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Biomedical subjects

Y T Chang

Publications and source records attributed to Y T Chang.

At least 19 recordsLinked to original sources
PubMed1996

Synthesis and iron binding studies of myo-inositol 1,2,3-trisphosphate and (+/-)-myo-inositol 1,2-bisphosphate, and iron binding studies of all myo-inositol tetrakisphosphates.

The first syntheses of the natural products myo-inositol 1,2,3-trisphosphate and (+/-)-myo-inositol 1,2-bisphosphate are described. The protected key intermediates 4,5,6-tri-O-benzoyl-myo-inositol and (+/-)-3,4,5,6-tetra-O-benzyl-myo-inositol were phosphorylated with dibenzyl N,N-di-isopropylphosphoramidite in the presence of 1H-tetrazole and subsequent oxidation of the phosphite. The crystal structures of the synthetic intermediates (+/-)-1-O-(tert-butyldiphenylsilyl)-2,3,O-cyclohexylidene-myo-inos itol and (+/-)-4,5,6-tri-O-benzoyl-1-O-(tert-butyldiphenylsilyl)-2,3-O-cycl ohexylidene- myo-inositol are reported. myo-Inositol 1,2,3-trisphosphate, (+/-)-myo-inositol 1,2-bisphosphate, and all isomeric myo-inositol tetrakisphosphates were evaluated for their ability to alter HO. production in the iron-catalysed Haber-Weiss reaction. The results demonstrated that a 1,2,3-grouping of phosphates in myo-inositol was necessary for inhibition, also that (+/-)-myo-inositol 1,2-bisphosphate potentiated HO. production. myo-Inositol 1,2,3-trisphosphate resembled myo-inositol hexakisphosphate (phytic acid) in its ability to act as a siderophore by promoting iron-uptake into Pseudomonas aeruginosa.

Binding Sites↗
PubMed1996

Alternative splicing in the coding region of human aromatic L-amino acid decarboxylase mRNA.

Total RNA from human neuroblastoma cells (SK-N-SH) was reverse transcribed and amplified using primers specific for aromatic L-amino acid decarboxylase (AADC). Two polymerase chain reaction (PCR) products were observed following agarose electrophoresis. Cycle sequencing of the PCR products revealed the larger fragment (414 bp) to be identical to the published human cDNA sequence (Type I). Sequencing of the smaller band (300 bp) demonstrated a form missing exon three (Type II). Both types of the mRNA were colocalized in human brain regions (gray matter and white matter) and other human tissues (liver, kidney, adipose, heart, adrenal gland and keratinocytes). The relative concentrations varied in each tissue studied but specific neuronal or non-neuronal patterns were not apparent. The study demonstrates alternative splicing within the coding region of the human AADC mRNA and the results suggest the possibility that two proteins are derived from the AADC gene in human tissues.

Aromatic-L-Amino-Acid Decarboxylases↗
PubMed1996

Construction and evaluation of a three-dimensional structure of cytochrome P450choP enzyme (CYP105C1).

The purpose of this work was to develop and carefully evaluate improved strategies for constructing reliable 3-D models of P450 isozymes. To this end, a unique combination of steps for building and evaluating a model structure was used to build a homology model of the P450choP isozyme, based on knowledge of the X-ray structures of P450cam, P450terp, P450BM-3 and P450eryF. Specifically, the reliability of this model was examined by systematic comparisons of its conformational, energetic, environmental and packing properties and those of the four reference proteins with corresponding properties from the database of proteins with known structures. The results showed that the examined properties of this model structure are well within the criteria established for reliable structures and are of nearly as good quality as those of the reference proteins. In addition, the result from a 120 ps unconstrained MD simulation of the model with structural waters provided evidence that the model is stable at room temperature. This 3-D model can now be reliably used for explicit characterization of substrate and inhibitor complexes. Most importantly, although it is envisioned that building models for mammalian P450s will be even more challenging, the steps described here should be very useful in future construction of 3-D models of mammalian P450 isozymes.

Amino Acid Sequence↗
PubMed1996

Extramammary Paget's disease: a report of 22 cases in Chinese males.

Extramammary Paget's disease (EMPD) is more frequently seen in Caucasian females than in males (3.2:1 female:male ratio). During the past 14 year period, we have collected 22 patients, all Chinese males, with EMPD. They presented with eczema-like lesions in the early stages in the genital or perianal regions. Histological sections showed Paget cells within the epidermis or skin appendages and even within the dermis. No underlying adnexal carcinoma or adjacent internal carcinoma could be detected after thorough examinations. Mode of therapy and outcome are presented. EMPD seems to affect more males than females in Orientals. The incidence of concomitant malignancy in Chinese male patients with genital Paget's disease seems to be much lower than that in Caucasians. However, if EMPD involves the glans penis or perianal area, a search for internal malignancy is still warranted.

