Search PubMed⌕ Search

Biomedical subjects

K S Lau

Publications and source records attributed to K S Lau.

At least 37 records · Page 2Linked to original sources
PubMed1998

Gamma-interferon activates a nuclear protein that binds to the gamma-interferon activation site of the thyroglobulin gene.

The release of interferon-gamma (IFNgamma) has been demonstrated from the infiltrating T lymphocytes of the thyroid gland from patients with autoimmune thyroid disease (AITD). We have shown previously that IFNgamma inhibited thyroglobulin (Tg) gene transcription, and that its action was mediated by an increase in intracellular calcium and inositol phosphates. In the present study, we tried to determine the specific site of action of IFNgamma on the Tg gene. A 565 bp fragment (position -530 to +34) spanning the transcriptional start site of the human Tg promoter was ligated to the luciferase plasmid and transiently transfected into human thyrocytes. Stimulation with TSH (10 mIU/l) and IFNgamma (500 IU/l) resulted in a twofold increase and a 60% reduction in the luciferase activity respectively, similar to the effect observed with the endogenous Tg gene. Deletion studies revealed that the region with the strongest suppression by IFNgamma lay between 5' -388 to -258. Mobility gel shift experiments and DNA footprinting experiments demonstrated that the action of IFNgamma was mediated through a trans-acting protein which complexed to position -282 to -262 TTGAGCCTGTTCCCTC CAAA. Position -272 to -261 TTCCCTCCAA corresponded to the gamma-interferon activation site (GAS) consensus sequence TTNC(C)T NNNA. The turnover time of the nuclear protein lasted for only 4 h although the suppressive effect of IFNgamma on Tg gene transcription lasted for 48 h. The effect of IFNgamma was lost when the thyrocytes were co-treated with genistein, a specific tyrosine kinase inhibitor. The presence of the GAS in the promoter sequence of the Tg gene confirms the specific action of IFNgamma in thyroid hormone metabolism. In conclusion, apart from its regulatory role in T cell development and perpetuation of the immune response in AITD, IFNgamma may also play a role in altering cellular function of the thyrocytes by its action on the Tg gene promoter.

Base Sequence↗
PubMed1998

Bilevel positive airway pressure nasal mask ventilation in patients with acute hypercapnic respiratory failure.

The efficacy and complications of bilevel positive airway pressure nasal mask ventilation for 22 patients with acute hypercapnic respiratory failure were reviewed retrospectively. The median patient age was 73 years (range, 57-92 years). The most common primary diagnosis (77%) was chronic obstructive pulmonary disease. The median duration of ventilation was 72.0 hours (range, 0.9 hours to 35 days). Within a median of 12 hours (range, 1-24 hours) after the initiation of therapy, there were significant improvements in the arterial oxygen and carbon dioxide tensions, oxygenation ratio, and arterial-alveolar ratio. Fourteen patients (64%) were treated successfully. Success with therapy was associated with a lower Acute Physiology and Chronic Health Evaluation score, a higher arterial oxygen tension, higher oxygenation and arterial-alveolar ratios, and lower respiratory and pulse rates. Complications were uncommon. We conclude that bilevel positive airway pressure nasal mask ventilation can be useful for patients with acute hypercapnic respiratory failure but who are otherwise clinically stable.

Journal Article↗
PubMed1997

nNOS and Ca2+ influx in rat pancreatic acinar and submandibular salivary gland cells.

