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Biomedical subjects

T Kuo

Publications and source records attributed to T Kuo.

At least 19 recordsLinked to original sources

Anomalous decrease in groundwater radon before the Taiwan M6.8 Chengkung earthquake.

On December 10, 2003, an earthquake of magnitude (M) 6.8, the strongest since 1951, occurred near the Chengkung area in eastern Taiwan. Approximately 65 d prior to the 2003 Chengkung earthquake, precursory changes in the groundwater radon concentration were observed at the Antung radon-monitoring station located 20 km from the epicenter. The radon anomaly was a decrease from a background level of 28.9 BqL(-1) to a minimum of 12.2 BqL(-1). Observations at the Antung hot spring suggest that the groundwater radon, when observed under suitable geological conditions, can be a sensitive tracer for strain changes in the crust preceding an earthquake.

Disasters↗

Intrahepatic cholangiocarcinoma with lymphoepithelioma-like component.

We present two cases of intrahepatic cholangiocarcinoma with lymphoepithelioma-like component. The patients included one woman and one man, aged 67 and 41 years, respectively. They presented with right upper quadrant pain and epigastralgia. Histologically, both tumors showed two distinct histological patterns with dense lymphoplasma cell infiltration. The first pattern was a well to moderately differentiated adenocarcinoma; the second component showed a feature similar to lymphoepithelioma-like carcinoma. Granulomatous reaction was noted in one case. Immunohistochemical study revealed that both tumors were immunoreactive with AE1/AE3, cytokeratin 7, and cytokeratin 19 but negative for carcinoembryonic antigen and cytokeratin 20. The stromal lymphocytes were composed of predominantly CD3(+) T cells. In situ hybridization for Epstein-Barr virus (EBV)-encoded RNA (EBER) showed positive nuclear signal in tumor cells but not in inflammatory cells in one case. The presence or absence of EBV genome was confirmed by polymerase chain reaction of LMP-1 gene in both cases. The LMP-1 gene also had a 30-bp deletion in Exon 3 as compared with the products from B95-8 cells. We further sequenced the PCR product and confirmed a 30-bp deletion between Nucleotide (nt) 168,282 and nt 168,253 corresponding to the B95-8 sequence. The clinical significance of 30-bp deletion in Exon 3 of the LMP-1 gene in lymphoepithelioma-like carcinoma of the liver warrants further investigation.

Adaptor Proteins, Signal Transducing↗

Salivary gland type nasopharyngeal carcinoma: a histologic, immunohistochemical, and Epstein-Barr virus study of 15 cases including a psammomatous mucoepidermoid carcinoma.

Salivary gland type nasopharyngeal carcinomas (NPCs) are rare and not well characterized. Fifteen NPCs with adenocarcinomatous differentiation were studied for their histologic types, immunohistochemical features, and association with Epstein-Barr virus (EBV) by EBER in-situ hybridization (ISH) and by polymerase chain reaction (PCR) to detect latent membrane protein-1 (LMP-1) gene with formalin-fixed, paraffin-embedded tissues. Two cases of conventional NPC were included for comparison. The prevalence rate of salivary gland type NPCs was 1.3% of the total NPCs in this series. The patients consisted of 11 men and 4 women with ages ranging from 15 to 74 years (median, 50 yrs). Mucoepidermoid carcinoma was the most common type (53%) and an unusual psammomatous variant was found. Others were adenoid cystic carcinomas and various adenocarcinomas, including a papillary adenocarcinoma. A composite tumor of adenocarcinoma and undifferentiated carcinoma was also observed. The tumors were positive for AE1 and CK19 and generally negative for AE3 and CK20. Most cases were positive for epithelial membrane antigen and CA 19-9 with sporadic expression of carcinoembryonic antigen (CEA) and S-100 protein. Conventional NPC differed only in consistent immunonegativity for CA19-9 and CEA. EBV was detected by EBER ISH in 9 of 15 cases (60%) and by PCR of the LMP-1 gene in 10 of 15 cases (67%). Six of 10 LMP-1 gene-positive cases (60%) had a specific deletion of 30-base pairs (bp) of the LMP-1 gene. The result also supports the possible importance of a 30-bp deletion in conferring the oncogenecity of the LMP-1 gene. The prognosis of this series of salivary gland type NPCs was poor. Six of 13 patients with follow-up information already died of the disease with a median survival of only 1 year.