Aged↗
PubMed1996

A new compound heterozygous frameshift mutation in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene causes salt-wasting 3 beta-HSD deficiency congenital adrenal hyperplasia.

We report a new compound heterozygous frameshift mutation in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene in a Pakistanian female child with the salt-wasting form of 3 beta-HSD deficiency congenital adrenal hyperplasia. The child, born with clitoral enlargement, manifesting salt-wasting adrenal crisis, and public hair growth during infancy, was treated with hormonal replacement therapy. The etiology of her congenital adrenal hyperplasia, however, was not defined. Two of her siblings, as well as one paternal cousin with ambiguous genitalia and palpable gonads and another paternal cousin with normal female genitalia, had symptoms of adrenal crisis and died during early infancy. Thus, although the family history suggested possible 3 beta-HSD deficiency disorder, suppressed adrenal function caused by excess glucocorticoid therapy in this child at 7 yr of age did not allow hormonal diagnosis. To confirm 3 beta-HSD deficiency, we sequenced the type II 3 beta-HSD gene in the patient, her family, and the parents of her decreased paternal cousins. The type II 3 beta-HSD gene region of a putative promoter, exons I, II, III, and IV, and exon-intron boundaries were amplified by PCR and sequenced in all subjects. The DNA sequence of the child revealed a single nucleotide deletion at codon 318 [ACA (Thr)-->AA] in exon IV in one allele, and two nucleotide deletions at codon 273 [AAA(Lys)-->A] in exon IV in the other allele. The remaining gene sequences were normal. The codon 318 mutation was found in one allele from the father, brother, and parents of the deceased paternal cousins. The codon 273 mutation was found in one allele of the mother and a sister. These findings confirmed inherited 3 beta-HSD deficiency in the child caused by the compound heterozygous type II 3 beta-HSD gene mutation. Both codon 273 and 318 mutations yielding frameshift and premature stop codons at codons 279 and 367, respectively, are predicted to result in an altered and truncated type II 3 beta-HSD protein, thereby causing salt-wasting 3 beta-HSD deficiency in the patient. The type II 3 beta-HSD gene findings and clinical history of her family members suggest that the patient's deceased siblings were likely affected males with the same compound heterozygous mutations of the gene as in the proband, whereas the deceased cousins were likely affected with the homozygous codon 318 mutation in the gene.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Bullous pemphigoid--a report of 86 cases from Taiwan.

We reviewed 86 cases of bullous pemphigoid and the results were compared with those reported in the literature. Seventy-eight per cent of the patients developed generalized blisters and 22% had localized blisters, including three cases of dyshidrosiform pemphigoid and one case of pretibial pemphigoid. Oral mucosal involvement was noticed in 12.8% of the patients. Fifteen per cent of the patients had internal malignancies but the incidence was not significantly different from the control group. Direct immunofluorescence in our series showed a high positive rate of 98.8%. Indirect immunofluorescence was positive in 48.1% of the 54 patients in whom this was carried out. Peripheral blood eosinophilia was observed in 22.1% of the patients. Prednisolone alone or in combination with immunosuppressive agents was the mainstay of treatment. Treatment side-effects was observed in 33% of the patients. Thirty per cent of the patients had a complete remission after a mean follow-up period of 26.9 months. Bullous pemphigoid (BP) is a chronic debilitating autoimmune blistering disease. It is characterized clinically by generalized tense bullae and histologically by subepidermal blisters. Immunofluorescence is crucial in the diagnosis and shows linear deposits of C3 and/or IgG at the basement membrane zone (BMZ). Information regarding this disease in Chinese patients is quite limited. In this study, 86 patients with BP were reviewed. The clinical and histological features, immunofluorescence, modes of therapy and outcome were studied.

Adolescent↗
PubMed1995

Specificity of the purified inositol (1,3,4,5) tetrakisphosphate-binding protein from porcine platelets.

The specificity of the inositol 1,3,4,5-tetrakisphosphate binding protein purified from porcine platelets [Cullen et al. (1995) Biochem. J. 305, 139-143] was examined using all the isomers of myo-inositol tetrakisphosphate. From the relative potencies of these compounds it appears that phosphorylation of the 1, 3 and 5 positions is essential for high affinity binding, that there is some tolerance of phosphorylation of the 6-hydroxyl, but none of a phosphate in the 2-position, and that phosphorylation of the 4-hydroxyl has very little influence. The binding of Ins(1,3,4,5)P4 was not appreciably altered by physiological Mg2+ concentrations, and the pH dependence of binding under physiological conditions showed a decline from pH 5.5 to pH 9.0.

Animals↗
PubMed1995

Penile basal cell carcinoma with eccrine differentiation.