Regulation of agonist-activated Ca2+ influx by the NOS pathway through generation of cGMP is being found in an increasing number of cell types. In the present work, we examined the role of the NOS pathway in agonist-evoked [Ca2+]i oscillations and attempted to identify the NOS isoform most likely to regulate Ca2+ influx. For this, we first show that two Ca(2+)-mobilizing agonists acting on pancreatic acinar cells, bombesin (BS) and the cholecystokinin analog CCK-JMV-180 (CCKJ), evokes different type of [Ca2+]i oscillations. The BS-evoked [Ca2+]i oscillations rapidly became acutely dependent on the presence of extracellular Ca2+, whereas the CCKJ-evoked oscillations continue for long periods of time in the absence of Ca2+ influx. This differential behavior allowed us to isolate Ca2+ influx and study its regulation while controlling for non specific effects on all other Ca2+ transporting events involved in generating [Ca2+]i oscillations. Inhibitors of selective steps in the NOS pathway inhibited agonist-induced cGMP production. The inhibitors were then used to show that scavenging NO with reduced hemoglobin, inhibition of guanylyl cyclase with 1H-[1,2,4] oxadiazolo[4,3-a] quinoxaline-1-one (ODQ) and inhibition of protein kinase G with Rp-8-pCPT-cGMPS inhibited [Ca2+]i oscillations evoked by BS but not those evoked by CCKJ. These findings were extended to duct and acinar cells of the SMG. In these cells, Ca(2+)-mobilizing agonists stimulate large Ca2+ influx, which was inhibited by all inhibitors of the NOS pathway. Western blot analysis and immunolocalization revealed that the cells did not express iNOS, eNOS was expressed only in blood vessels and capillaries whereas nNOS was expressed at high levels next to the plasma membrane of all cells. Accordingly, the nNOS inhibitor 7-nitroindazole (7-NI) inhibited BS- but not CCKJ-evoked [Ca2+]i oscillations and Ca2+ influx into SMG acinar and duct cells. Thus, together, our findings favor nNOS as the isoform activated by the Ca2+ released from internal stores to generate cGMP and regulate Ca2+ influx.

Animals↗
PubMed1996

Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy.

Neuronal nitric oxide synthase (nNOS) in fast-twitch skeletal muscle fibers is primarily particulate in contrast to its greater solubility in brain. Immunohistochemistry shows nNOS localized to the sarcolemma, with enrichment at force transmitting sites, the myotendinous junctions, and costameres. Because this distribution is similar to dystrophin, we determined if nNOS expression was affected by the loss of dystrophin. Significant nNOS immunoreactivity and enzyme activity was absent in skeletal muscle tissues from patients with Duchenne muscular dystrophy. Similarly, in dystrophin-deficient skeletal muscles from mdx mice both soluble and particulate nNOS was greatly reduced compared with C57 control mice. nNOS mRNA was also reduced in mdx muscle in contrast to mRNA levels for a dystrophin binding protein, alpha 1-syntrophin. nNOS levels increased dramatically from 2 to 52 weeks of age in C57 skeletal muscle, which may indicate a physiological role for NO in aging-related processes. Biochemical purification readily dissociates nNOS from the dystrophin-glycoprotein complex. Thus, nNOS is not an integral component of the dystrophin-glycoprotein complex and is not simply another dystrophin-associated protein since the expression of both nNOS mRNA and protein is affected by dystrophin expression.

Animals↗
PubMed1996

Oxygen upregulates nitric oxide synthase gene expression in ovine fetal pulmonary artery endothelial cells.

Nitric oxide (NO) is critically involved in oxygen-mediated pulmonary vasodilatation in the fetus and newborn. We determined the effects of prolonged alterations in oxygenation on endothelial NO synthase (eNOS) gene expression in early passage ovine fetal intrapulmonary artery endothelial cells (PAEC). PAEC were exposed to PO2 = 50 or 150 mmHg for 48 h, and eNOS protein expression was evaluated by immunoblot analysis. eNOS protein expression was 2.7-fold greater at higher oxygen tension; eNOS upregulation was also evident after 24 h. Inducible NOS protein was not detectable by immunoblot at either level of oxygenation. In the lung, the effect of oxygen on eNOS expression may be specific to the endothelium, as eNOS expression in bronchiolar epithelial cells of Clara cell lineage was not altered by varying oxygen tension. The oxygen-related increase in eNOS protein in the fetal PAEC was associated with 2.5-fold greater NOS enzymatic activity. In parallel, there was a 2.8-fold rise in eNOS mRNA abundance. Thus eNOS gene expression in ovine fetal PAEC is upregulated by oxygen, and this is mediated at the level of gene transcription or mRNA stability. This process may play an important role in oxygen modulation of pulmonary vasomotor tone in the fetus and newborn.

Animals↗
PubMed1995

Differential regulation of Ca2+ release-activated Ca2+ influx by heterotrimeric G proteins.

