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Biomedical subjects

L Mao

Publications and source records attributed to L Mao.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Long term effect of thymectomy for patients with myasthenia gravis].

OBJECTIVE: To evaluate the long term effect of thymectomy for patients with myasthenia gravis. METHODS: Patients with myasthenia gravis 4 - 54 months after thymectomy were followed up. RESULTS: 124 patients with myasthenia gravis were treated by thymectomy from April 1990 to August 1994. The mean age at the time of surgery was 29.2. According to the modified Osserman classification. 29 patients were type I, 23 type II a, 41 type II b and 11 type III. After thymectomy 82.7% patients had good response to the operation. 13.5% had no response and 1.9% were even worse. Of 104 patients followed up, no early death was found and late death occurred in 2. Type II patients and those with shorter preoperative course responded better. CONCLUSIONS: The surgical outcome is related to clinical classification of myasthenia gravis and the duration of preoperative period. Sex and pathologic type of thymus lesion seem to be irrelevant factors to the surgical outcome. To perform thymectomy or not should be very carefully weighed for patients younger than 10 years of age.

Adolescent↗
PubMed1998

Phenotype and genotype of advanced premalignant head and neck lesions after chemopreventive therapy.

BACKGROUND: The goal of chemoprevention is to reduce the risk of cancer development by reversing or blocking the tumorigenic process through the use of pharmacologic or natural agents. To determine the potential role of genetic alterations in assessing cancer risk and in evaluating the efficacy of chemopreventive agents, we studied 22 patients with advanced premalignant lesions of the head and neck who were part of a prospective cancer prevention trial that is investigating a regimen of 13-cis-retinoic acid, interferon alfa, and alpha-tocopherol administered for 12 months or until disease progression. METHODS: We used polymerase chain reaction analysis of microsatellite DNA sequences in cells from precancerous lesions to determine the frequencies of genetic alterations--namely, loss of heterozygosity (LOH) and microsatellite instability--at chromosomal loci that are commonly deleted in head and neck cancer. RESULTS: Prior to treatment, 17 (81%) of 21, eight (44%) of 18, and eight (42%) of 19 patients who were informative (i.e., heterozygous) at chromosomes 9p21, 3p14, and 17p13, respectively, exhibited LOH in at least one of their lesion biopsy specimens. Among nine patients who exhibited LOH at chromosome 9p21 in pretreatment biopsy specimens and who had completed at least 5 months of therapy, the genetic loss persisted in eight--including three of the four patients who exhibited complete histologic responses (i.e., no evidence of dysplasia in their biopsy specimens). IMPLICATION: Our data suggest that clinical and histologic assessments of the response to chemopreventive agents may be insufficient to determine their efficacy and that critical genetic alterations could be used as independent biomarkers to augment the ability to evaluate the efficacy of such agents.

Antineoplastic Agents↗
PubMed1998

Identification of two distinct tumor-suppressor loci on the long arm of chromosome 10 in small cell lung cancer.

Recent cytogenetic studies indicated that loss of the long arm of chromosome 10 is a frequent event in small cell lung cancer (SCLC) and that a common region of the deletion is at 10q24-qter, which suggests the presence of a tumor-suppressor gene there. To map precise tumor-suppressor loci on the chromosome arm for further positional cloning efforts, we tested 46 primary SCLCs using microsatellite analysis. By analysing 11 highly polymorphic microsatellite markers located in 10q23-q26, we found that at least 78% (36/46) of the tumors exhibited loss of heterozygosity (LOH) at 10q with at least two distinct minimally deleted regions. LOH at one region (10q24) was found in at least 74% (32/43) of informative cases with a minimally deleted region between D10S198 and D1OS192 (about 2 cM); LOH at another region (10q24-q25) was observed in at least 66% (29/44) of informative tumors with a minimally deleted region between D10S221 and D10S587 (about 11 cM). LOH at both regions or across both regions was observed in at least 52% (24/46) of the tumors tested. However, no mutations or homozygous deletions were found in the coding region of MXI1, a candidate tumor suppressor gene at 10q24-q25, in a panel of SCLC cell lines. Our data demonstrate that at least two tumor-suppressor loci exist on 10q and that they may play an important role in SCLC tumorigenesis.

