owing to the different level of female hormone in both sexes. Our patients have the same clinical features as those reported in the literature, but the erythema, vesicle lesions on sole have not been documented in the literature. The combined therapy should be adopted in this condition.

Adult↗
PubMed1999

[Determination and analysis of physical factors affecting insulin fluorescent spectrum].

Insulin is an important factor which regulates cell metabolism and growth. The influences on insulin fluorescent spectrum by pulse electrical field, concentration and temperature were determined in this paper. It was proved that pulse electrical field, concentration and temperature could influence insulin fluorescent spectrum, and thus influence insulin confirmation and insulin biological activity. The mechanism of insulin influenced by pulse electrical field is different to temperature. It is possible that the electrical field influences the insulin fluorescent spectrum by changing Tyr position and the temperature influences the insulin fluorescent spectrum by molecule thermal motion. The insulin confirmation influenced by electrical field is steady.

Fluorescence↗
PubMed1998

Characterization of the mouse Prox1 gene.

Prox1, a vertebrate homologue of Drosophila prospero, encodes a divergent homeodomain protein. We have isolated and characterized full length mouse Prox1 cDNA and genomic clones. Mouse Prox1 gene mapped to position 106.3 cM from the centromere of Chromosome 1, which is very close to the retinal degeneration mutation, rd3. Although the coding sequence and exon-intron junctions of the Prox1 genes of wild type and rd3 mutant mice are identical, Northern blot analysis indicated that the ratio of the short (2.3 kb) and long (8 kb) forms of Prox1 mRNA is different in RNA isolated from wild type and rd3 retinas. Immunostaining of the eyes from wild type and rd3 animals also revealed differences in the distribution of Prox1 protein in the retina and lens. These data suggest that the rd3 mutation affects expression of the mouse Prox1 gene.

Amino Acid Sequence↗
PubMed1998

Characterization of the mouse Myoc/Tigr gene.

Mutations in the myocilin (MYOC), also known as Trabecular meshwork-Inducible Glucocorticoid Response (TIGR) gene can lead to juvenile open-angle glaucoma in human and may be responsible for at least 3% of primary open-angle glaucoma. To develop a mouse model of primary open angle glaucoma, and to get deeper insight into the mechanisms of the MYOC/TIGR gene regulation and function, we have isolated and characterized full size mouse Myoc/Tigr cDNA and genomic clones. The mouse and human MYOC/TIGR genes have the same exon-intron structure and contain 3 exons, although the mouse gene is 6 kb shorter than the human gene (10 kb versus 16 kb) due to differences in the length of introns. The MYOC/TIGR gene encodes a moderately conserved protein, which is 82% identical between human and mouse. The encoded protein is 14 amino acids shorter at the N-terminus in the mouse than in the human (490 versus 504 amino acids). Mouse and human MYOC/TIGR genes show a similar pattern of expression in adult ocular and nonocular tissues. The mouse Myoc/Tigr gene was mapped to Chromosome 1 at position 82.8 cM from the centromere. All residues, which were identified in the human MYOC/TIGR protein as critical for glaucoma development, are conserved in the mouse Myoc/Tigr.

Adult↗
PubMed1998

Transcriptional upregulation of retinoic acid receptor beta (RAR beta) expression by phenylacetate in human neuroblastoma cells.

Sodium phenylacetate (NaPA) has been shown to synergize with retinoic acid (RA) in inducing the differentiation of human neuroblastoma cells. Our studies indicated that NaPA can impact on the RA differentiation program by upregulating nuclear retinoic acid receptor-beta (RAR beta) expression. We have found that NaPA does not alter the half-life of RAR beta mRNA; thus, increased stability of mRNA levels does not contribute to NaPA induction. In contrast, NaPA was able to specifically activate a reporter gene construct (delta SV beta RE-CAT) which contains a retinoic acid response element (RARE beta) that is located in the RAR beta promoter. Activation of delta SV beta RE-CAT by NaPA also occurred in neuroblastoma cells cotransfected with a nuclear retinoic acid receptor expression vector, demonstrating the independence of this activation on cellular RAR levels. Taken together, our findings suggest that induction of RAR beta by NaPA is regulated at the level of transcription and mediated through the retinoic acid response element, RARE beta. This effect may account, at least in part, for the strong synergy between NaPA and RA in promoting neuroblastoma differentiation.

Antimetabolites, Antineoplastic↗