The least understood aspect of the agonist-induced Ca2+ signal is the activation and regulation of the Ca2+ release-activated Ca2+ influx (CRAC) across the plasma membrane. To explore the possible role of heterotrimeric G proteins in the various regulatory mechanisms of CRAC, continuous renal epithelial cell lines stably expressing alpha 13 and the constitutively active alpha qQ209L were isolated and used to measure CRAC activity by the Mn2+ quench technique. Release of intracellular Ca2+ by agonist stimulation or thapsigargin was required for activation of CRAC in all cells. Although the size of the internal stores was similar in all cells, CRAC was 2-3-fold higher in alpha 13- and alpha qQ209L-expressing cells. However, the channel was differentially regulated in the two cell types. Incubation at low [Ca2+]i, inhibition of the NOS pathway, or inhibition of tyrosine kinase inhibited CRAC activity in alpha 13 but not alpha qQ209L cells. Treatment with okadaic acid prevented inhibition of the channel by low [Ca2+]i and the protein kinase inhibitors in alpha 13 cells. These results suggest that expression of alpha qQ209L dominantly activates CRAC by stabilizing a phosphorylated state, whereas expression of alpha 13 makes CRAC activation completely dependent on phosphorylation by several kinases. G proteins may also modulate CRAC activity independently of the phosphorylation/dephosphorylation state of the pathway to increase maximal CRAC activity. Furthermore, our results suggest a general mechanism for regulation of CRAC that depends on coupling of receptors to specific G proteins.

Animals↗
PubMed1995

Expression and characterization of branched-chain alpha-ketoacid dehydrogenase kinase from the rat. Is it a histidine-protein kinase?

The recombinant rat branched-chain alpha-ketoacid dehydrogenase kinase has been amplified from rat kidney cDNA, based on the previously reported rat cDNA sequence (Popov, K. M., Zhao, Y., Shimomura, Y., Kuntz, M. J., and Harris, R. A. (1992) J. Biol. Chem. 267, 13127-13130). This kinase was expressed in Escherichia coli as a fusion protein with bacterial maltose-binding protein (MBP). Expression was improved by overexpression of chaperonins GroEL and GroES. The MBP-kinase, when reconstituted with lipoylated recombinant E2 (dihydrolipoyl transacylase), catalyzed phosphorylation of recombinant E1 (branched-chain alpha-ketoacid decarboxylase) with a kcat of 28.5 nmol of phosphate/min/nmol of MBP-kinase at 25 degrees C. Recombinant MBP-kinase alone demonstrated a slow rate of autophosphorylation with a kcat of 3.25 pmol of phosphate/min/nmol of kinase at 25 degrees C. Serine 22 of the kinase was identified as the possible site of autophosphorylation by Edman microsequencing analysis. Autophosphorylated kinase cannot transfer phosphate to E1, indicating that autophosphorylation of kinase is not an intermediate in ATP-dependent phosphorylation of E1. Therefore, despite the reported sequence similarity to prokaryotic histidine protein kinases, the mitochondrial rat branched-chain alpha-ketoacid dehydrogenase kinase apparently does not phosphorylate E1 via a histidine-mediated phosphotransfer reaction. Significant corrections to the published cDNA sequence of rat branched-chain alpha-ketoacid dehydrogenase kinase are included.

ATP-Binding Cassette Transporters↗
PubMed1995

TNF-alpha and IFN-gamma induce expression of nitric oxide synthase in cultured rat medullary interstitial cells.

Cytokines increase the expression of the inducible (type II) nitric oxide synthase (NOS) in macrophages, liver, and renal epithelial cells. Previously, we found that cultured rat medullary interstitial cells (RMIC) contain high levels of soluble guanylyl cyclase. To determine whether these cells can also produce NO, we studied the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on NO production, NOS II mRNA, and NOS II protein expression. Both TNF-alpha and IFN-gamma, in the presence of a low concentration of the other cytokine, caused dose-dependent increases in NO production. Exposure to TNF-alpha and IFN-gamma stimulated the production of NOS II mRNA, as determined by Northern blotting. Restriction mapping of reverse transcription-polymerase chain reaction products indicated that normal cells contained macrophage NOS II, whereas cytokine-stimulated cells contained primarily vascular smooth muscle NOS II and some macrophage NOS II. The appearance of NOS II protein was demonstrated by Western blotting. RMIC cell guanosine 3',5'-cyclic monophosphate accumulation increased 129-fold in response to the cytokines. NOS inhibitors decreased nitrite production. We conclude that 1) TNF-alpha and IFN-gamma induce the expression of vascular smooth muscle NOS II and production of NO in RMIC, and 2) NO acts as an autocrine activator of the soluble guanylyl cyclase in RMIC.

Amino Acid Oxidoreductases↗
PubMed1995

Interferon-gamma increases intracellular calcium and inositol phosphates in primary human thyroid cell culture.