Basal cell carcinoma (BCC) is rare on the penis. There have been only 17 cases of penile BCC reported in the literature. Eccrine differentiation may not be uncommon in BCC but has not been reported in penile BCC. We report here a 75-year-old man with multiple penile BCC with histological features of eccrine differentiation. A brief review of the literature is included. Basal cell carcinoma (BCC) is the most commonly diagnosed malignant skin tumour; it probably originates from pluripotential cells in the epidermis or hair follicle. More than 90% of BCCs are located on the head or neck, and its occurrence on the penis is rare. Seventeen cases of penile BCC have been reported in the literature.

Aged↗
PubMed1995

Absence of molecular defect in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene in premature pubarche children and hirsute female patients with moderately decreased adrenal 3 beta-HSD activity.

To date the molecular basis and hormonal criteria for inherited mild late-onset 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency congenital adrenal hyperplasia (CAH) have not been defined. We have thus investigated the presence or absence of mutation in the type II 3 beta-HSD gene encoding adrenal/gonadal 3 beta-HSD in each of five premature pubarche children and hirsute female patients manifesting moderately decreased adrenal 3 beta-HSD activity. ACTH-stimulated hormonal levels in all patients compared with mean levels in pubertal stage-matched normal subjects were between 2.5 and 6.5 SD for 17-hydroxypregnenolone levels, and between 2.5 and 7 SD for dehydroepiandrosterone levels in all except one patient. 17-Hydroxypregnenolone to cortisol ratios were between 2.5 and 4.3 SD, and dehydroepiandrosterone to androstenedione ratios were between 3 and 8.6 SD. The type II 3 beta-HSD gene regions of a putative promoter, exons I, II, III, and IV, and exon-intron boundaries in all subjects were amplified by polymerase chain reaction and then sequenced. All patients had normal sequences of the type II 3 beta-HSD gene in both alleles. Three female patients heterozygotic for severe 3 beta-HSD deficiency CAH with one allele mutation of the gene demonstrated normal ACTH-stimulated hormone profiles. These data indicate that moderately decreased adrenal 3 beta-HSD activity resulting in modestly increased delta 5 precursor steroid levels and delta 5 to delta 4 steroid ratios in premature pubarche and hirsute patients is not caused by a mutation in the type II 3 beta-HSD gene.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

[Swallowing of fixed denture following general anesthesia--a case report].

Dental injury is a common complication associated with endotracheal general anesthesia. According to a study in Japan, the incidence of dental injury caused by endotracheal intubation is 0.69%. In one study in our country, evaluation of the oral condition was performed before, during and after anesthesia, and the frequency of dental trauma is as high as 12.1%. Fragment(s) of tooth or denture may cause serious, or even fatal complications. We report a case of swallowing of fixed denture following endotracheal general anesthesia. Our accident involved a 33-yr-old male who had experienced bilateral auditory impairment as a result of chronic otitis media. The patient underwent right modified radical mastoidectomy under endotracheal general anesthesia. It might well be that the patient's maxillary fixed denture was loosened at the time of endotracheal intubation. However, patient's denture was normal in appearance and not much attention was paid to it. During his stay at the post-anesthesia care unit, he might have unconsciously swallowed his denture. Verification was later made by X-ray. On careful observation, his denture was found in the feces during defecation 30 h post-operatively.

Adult↗
PubMed1994

Enrichment of unlabelled human Langerhans cells by modified discontinuous Ficoll-metrizoate density medium and following Langerhans cell culture.

Highly enriched and specifically unlabelled human Langerhans cells (LC) from epidermal cell suspensions (ECS) are indispensable for the intensive study of LC function. Discontinuous Ficoll-metrizoate density gradient centrifugation was found to be a satisfactory method of enriching LC from ECS. In contrast to a previous study, however, the majority of LC floated on Ficoll-metrizoate with a density of 1.057 g/cm3 instead of 1.068 g/cm3. The concentration of unlabelled LC can be enriched to as high as 92% from the original 1.8-3.1% LC in ECS. Approximately 40-50% of original LC can be harvested. The procedure was also simplified by using a Schick razor instead of a dermatome to obtain thin epidermal sheets (about 0.25 mm in thickness), omitting the density gradients of 1.089 and 1.10 g/cm3 and using the avidin-biotin complex method to identify LC. LC are non-proliferative cells in in vitro culture systems. The viability of LC dropped to 20-30% after 3 days in the culture medium. It was also observed that LC tended to attach to aggregated keratinocytes in the culture system.

Cell Survival↗
PubMed1994

Primary cutaneous plasmacytomas.

Primary cutaneous plasmacytoma arising in the skin is very rare. The case of a young man suffering from primary cutaneous plasmacytomas, without an underlying disorder, is reported. The clinical, histopathological, electron microscopical and laboratory findings from the case are described.

Adult↗
PubMed1994

Synchronous bursting in a subset of interneurons inhibitory to the goldfish Mauthner cell: synaptic mediation and plasticity.