Adenocarcinoma↗

Histologic types of thymoma associated with pure red cell aplasia: a study of five cases including a composite tumor of organoid thymoma associated with an unusual lipofibroadenoma.

The histologic type of thymomas associated with pure red cell aplasia (PRCA) has generally been regarded to be predominantly the spindle cell type. The 5 thymomas associated with PRCA we studied showed various histologic types and none of them was a spindle cell thymoma. Some cases reported as spindle cell thymoma associated with PRCA in the literature might not be spindle cell type. The discrepancy could be due to the lack of consensus in the histologic classification of thymomas in the past. Our study showed that thymomas associated with PRCA lacked a strong correlation with a particular histologic type and the pathogenesis of PRCA associated with thymoma did not seem to be related to the histologic type. One of our cases was an unusual composite tumor of an organoid thymoma (WHO type B1) and a hitherto undescribed "lipofibroadenoma." The clinical outcome was influenced by the invasive character and the histologic type of the thymoma.

Adult↗

Dermatofibroma is a clonal proliferative disease.

Benign fibrous histiocytoma of the skin or dermatofibroma (DF) has been regarded as a fibrohistiocytic tumor. Whether DF is a neoplastic growth or a reactive process has not been settled. Since a neoplastic process is clonal in nature, clonal analysis of DF was conducted to see if DF is a clonal disease. Fresh specimens of 13 DFs and 2 hypertrophic scars obtained from female patients were studied. The adjacent nonlesional skin tissues served as controls. The clonal analysis was based on the methylation pattern of the polymorphic X-chromosome linked androgen-receptor gene (HUMARA). Eight DFs and 1 hypertrophic scar were heterozygous at the androgen receptor gene and could be analyzed. All 8 informative DFs showed a significant reduction in one of the allelic bands compared with the corresponding bands of the nonlesional tissue after Hha I digestion. Therefore, DF is a clonal proliferative disease. In contrast, 1 hypertrophic scar showed a polyclonal pattern of X-chromosome inactivation. We conclude that DF is a clonal disease favoring a neoplastic process.

Alleles↗

Pseudorabies virus membrane proteins gI and gE facilitate anterograde spread of infection in projection-specific neurons in the rat.

The membrane proteins gI and gE of Pseudorabies virus (PRV) are required for viral invasion and spread through some neural pathways of the rodent central nervous system. Following infection of the rat retina with wild-type PRV, virus replicates in retinal ganglion neurons and anterogradely spreads to infect all visual centers in the brain. By contrast, gI and gE null mutants do not infect a specific subset of the visual centers, e.g., the superior colliculus and the dorsal lateral geniculate nucleus. In previous experiments, we suggested that the defect was not due to inability to infect projection-specific retinal ganglion cells, because mixed infection of a gE deletion mutant and a gI deletion mutant restored the wild-type phenotype (i.e., genetic complementation occurred). In the present study, we provide direct evidence that gE and gI function to promote the spread of infection after entry into primary neurons. We used stereotaxic central nervous system injection of a fluorescent retrograde tracer into the superior colliculus and subsequent inoculation of a PRV gI-gE double null mutant into the eye of the same animal to demonstrate that viral antigen and fluorescent tracer colocalize in retinal ganglion cells. Furthermore, we demonstrate that direct injection of a PRV gI-gE double null mutant into the superior colliculus resulted in robust infection followed by retrograde transport to the eye and replication in retinal ganglion neuron cell bodies. These experiments provide additional proof that the retinal ganglion cells projecting to the superior colliculus are susceptible and permissive to gE and gI mutant viruses. Our studies confirm that gI and gE specifically facilitate anterograde spread of infection by affecting intracellular processes in the primary infected neuron such as anterograde transport in axons or egress from axon terminals.