Interferon-gamma (IFN gamma) is believed to play a role in the pathogenesis of autoimmune thyroid disease, as it is known to exert diverse effects on thyroid metabolism. These include induction of human leukocyte antigen class II expression, inhibition of gene expression of thyroglobulin and thyroid peroxidase, as well as inhibition of cellular proliferation. However, the mechanism of action of IFN gamma in thyrocytes has not been clearly defined. We studied the action of IFN gamma on the production of inositol phosphates and intracellular Ca2+ mobilization in primary cultures of human thyrocytes using the fluorescent Ca2+ indicator fura-2. IFN gamma increased the production of inositol mono-, bis-, and trisphosphates and caused a dose-dependent increase in intracellular Ca2+ ([Ca2+]i) at 37 C. Preincubation with 12-O-tetradecanoylphorbol-13-acetate, which activates protein kinase C, resulted in the abolition of the IFN gamma response, suggesting that protein kinase C was involved in a negative feedback loop resulting in inhibition of IFN gamma-induced [Ca2+]i rise. Prior release of intracellularly stored Ca2+ with thapsigargin, the microsomal Ca2+ pump inhibitor, also abolished the response of IFN gamma. Mobilization of [Ca2+]i resulted in Ca2+ entry across the plasma membrane, which could be blocked by La3+, the inorganic Ca2+ antagonist. The tyrosine protein kinase inhibitor, genistein, inhibited the production of inositol phosphates and the elevation of [Ca2+]i induced by IFN gamma, but had no effect on ATP, suggesting that tyrosine protein kinase is involved in the signaling transduction of IFN gamma. We conclude that the mobilization of intracellular Ca2+ and the production of inositol phosphates are two important signaling events for the action of IFN gamma in human thyrocytes.

Alkaloids↗
PubMed1994

Endothelial nitric oxide synthase is expressed in cultured human bronchiolar epithelium.

Nitric oxide (NO) is an important mediator of physiologic and inflammatory processes in the lung. To better understand the role of NO in the airway, we examined constitutive NO synthase (NOS) gene expression and function in NCI-H441 human bronchiolar epithelial cells, which are believed to be of Clara cell lineage. NOS activity was detected by [3H]arginine to [3H]citrulline conversion (1,070 +/- 260 fmol/mg protein per minute); enzyme activity was inhibited 91% by EGTA, consistent with the expression of a calcium-dependent NOS isoform. Immunoblot analyses with antisera directed against neuronal, inducible, or endothelial NOS revealed expression solely of endothelial NOS protein. Immunocytochemistry for endothelial NOS revealed staining predominantly in the cell periphery, consistent with the association of this isoform with the cellular membrane. To definitively identify the NOS isoform expressed in H441 cells, NOS cDNA was obtained by degenerate PCR. Sequencing of the H441 NOS cDNA revealed 100% identity with human endothelial NOS at the amino acid level. Furthermore, the H441 NOS cDNA hybridized to a single 4.7-kb mRNA species in poly(A)+ RNA isolated from H441 cells, from rat, sheep, and pig lung, and from ovine endothelial cells, coinciding with the predicted size of 4.7 kb for endothelial NOS mRNA. Guanylyl cyclase activity in H441 cells, assessed by measuring cGMP accumulation, rose 6.6- and 5.4-fold with calcium-mediated activation of NOS by thapsigargin and A23187, respectively. These findings indicate that endothelial NOS is expressed in select bronchiolar epithelial cells, where it may have autocrine effects through activation of guanylyl cyclase. Based on these observations and the previous identification of endothelial NOS in a kidney epithelial cell line, it is postulated that endothelial NOS may be expressed in unique subsets of epithelial cells in a variety of organs, serving to modulate ion flux and/or secretory function.

Amino Acid Oxidoreductases↗
PubMed1993

Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: multiple-exon skipping as a secondary effect of the mutations.