Adult↗
PubMed1998

Overexpression of cdc25A and cdc25B is frequent in primary non-small cell lung cancer but is not associated with overexpression of c-myc.

Cyclin-dependent kinases can be activated by cdc25, which removes inhibitory phosphates from tyrosine and threonine residues. At least three cdc25 genes (cdc25A, cdc25B, and cdc25C) have been identified in humans. Accumulating evidence indicates that cdc25A and cdc25B possess oncogenic properties. Recently, overexpression of cdc25A and of cdc25B was found in many breast and head and neck cancers. To determine potential roles of cdc25s in non-small cell lung cancer (NSCLC), we analyzed primary tumors and corresponding normal lung tissues from 40 patients with NSCLC for relative expression levels of these genes by multiplex reverse transcription PCR (RT-PCR). cdc25A was overexpressed in 60% (24 of 40) of the tumors and cdc25B in 45% (18 of 40) of the tumors, whereas cdc25C was not overexpressed in any of the tumors analyzed. Because c-myc can increase cdc25A and cdc25B expression, it may be a factor in cdc25 overexpression. We found that c-myc was overexpressed in only 18% (7 of 40) of the tumors. We found no association between overexpression of c-myc and cdc25A or cdc25B. We also investigated whether the cdc25B gene was amplified in NSCLC and found this was true in 40% (8 of 20) of the tumors tested. However, this amplification was not correlated with gene expression status. Interestingly, among 24 tumors with cdc25A overexpression and 18 with cdc25B overexpression, 42% (10 of 24) and 44% (8 of 18) were poorly differentiated histological type. In contrast, well or moderately differentiated tumors had lower frequencies of cdc25A and cdc25B overexpression [19% (3 of 16) and 23% (5 of 22), respectively]. These data indicate that overexpression of cdc25A and cdc25B is frequent and that it may play an important role in NSCLC. However, it is unlikely that this overexpression is caused by c-myc stimulation or cdc25B gene amplification.

Adenocarcinoma↗
PubMed1998

TSG101 is not mutated in lung cancer but a shortened transcript is frequently expressed in small cell lung cancer.

TSG101 is a candidate tumor suppressor gene whose deletion in NIH3T3 cells leads to spontaneous lung metastases in nude mice. Aberrant transcripts of TSG101 have been identified in 47% of primary breast carcinomas, without evidence of intragenic deletions at the TSG101 locus on 11p15. To investigate the possible role of TSG101 in lung cancer, which often shows 11p allele loss, we performed transcript analysis and mutational analysis of TSG101 in lung cancer cell lines. Reverse transcriptase RT-PCR and Northern analysis detected a common TSG101 transcript, shortened because of an internal deletion, which was expressed simultaneously with the wild-type transcript in 89% of small cell lung cancer (SCLC) lines. In contrast, the wild-type transcript was expressed alone in normal tissues, primary non-small cell lung cancer (NSCLC) specimens, and the majority of NSCLC cell lines. Sequence of the shortened SCLC transcript was identical to that of the most common aberrant transcript identified in breast cancer, consisting of a deletion of exons 2-4 and part of 1 and 5. Southern analysis of SCLC lines expressing the shortened transcript did not detect any intragenic deletions. Single strand conformational polymorphism (SSCP) analysis and direct sequencing of TSG101 cDNAs also identified no mutations or deletions. These results suggest that TSG101 is not mutated in lung cancer but that aberrant splicing of TSG101 occurs in SCLC.

Blotting, Northern↗
PubMed1998

Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines.