Animals↗

Biochemical and genetic conservation of fission yeast Dsk1 and human SR protein-specific kinase 1.

Arginine/serine-rich (RS) domain-containing proteins and their phosphorylation by specific protein kinases constitute control circuits to regulate pre-mRNA splicing and coordinate splicing with transcription in mammalian cells. We present here the finding that similar SR networks exist in Schizosaccharomyces pombe. We previously showed that Dsk1 protein, originally described as a mitotic regulator, displays high activity in phosphorylating S. pombe Prp2 protein (spU2AF59), a homologue of human U2AF65. We now demonstrate that Dsk1 also phosphorylates two recently identified fission yeast proteins with RS repeats, Srp1 and Srp2, in vitro. The phosphorylated proteins bear the same phosphoepitope found in mammalian SR proteins. Consistent with its substrate specificity, Dsk1 forms kinase-competent complexes with those proteins. Furthermore, dsk1(+) gene determines the phenotype of prp2(+) overexpression, providing in vivo evidence that Prp2 is a target for Dsk1. The dsk1-null mutant strain became severely sick with the additional deletion of a related kinase gene. Significantly, human SR protein-specific kinase 1 (SRPK1) complements the growth defect of the double-deletion mutant. In conjunction with the resemblance of dsk1(+) and SRPK1 in sequence homology, biochemical properties, and overexpression phenotypes, the complementation result indicates that SRPK1 is a functional homologue of Dsk1. Collectively, our studies illustrate the conserved SR networks in S. pombe consisting of RS domain-containing proteins and SR protein-specific kinases and thus establish the importance of the networks in eucaryotic organisms.

Amino Acid Sequence↗

Radiofrequency tissue ablation of the inferior turbinates using a thermocouple feedback electrode.

OBJECTIVE: The objective of this clinical trial was to assess the safety and efficacy of radiofrequency (RF) tissue ablation of the inferior turbinates in the treatment of nasal obstruction using an RF energy delivery system with a thermocouple feedback electrode. METHODS: A prospective, nonrandomized study of 11 patients (mean age, 47+/-12 y) with chronic nasal obstruction was conducted. Using patient-based visual analogue scales (VAS), symptom parameters were assessed. These included degree of nasal obstruction, frequency of nasal obstruction, and pain. Physician assessment of nasal obstruction was also collected by the principal investigator. Follow-up was conducted at 24 hours, 1 week, 4 weeks, 8 weeks, and 1 year. ANOVA was carried out to determine statistically significant differences in the data. Data were fit to a regression model, and confidence intervals were determined from a 95% confidence level. RESULTS: In patient-assessed degree of nasal obstruction, statistical significance was seen among baseline and 4 weeks, 8 weeks, and 1 year (P<.001, P<.0001, and P<.0008, respectively). There was no difference between 8 weeks and 1 year (P<.15). The data appeared to follow an exponential decay to a constant value. The pretreatment baseline average degree of obstruction was 7.5+/-0.5 on a scale of 0 to 10. The degree of obstruction after 8 weeks was 2.7+/-0.6. The time constant for this change was 21 days to reach 90% of the final value. At 1 year, degree of obstruction was 3.3+/-0.7. For frequency of nasal obstruction, statistical significance was seen among baseline and 4 weeks, 8 weeks, and 1 year (P<.0001, P<.0001, and P<.0001, respectively). There was no difference between 8 weeks and 1 year (P<.15). The pretreatment baseline average frequency of obstruction was 7.8+/-0.5. The remaining frequency of obstruction after 8 weeks was 2.9+/-0.6. The time constant was 18 days. At 1 year, frequency of obstruction was 3.3+/-0.6. Physician assessment of nasal obstruction revealed statistical significance among baseline and 4 weeks, and baseline and 8 weeks (P<.0055 and P<.0056, respectively). There was no difference between 4 weeks and 8 weeks (P<.24). The average initial obstruction was 83%+/-4%. The remaining obstruction after 8 weeks was 58% +/-5%. The time constant was 14 days. Mild pain was reported by 55% of patients during the procedure; the remaining 45% reported no pain. Only one patient required pain medication consisting of acetaminophen after the procedure. There were no significant complications. CONCLUSIONS: Degree and frequency of nasal obstruction, as reported by patients, decreased following RF tissue ablation of the inferior turbinates. This improvement in symptoms was still evident after 1 year (P<.001). Physician assessment of obstruction also correlated with patient reports for the initial 8-week study period. The procedure was safe and well tolerated. Thermocouples within the active electrode provided additional feedback to the operating surgeon allowing the use of relatively lower tissue temperatures, power, and energy as compared with traditional techniques. These results support the need for continued research to evaluate this modality as a treatment for chronic nasal obstruction.