1. Presynaptic activity in the inhibitory network impinging on the Mauthner (M-) cell was investigated in the goldfish medulla in vivo using extra- and intracellular recordings. The inhibitory presynaptic volley elicited by stimulation of the contralateral vestibular nerve consisted of multiple successive peaks at high frequency (up to 1,000 Hz). Less pronounced multicomponent responses were recorded after antidromic activation of the M-cell. Such high-frequency "oscillatory" field potentials also occurred spontaneously. 2. In intracellular recordings, a subset of inhibitory interneurons showed evoked and spontaneous burst discharge. Burst action potentials were correlated with the peaks in the extracellular volley, suggesting that repetitive firing of these cells is synchronized. Nonbursting cells, on the other hand, fired single action potentials in response to vestibular stimuli and were not activated via the M-cell collateral network. 3. Bursting cells were determined morphologically to be part of the feedback inhibitory circuit. Their responses to stimulation of the contralateral vestibular nerve thus suggest the existence of a crossed excitatory pathway to these interneurons. 4. Vestibular-evoked excitatory postsynaptic potentials (EPSPs) in bursting interneurons had a short latency of 0.781 +/- 0.08 ms (mean +/- SD, n = 18) but reached threshold at 2.25 +/- 1 ms (n = 21). These characteristics are suggestive of a chemically mediated EPSP. Indeed, the evoked synchronous repetitive activity of these cells was prevented by superfusion with excitatory amino-acid receptor antagonists. 5. Bursting neurons showed several characteristics that differentiate them from nonbursting cells, including brief action potentials, plateau responses, and intense spontaneous subthreshold activity. 6. With extracellular recordings, tetanization of contralateral vestibular primary afferents evoked a long-lasting potentiation of oscillatory population responses in 11 of 27 cases. Furthermore in three experiments, the frequency of occurrence of spontaneous bursts was enhanced and a similar facilitation was detected at the intracellular level. 7. We conclude that a subset of interneurons in this inhibitory network is capable of repetitive discharges and that evoked as well as spontaneous firing in this population is synchronized. Although electrical coupling between interneurons may mediate synchronization and intrinsic membrane properties may promote burst activity, our data suggest strongly that repetitive firing requires chemically mediated transmission. Furthermore they indicate that the mechanisms underlying evoked as well as spontaneous bursting in this population show activity-dependent plasticity.

Animals↗
PubMed1994

Molecular basis of congenital adrenal hyperplasia in two siblings with classical nonsalt-losing 3 beta-hydroxysteroid dehydrogenase deficiency.

We report mutations of the type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) gene in two siblings, male and female, with congenital adrenal hyperplasia caused by classical nonsalt-losing 3 beta HSD deficiency. During childhood, the male sibling, born with ambiguous genitalia, and the female sibling, born with normal genitalia, both manifested symptoms of mild androgen excess; both apparently had normal zona glomerulosa function. Gonadal dynamic study at puberty showed the presence of partial gonadal 3 beta HSD deficiency in both siblings despite their spontaneous pubertal maturation. The 5'-region as well as exons I-II, III, and IV and portions of the adjacent introns of the type II 3 beta HSD gene were amplified by polymerase chain reaction and sequenced. In both siblings and their mother, an identical single nucleotide substitution mutation in intron III, six bases up-stream from exon IV, was identified in one allele. This mutation, G to A at nucleotide 6651, may create a new splicing junction and affect the normal splicing of the messenger ribonucleic acid. In the other allele of both siblings, a missense mutation from GGG (Gly) to AGG (Arg) at codon 129 (G129R) in exon IV was found. We assessed the effect of the G129R missense mutation on enzymatic activity by in vitro analysis of the mutant recombinant enzyme generated by site-directed mutagenesis after its transient expression in COS-1 cells. Using homogenates from transfected cells, the G129R 3 beta HSD enzyme showed a Km value for pregnenolone of 10 +/- 2 mumol/L compared with 1.00 +/- 0.03 mumol/L for the wild-type type II 3 beta HSD enzyme. When dehydroepiandrosterone was used as substrate, the Km value for G129R3 beta HSD was 14 +/- 2 mumol/L compared with 2.1 +/- 0.2 mumol/L for the wild-type II 3 beta HSD enzyme. In addition to an apparent decrease in affinity, the G129R mutation caused a marked decrease in the apparent relative specific activity, thus leading to apparent relative specific efficiencies (relative specific activity/Km) of 2.0% and 4.7% that of the normal type II 3 beta HSD using pregnenolone or dehydroepiandrosterone as substrate, respectively. It appears likely that this low level of activity is sufficient to prevent salt loss, but it is also possible that part of the enzymatic activity comes from the putative remaining percentage of correctly spliced n6651 allele in these patients.

3-Hydroxysteroid Dehydrogenases↗