Loss of heterozygosity (LOH) at chromosome 10q23-q25 is frequent in small cell lung cancer (SCLC), indicating the presence of putative tumor suppressor genes. PTEN/ MMAC1, a newly cloned candidate tumor suppressor gene at 10q23, was mutated in multiple human cancers. We investigated whether mutations of PTEN/MMAC1 play an important role in SCLC tumorigenesis. We examined 16 SCLC cell lines for PTEN/MMAC1 mRNA expression by reverse-transcriptase polymerase chain reaction (RT-PCR) and potential mutations by sequencing analysis of the PTEN/MMAC1 coding region. No mutation was observed in PTEN/MMAC1 cDNAs in 15 cell lines expressing PTEN/MMAC1. One SCLC cell line, DMS79, did not have detectable PTEN/ MMAC1 expression. Importantly, we identified a novel homologue of PTEN/MMAC1, termed PTH2, localized to chromosome 9p21-q13 and containing only ten amino acid substitutions compared with the PTEN/MMAC1 coding region. However, because the putative initiation codon for PTEN/MMAC1 gene was changed to arginine in PTH2, the translational initiation site of PTH2 is very likely to differ from that of the PTEN/MMAC1. PTH2 was expressed in two normal lung tissues and two normal colon tissues, but in only four of 16 SCLC cell lines. A missense mutation in PTH2 was identified in a SCLC cell line that did not express PTEN/MMAC1 mRNA. Our data suggest that inactivation of PTEN/ MMAC1 is a rare event in SCLC tumorigenesis. However, the PTEN/MMAC1 homologue PTH2 may play a role in SCLC tumorigenesis.

Amino Acid Sequence↗
PubMed1998

Angiotensin II blockade followed by growth hormone as adjunctive therapy after experimental myocardial infarction.

BACKGROUND: Recombinant human growth hormone (rhGH) has shown beneficial effects on cardiac function after myocardial infarction (MI) in rats. High-dose angiotensin II (AT1) receptor blockade in normal rats inhibited the hypertrophic effect of growth hormone (GH), therefore we investigated whether GH effects after MI would be enhanced by giving it in sequence after remodeling had been inhibited by prior AT1 blockade (losartan, L). METHODS AND RESULTS: Rats given losartan for 10 weeks after MI followed by rhGH for 2 weeks (2 mg/kg twice a day, GH plus losartan) were compared with rats given losartan for 10 weeks followed by placebo for 2 weeks (placebo plus losartan group) and with untreated controls (n = 17-20/group). Average MI sizes and left ventricular (LV) end diastolic (ED) dimensions (echocardiography) did not differ between groups. In GH and losartan, body weight (BW) was increased but left ventricular weight (LVW)/BW was reduced, and the LV fractional shortening and LV dP/dtmax (catheter tip micromanometer) were increased compared with the control group (20.3 vs 15.4% and 5579 vs 4699 mmHg/s, respectively, P < .05). The cardiac index also was significantly increased. In the placebo plus losartan group, the LVW/BW was also reduced and the cardiac index increased versus controls. Stroke volume was increased in GH plus losartan group compared with both placebo plus losartan and controls, and the systemic vascular resistance was significantly decreased only in the GH plus losartan group. The ED posterior wall thickness (noninfarcted wall) was increased in GH plus losartan compared with both control and placebo plus losartan. Left ventricular end diastolic pressure reduction was not significant in GH plus losartan group versus controls but was reduced in placebo plus losartan group, whereas LV relaxation (tau) was improved in both groups versus control rats. Thus, persistent remodeling effects caused by prior AT1 blockade undoubtedly contributed to some responses, but short-term GH given in sequence after chronic AT1 blockade had favorable actions on the failing heart and peripheral circulation by increasing LV wall thickness with partial reversal of unfavorable remodeling, lowering of vascular resistance, improvement of LV contractility, and enhanced LV systolic function and cardiac index relatively late after experimental MI.

Angiotensin II↗
PubMed1998

Genotypic analysis of flow-sorted and microdissected head and neck squamous lesions by whole-genome amplification.