Adult↗

Ablation of Teflon granulomas in the canine larynx with the free-electron laser.

This study develops a canine model for the treatment of laryngeal Teflon granulomas and demonstrates endoscopic ablation using the free-electron laser (FEL) set at a wavelength of 8.5 microm. Laryngeal Teflon granulomas may cause dysphonia and airway obstruction, and they are difficult to remove. The infrared absorption spectrum of Teflon reveals a strong absorption peak centered at 8.5 microm. In this study, 12 dogs had the right vocal cord injected with Teflon paste. Two months later, Teflon granuloma formation was confirmed histologically. Laser incisions into the granulomas were performed at 3 different wavelengths: 7.4 microm (FEL), 8.5 microm (FEL), and 10.6 microm (carbon dioxide laser). Histopathologic analysis was performed at 1 week and 6 weeks after the laser incisions. The FEL at the 8.5-microm wavelength was found to optimally ablate the Teflon granulomas, but the granulomas persisted in the specimens treated with 7.4 microm (FEL) and 10.6 microm (carbon dioxide laser).

Animals↗

Functional interaction between InsP3 receptors and store-operated Htrp3 channels.

Calcium ions are released from intracellular stores in response to agonist-stimulated production of inositol 1,4,5-trisphosphate (InsP3), a second messenger generated at the cell membrane. Depletion of Ca2+ from internal stores triggers a capacitative influx of extracellular Ca2+ across the plasma membrane. The influx of Ca2+ can be recorded as store-operated channels (SOC) in the plasma membrane or as a current known as the Ca2+-release-activated current (I(crac)). A critical question in cell signalling is how SOC and I(crac) sense and respond to Ca2+-store depletion: in one model, a messenger molecule is generated that activates Ca2+ entry in response to store depletion; in an alternative model, InsP3 receptors in the stores are coupled to SOC and I(crac). The mammalian Htrp3 protein forms a well defined store-operated channel and so provides a suitable system for studying the effect of Ca2+-store depletion on SOC and I(crac). We show here that Htrp3 channels stably expressed in HEK293 cells are in a tight functional interaction with the InsP3 receptors. Htrp3 channels present in the same plasma membrane patch can be activated by Ca2+ mobilization in intact cells and by InsP3 in excised patches. This activation of Htrp3 by InsP3 is lost on extensive washing of excised patches but is restored by addition of native or recombinant InsP3-bound InsP3 receptors. Our results provide evidence for the coupling hypothesis, in which InsP3 receptors activated by InsP3 interact with SOC and regulate I(crac).

Animals↗

Presence of activated ras correlates with increased cysteine proteinase activities in human colorectal carcinomas.