We have identified two novel mutant alleles in the transacylase (E2) gene of the human branched-chain alpha-keto acid dehydrogenase (BCKAD) complex in 6 of 38 patients with maple syrup urine disease (MSUD). One mutation, a 2-bp (AT) deletion in exon 2 of the E2 gene, causes a frameshift downstream of residue (-26) in the mitochondrial targeting presequence. The second mutation, a G-to-T transversion in exon 6 of the E2 gene, produces a premature stop codon at Glu-163 (E163*). Transfection of constructs harboring the E163* mutation into an E2-deficient MSUD cell line produced a truncated E2 subunit. However, this mutant E2 chain is unable to assemble into a 24-mer cubic structure and is degraded in the cell. The 2-bp (AT) deletion and the E163* mutant alleles occur in either the homozygous or compound-heterozygous state in the 6 of 38 unrelated MSUD patients studied. Moreover, an array of precise single- and multiple-exon deletions were observed in many amplified E2 mutant cDNAs. The latter results appear to represent secondary effects on RNA processing that are associated with the MSUD mutations at the E2 locus.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1992

Structure of the gene encoding dihydrolipoyl transacylase (E2) component of human branched chain alpha-keto acid dehydrogenase complex and characterization of an E2 pseudogene.

We have determined the structural organization of the dihydrolipoyl transacylase (E2) gene of the human branched chain alpha-keto acid dehydrogenase complex. The single copy E2 gene spans approximately 68 kilobases of genomic DNA. The complete coding region consisting of the 5'- and 3'-untranslated regions, the mitochondrial targeting sequence (61 amino acids), and the mature E2 sequence (421 amino acids) are encoded by 11 exons ranging from 62 to 2239 base pairs. All the donor and acceptor splice sites conform to the gt-ag rule. Sequence analysis of the promoter-regulatory region showed the presence of a "CAAT box"-like sequence 537 bases upstream of the transcription initiation site. The "TATA box"-like sequence is absent. Also located in this region are sequences resembling glucocorticoid-responsive and cAMP-responsive elements, fat-specific elements, and Sp1- and AP-2-binding sites. Several sets of direct and inverted repeats are also present. Promoter assays using human hepatoma cells (Hep-G2) and Swiss mouse preadipocytes (3T3-L1) showed that a 4.1-kilobase PstI fragment upstream of the transcription start site confers high expression of the luciferase reporter gene. Moreover, an intronless E2 pseudogene was isolated. It corresponds to the complete mitochondrial presequence and the lipoyl-bearing domain that are encoded by exons I through IV of the functional E2 gene. However, the E2 pseudogene contains multiple base changes, deletions, and insertions, and is flanked by short direct repeats. The data indicate that the E2 pseudogene is a retroposon.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1992

The complete cDNA sequence for dihydrolipoyl transacylase (E2) of human branched-chain alpha-keto acid dehydrogenase complex.

We have determined the complete nucleotide sequence for the cDNA encoding human dihydrolipoyl transacylase (E2) using the rapid amplification of cDNA ends (RACE) procedure. The full-length E2 cDNA is 3535 nucleotides in length. The coding region spans 1446 bp and the 3'-noncoding region spans 2074 bp. The latter contains three Alu repetitive sequences and two transcription termination sites.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1992

Incidence of ras oncogene activation in lung carcinomas in Hong Kong.

BACKGROUND: In Hong Kong, lung carcinomas contribute to the majority of cancer deaths among Chinese. Point mutational activation of ras oncogenes has been observed in several populations. The incidence of these mutations in Hong Kong lung carcinomas was investigated. METHODS: Lung resections obtained from 52 Chinese patients whose conditions were newly diagnosed as non-small cell lung cancer, paraffin sections from 29 Chinese patients with previously diagnosed adenocarcinoma of the lung, and paraffin sections from 49 squamous cell carcinomas were examined for the presence of point mutations in Ki-ras codon 12, N-ras codon 61, and Ha-ras codon 12 oncogenes by allele-specific hybridization after specific amplification of appropriate regions of the DNA using the polymerase chain reaction. RESULTS: Among the 130 lung carcinomas investigated, Ki-ras point mutations were detected in seven cases, of which six were adenocarcinomas and one a squamous cell carcinoma. No mutations were detected in the N-ras and Ha-ras codons. CONCLUSIONS: The incidence of Ki-ras codon 12 point mutational activation in Chinese patients with adenocarcinomas was 6 of 63 (9.5%). The incidence of Ki-ras 12 point mutational activation among men with lung adenocarcinomas in Hong Kong (6 of 32 patients, 18.8%) is significantly different from that in women in Hong Kong (0 of 31 patients, 0%). Although ras oncogenes are implicated as having a role in the development of lung adenocarcinomas, especially among smokers, it is clear from these data that they are not associated with the unusually high incidence of lung adenocarcinomas among women in Hong Kong.

Adenocarcinoma↗
PubMed1992

Assessment of an EIA for measuring human serum erythropoietin as compared with RIA and an in-vitro bioassay.