To investigate the utility of primer extension preamplification (PEP) in the genetic analysis of head and neck squamous tumorigenesis, microsatellite analysis was performed on matched deoxyribonucleic acid (DNA) samples extracted from 32 flow-sorted and microdissected specimens before and after PEP. Eighteen fresh and nine archival specimens were taken from invasive carcinomas, and five specimens were obtained from microdissected archival premalignant squamous epithelial lesions. Identical microsatellite patterns were observed in 276 (87%) of the 319 paired PEP and non-PEP genotypes with sufficient DNA. Overall, 13 (4%) of the PEP and 28 (8.8%) of the non-PEP fresh tissue samples failed specific microsatellite amplification. All 14 PEP-archival specimens were successfully amplified. Sorted cells showed a higher incidence (42.8%) of loss of heterozygosity (LOH) in both PEP and non-PEP samples compared with their unsorted counterparts. The results of this study indicate that (a) PEP is a simple and reliable technique for enhancing the DNA yield from small specimens; (b) flow sorting, in certain cases, improves the interpretation of genetic results; and (c) PEP may be used to compensate for PCR failure of unamplified DNA specimens in these lesions.

Carcinoma, Squamous Cell↗
PubMed1998

Effects of growth hormone and IGF-I on cardiac hypertrophy and gene expression in mice.

Cardiac hypertrophic and contractile responses were studied in mice administered growth hormone (GH) and insulin-like growth factor (IGF-I) (8 mg . kg-1 . day-1), alone or in combination (IGF-I/GH), for 2 wk. Also, changes in expression of selected left ventricular (LV) genes in response to IGF-I/GH were compared with those in other forms of cardiac hypertrophy. GH or IGF-I alone at three to four times the usual dose in rats failed to produce increases in heart and LV weights and hemodynamic effects; however, IGF-I/GH was synergistic, increasing body weight and LV weights by 39 and 35%, respectively. A measure of myocardial contractility (maximal first derivative of LV pressure, catheter-tip micromanometry) was increased by 34% in the IGF/GH group, related in part to a force-frequency effect, since the heart rate increased by 21%. Other mice were treated surgically to produce pressure overload (transverse aortic constriction) or volume overload (arteriovenous fistula) for 2 wk; LV weights were then matched to those in the IGF-I/GH group, and mRNA levels of selected markers were assessed. In contrast to the increased mRNA levels of atrial natriuretic factor, alpha-skeletal actin, and collagen III generally observed in overloaded hearts, changes in IGF-I/GH-treated mice were not significant. Thus high-dose IGF-I/GH produce cardiac hypertrophy and a positive inotropic effect without causing significant changes in expression of fetal and other selected myocardial genes, suggesting that this hypertrophy may be of a more physiological type than that due to mechanical overload.

Actins↗
PubMed1998

[Analysis of air pollutants with a combination of GC/FTIR and GC/MS].

In this paper, the air pollutants were analyzed with a combination of Gas chromatography/Fourier transform infrared spectroscopy (GC/FTIR) and Gas chromatography/Mass spectroscopy (GC/MS). The organic mixture was well separated after a careful adjustment of GC and IR parameters in GC/FTIR. In the identification of unknown components, MS is a main method, while IR is also useful to confirm the results.

English Abstract↗
PubMed1998

Presence of multiple incontiguous deleted regions at the long arm of chromosome 18 in head and neck cancer.