The metastatic potential of ras-transfected cells has been attributed in part to significant ras induction of proteinase expression. To determine whether primary cancers also demonstrate higher cysteine proteinase activities in the presence of activated ras genes or altered ras protein expression, we have analyzed 60 primary human colorectal carcinomas for ras gene or protein changes together with the expression of cathepsins B and L. Cancers containing K-ras mutations (47% of 60 carcinomas) demonstrated greater increases in cathepsin L activity than cancers without K-ras mutations (p = 0.029), with particularly significant correlations for earlier stage cancers (Dukes' A and B carcinomas, p = 0.006). Western blots used to characterize ras protein patterns in the same cancer/normal pairs have demonstrated that N-ras protein is more highly expressed in colon tissues than H- or K-ras proteins and that N-ras overexpression occurs in almost 70% of colorectal cancers, with or without a concurrent change in electrophoretic mobility of N-ras protein. Our current study has now shown that N-ras protein overexpression alone does not significantly induce cathepsin B or L activity levels in colon cancers. However, carcinomas demonstrating altered N-ras protein forms, in the absence of any K- or N-ras mutations, expressed significantly higher levels of cathepsin B and L activities compared with carcinomas with normal N-ras protein banding patterns. Our data suggest that colorectal carcinomas with either K-ras mutations or altered forms of N-ras protein may increase their tumorigenic potential via the induction of cathepsin L or B expression levels. Our results also confirm that ras oncogene up-regulation of cathepsin B and L activities, previously reported in cultured cells, is a frequent event in primary human colorectal carcinomas.

Blotting, Western↗

Optimizing fluence and debridement effects on cutaneous resurfacing carbon dioxide laser surgery.

OBJECTIVE: To develop methods to compare carbon dioxide (CO2) resurfacing lasers, fluence, and debridement effects on tissue shrinkage and histological thermal denaturation. DESIGN: In vitro human or in vivo porcine skin samples received up to 5 passes with scanner or short-pulsed CO2 resurfacing lasers. Fluences ranging from 2.19 to 17.58 J/cm2 (scanner) and 1.11 to 5.56 J/cm2 (short pulsed) were used to determine each laser's threshold energy for clinical effect. Variable amounts of debridement were also studied. MAIN OUTCOME MEASURES: Tissue shrinkage was evaluated by using digital photography to measure linear distance change of the treated tissue. Tissue histological studies were evaluated using quantitative computer image analysis. RESULTS: Fluence-independent in vitro tissue shrinkage was seen with the scanned and short-pulsed lasers above threshold fluence levels of 5.9 and 2.5 J/cm2, respectively. Histologically, fluence-independent thermal depths of damage of 77 microns (scanner) and 25 microns (pulsed) were observed. Aggressive debridement of the tissue increased the shrinkage per pass of the laser, and decreased the fluence required for the threshold effect. In vivo experiments confirmed the in vitro results, although the in vivo threshold fluence level was slightly higher and the shrinkage obtained was slightly lower per pass. CONCLUSIONS: Our methods allow comparison of different resurfacing lasers' acute effects. We found equivalent laser tissue effects using lower fluences than those currently accepted clinically. This suggests that the morbidity associated with CO2 laser resurfacing may be minimized by lowering levels of tissue input energy and controlling for tissue debridement.

Animals↗

Bone marrow failure and myelofibrosis in a case of PVP storage disease.

"PVP storage disease" is a disorder occurring in patients who have received high molecular weight polyvinylpyrrolidone (PVP), which cannot be excreted from the body. These large polymers deposit in the histiocytes and cause proliferation and infiltration of histiocytes in the reticuloendothelial system. There was usually no significant damage to these organs except that prolonged administration might cause bone destruction, skin lesions, arthritis, and polyneuropathy. We describe a patient who had received a large amount of PVP-containing solution for years. Severe bone marrow failure with extensive infiltration of bone marrow by foamy histiocytes occurred later. In addition, she suffered from multiple pathological fractures with spinal cord compression and arthritis of bilateral knee joints.