A recently developed enzyme-linked immunosorbent assay (EIAZ, ELISA) using two murine monoclonal anti-erythropoietin antibodies was compared with a radioimmunoassay (RIA) and a commercial in-vitro bioassay, EPOS, for measuring serum erythropoietin (Epo) in humans. Specificity and validity for Epo-EIA and the other two assays were examined. The serum Epo in normal subjects was 18 +/- 12 mU/ml (mean +/- SD, n = 80) for EIA compared with 22.5 +/- 18.5 mU/ml (n = 20) for RIA and 136 +/- 132 mU/ml (n = 14) for the bioassay. The serum Epo concentrations in normals and patients were highly comparable between EIA and RIA for Epo (P less than 0.01, r = 0.95). Epo concentrations by the EIA for normal female and male subjects were 20.5 +/- 13 and 16.5 +/- 10 mU/ml, respectively. Epo levels in patients with secondary polycythaemia or autoimmune haemolytic anaemia were significantly higher than normal subjects by the three methods. Epo levels in patients with chronic renal failure were within the normal range. By the EPOS bioassay, the Epo concentrations of normals and patients with renal failure were significantly higher than expected (136 +/- 132 and 447 +/- 273, respectively). Due to its inherent design, the EPOS bioassay possibly measures bone marrow proliferative activity in response to other serum growth regulators besides erythropoietin and was found to be unsuitable for clinical assessment of Epo. We concluded that the new EIA and RIA were similarly sensitive, reliable and accurate for measurement of serum Epo. The EIA method has the advantage of being less time consuming, more convenient and avoids the use of a radioisotope.

Adolescent↗
PubMed1992

The role of interferon-gamma in lymphocytic thyroiditis: its functional and pathological effect on human thyrocytes in culture.

Interferon-gamma (IFN-gamma) has been recognized to possess diverse non-immunological effects on epithelial cells such as cellular growth and differentiation. We have previously demonstrated that IFN-gamma suppressed thyroid-stimulating hormone (TSH)-stimulated thyroglobulin (TG) synthesis in human thyrocytes through inhibition of TG gene transcription. To define the pathological mechanism involved in the action of IFN-gamma, we studied the ultrastructural changes of human thyrocytes cultured in monolayer. Stimulation of the thyrocytes with TSH 10 mU/ml for 2 days resulted in marked increase in TG release into the medium. This was accompanied by elongation of microvilli, increase in follicles and acinar formation, increase in secretory granules and prominence of Golgi apparatus and rough-surfaced endoplasmic reticulum. Addition of IFN-gamma (500 U/ml) resulted in marked degeneration with shrinkage of the cell membrane, vacuolation of cytoplasm, swollen mitochondria and presence of lysosomal granules. Co-culturing the thyrocytes with the IFN-gamma and TSH resulted in suppression of the morphological responsiveness to TSH. There was also suppression of TSH-induced TG secretion. However, at 500 U/ml IFN-gamma did not cause lysis of the thyrocytes as estimated by the cellular DNA content. Furthermore, binucleated cells were frequently encountered in those wells that were treated with IFN-gamma for either 2 or 5 days. The findings suggest that IFN-gamma resulted in de-differentiation and degeneration of the thyrocytes, which subsequently regained the growth potential and showed attempts at regeneration. This may explain why most patients with lymphocytic thyroiditis recover from the acute injury and do not suffer from permanent hypothyroidism.

Cells, Cultured↗
PubMed1991

Premature termination of transcription and alternative splicing in the human transacylase (E2) gene of the branched-chain alpha-ketoacid dehydrogenase complex.

We have isolated a human genomic clone hgE2-14 containing exons 5, 6, 7 and 8 of the branched-chain alpha-ketoacid dehydrogenase E2 transacylase gene. Sequencing of exon 8 and its surrounding intronic sequences reveals complete identity with the previously reported truncated E2 cDNA (hE2-1) sequence between nucleotides 938 and 1521. We have identified consensus splice site junctions flanking exon 8 and also a cryptic 3' splice site 370 bases upstream from the start of exon 8 in the gene. In addition, two polyadenylation signals located in the hE2-1 cDNA are also present in the intronic sequence downstream of exon 8 which promote termination of transcription. The data indicate that shortened human liver E2 transcripts undergo alternative splicing to yield mRNA of the hE2-1 type.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