Adult↗

Collagen thermal damage and collagen synthesis after cutaneous laser resurfacing.

BACKGROUND AND OBJECTIVE: Objectively measure and compare postoperative collagen thermal damage and subsequent new collagen synthesis after cutaneous laser resurfacing using two carbon dioxide laser systems. STUDY DESIGN/MATERIALS AND METHODS: We created 240 resurfacing wounds on eight piglets with scanned and short-pulsed lasers using the manufacturer's suggested settings. The wounds varied with respect to the number of laser passes and postoperative survival times. Samples were harvested for histological analysis. RESULTS: The scanned laser resulted in an average of 52% more collagen thermal damage on the day of surgery (P < 0.0001) and an average of 78% more thermal damage 3 days postoperative (P < 0.0001) than the short-pulsed laser. The amount of new collagen synthesis correlated with the amount of thermal damage, with the scanned laser wounds showing 44% greater new collagen synthesis than the short-pulsed laser wounds on postoperative day 7 (P < 0.0001) and 48% greater new collagen synthesis on postoperative day 14 (P < 0.0001). CONCLUSION: Compared to the short-pulsed laser, the scanned laser results in a greater depth of collagen thermal damage with a correspondingly greater depth of new collagen synthesis after cutaneous resurfacing.

Animals↗

N-ras protein: frequent quantitative and qualitative changes occur in human colorectal carcinomas.

Point mutation and overexpression are recognized mechanisms for ras activation in malignancy. However, little information is available on overexpression of N-ras protein compared with H- or K-ras proteins, as N-ras-specific antibodies have only recently become available. For comparative analyses of ras protein levels, we have probed Western blots of extracts from 9 normal human tissues and 55 pairs of colorectal carcinoma and matched control mucosa, using monoclonal antibodies (MAbs) specific for H-, K- or N-ras proteins. On multi-tissue blots, N-ras protein was more highly expressed in colon than in the other human tissues analyzed, suggesting a role for N-ras in colorectal function. N-ras protein levels in multiple independent extracts of normal colon mucosa were consistently higher than either K-ras protein or H-ras protein levels. In 69% of colon carcinomas, N-ras protein levels were increased an average of 4.8-fold over normal mucosa. Overexpression of K-ras protein was also observed in colon cancers but less frequently (13% of cases) than N-ras protein. H-ras protein levels were too low for comparative studies. Alterations in N-ras protein mobility, possibly reflecting increased post-translational processing, were also detected in 42% of colon carcinomas. N-ras protein, typically present as a single 23 kDa band in normal mucosa, was expressed in some cancers as a 22 kDa band or as multiple bands of 20-23 kDa. Sequencing of N-ras DNA from 6 carcinomas with these variations in protein mobility did not reveal mutations in codons 12, 13, 59 or 61. Thus, frequent quantitative and qualitative changes in N-ras protein expression, which do not appear to correlate with the presence of typical N-ras point mutations, result in abnormal N-ras protein patterns in human colorectal carcinomas.

Antibodies, Monoclonal↗

Lymphoepithelioma-like salivary gland carcinoma in Taiwan: a clinicopathological study of nine cases demonstrating a strong association with Epstein-Barr virus.

AIMS: Lymphoepithelioma-like carcinoma (LELC) of the salivary glands is a rather rare tumour. Previous studies have shown its strong association with Epstein-Barr virus (EBV) among Chinese and Eskimos. We tested this observation with nine Chinese patients with salivary gland LELC in Taiwan including one with coexisting nasopharyngeal carcinoma (NPC) and studied the prognostic significance of their histopathological features. METHODS AND RESULTS: This series showed a predilection for female patients and parotid glands with a median age of 50 years. Three patients died 18.5-26 months after the diagnosis including the case with NPC. Six patients were alive without recurrence for 14-45 months with a median follow-up of 34.5 months. Histopathologically, the tumours showed either lobular or diffuse growth pattern. Granulomas and/or germinal centres were observed in most cases and both B- and T-cells were found in the lymphoid infiltrates, indicating that the salivary gland LELC was capable of inducing a strong host immune reaction. Microscopic growth pattern, lymph node metastasis, and presence or absence of granulomas and/or germinal centres seemed to be important prognostic factors. Both salivary gland LELC and NPC shared similar histopathological appearance and positive immunostaining for epithelial membrane antigen and cytokeratin AE1 but not AE3. Granulomas and amyloid might occur in both tumours. A nasopharyngeal examination is indicated in patients with salivary gland LELC to exclude the possibility of coexisting or metastatic NPC. All nine cases showed positive nuclear signals for EBV-encoded RNA by in situ hybridization including the case with NPC. CONCLUSIONS: Our study and the previously published studies show that the association of salivary gland LELC and EBV is strongly related to racial and geographical factors.

Adolescent↗

Immunohistochemical metallothionein expression in thymoma: correlation with histological types and cellular origin.

Metallothioneins (MTs) are low molecular weight and cysteine-rich intracellular proteins involved in metal homeostasis and detoxication. They are found in certain normal tissues, and are overexpressed in various tumours with correlation to more aggressive behaviour in certain tumours. Since the histopathological types of thymoma have unpredictable invasive potential, MT over-expression was investigated as a possible marker of the invasive potential of thymomas. We studied immunohistochemical MT expression in 27 non-invasive thymomas, 20 micro-invasive thymomas, and 23 macro-invasive thymomas with a mouse monoclonal anti-MT antibody E9 on formalin-fixed paraffin-embedded tissues. MT expression was significantly different among the three groups of thymomas (P = 0.02) with a stronger expression in invasive thymomas (P = 0.003). However, MT expression was not exclusively limited to invasive thymomas. Therefore, it could not be used as a marker of aggressive potential in individual thymomas. Analysis of MT expression according to the histological types of the thymomas revealed that eight of nine spindle cell thymomas, none of 10 small polygonal cell thymomas, four of 14 mixed thymomas, seven of 29 large polygonal cell thymomas, and seven of eight squamoid thymomas significantly expressed MT. There was a statistically significant difference in MT expression among different histological types of thymomas (P = 0.000). The strongest and most consistent expression was observed in spindle cell thymoma and squamoid thymoma. Since spindle cell thymoma was usually non-invasive and squamoid thymoma was more aggressive, MT expression does not correlate with the invasive potential of different histological types of thymomas. But because medullary epithelial cells of the thymus were positive for MT, our results suggest that both spindle cell thymoma and squamoid thymoma might derive from the medullary compartment of the thymus.

Animals↗

Influence of DNA sequence identity on efficiency of targeted gene replacement.

We have developed a system for analyzing recombination between a DNA fragment released in the nucleus from a single-copy plasmid and a genomic target in order to determine the influence of DNA sequence mismatches on the frequency of gene replacement in Saccharomyces cerevisiae. Mismatching was shown to be a potent barrier to efficient gene replacement, but its effect was considerably ameliorated by the presence of DNA sequences that are identical to the genomic target at one end of a chimeric DNA fragment. Disruption of the mismatch repair gene MSH2 greatly reduces but does not eliminate the barrier to recombination between mismatched DNA fragment and genomic target sequences, indicating that the inhibition of gene replacement with mismatched sequences is at least partially under the control of mismatch repair. We also found that mismatched sequences inhibited recombination between a DNA fragment and the genome only when they were close to the edge of the fragment. Together these data indicate that while mismatches can destabilize the relationship between a DNA fragment and a genomic target sequence, they will only do so if they are likely to be in the heteroduplex formed between the recombining molecules.

Base Sequence↗