The 18q chromosomal region is frequently lost in head and neck squamous cell carcinomas (HNSCCs). Several candidate tumor suppressor genes have been mapped to this chromosomal region, including DCC, DPC4, and MADR2. The latter two genes are members of the Smad family, key downstream mediators in the transforming growth factor beta signaling pathway, and their alterations could confer resistance to transforming growth factor beta and contribute to tumorigenesis. Nevertheless, genetic alterations of DCC and DPC4 in HNSCC have not been frequently reported. To further investigate the extent and significance of the loss of the 18q chromosomal region in HNSCC, we performed detailed mapping at this region in a set of 50 primary HNSCCs using 19 highly polymorphic microsatellite markers. We detected loss of heterozygosity in 84% of the tumors tested and were able to identify three minimal deleted regions encompassing markers D18S467-D18S474 at 18q12 (4 cM), D18S1099-D18S487 at 18q21.1 (3 cM), and D18S69-41 at 18q21.1-q21.2 (2 cM). Of these minimal deleted regions, only one harbors a known candidate tumor suppressor gene, DCC, which maps telomeric to D18S46. In addition, the role of the MADR2 gene in HNSCCs was investigated by examining nine HNSCC cell lines for alterations of the gene by reverse transcription-PCR and direct sequencing analysis. No mutations or polymorphisms were detected, making this gene an unlikely target of the frequent loss at 18q in HNSCC. Our data indicate high frequency of loss of heterozygosity at 18q in HNSCC and the presence of at least two as yet unidentified tumor suppressor genes in this chromosomal region. Additional efforts to identify these putative tumor suppressor genes are warranted.

Carcinoma, Squamous Cell↗
PubMed1998

Ethanol counteraction of clonidine-evoked inhibition of norepinephrine release in rostral ventrolateral medulla of rats.

Previous studies from our laboratory demonstrated an antagonistic hemodynamic interaction between ethanol and clonidine in conscious and in urethane-anesthetized rats. The present study tested the hypothesis that ethanol produces its effect by counteracting clonidine-evoked inhibition of norepinephrine (NE) release at its major site of action, the rostral ventrolateral medulla (RVLM). In vivo electrochemical measurement of real-time changes in NE level in the RVLM of urethane-anesthetized Sprague-Dawley rats was made along with blood pressure and heart rate. Clonidine (30 microg/kg, i.v.) produced significant decreases (p < 0.05) in NE electrochemical signal and blood pressure. Ethanol (1 g/kg, i.v.) administered 10 min after clonidine significantly (p < 0.05) increased NE signal and counteracted clonidine-evoked hypotension. Equal volume of saline had no effect on NE signal in the RVLM nor on the hypotensive response to clonidine. Pretreatment with the same dose of ethanol (1 g/kg) caused slight increases in RVLM NE level and in blood pressure, but did not influence the electrochemical and blood pressure responses to clonidine; clonidine (30 microg/kg) administration 10 min after ethanol resulted in significant (p < 0.05) decreases in NE signal and blood pressure. These findings suggest that: (i) ethanol counteraction of the hypotensive action of clonidine involves, at least in part, opposite effects on central pathways that use NE as a neurotransmitter; (ii) the RVLM represents a possible site for the adverse hemodynamic interaction between ethanol and clonidine; and (iii) ethanol-evoked increase in RVLM NE, which correlates with its pressor effect, is much enhanced when RVLM NE level is reduced by clonidine.

Animals↗
PubMed1997

Genomic organization and mutation analysis of Hel-N1 in lung cancers with chromosome 9p21 deletions.

Allelic loss of chromosome 9p21 is common in small cell lung cancer (SCLC), but inactivation of the tumor suppressor gene CDKN2a is rare, implying the existence of another target gene at 9p21. A recent deletion mapping study of chromosome 9p has also identified a site of deletion in non-small cell lung cancer (NSCLC) centered around D9S126. The Hel-N1 (human elav-like neuronal protein 1) gene encodes a neural-specific RNA binding protein that is expressed in SCLC. We have mapped this potentially important gene in lung tumorigenesis to within 100 kb of the D9S126 marker at chromosome band 9p21 by using homozygously deleted tumor cell lines and fluorescence in situ hybridization to normal metaphase spreads. Hel-N1 is, therefore, a candidate target suppressor gene in both SCLC and NSCLC. We have determined the genomic organization and intron/exon boundaries of Hel-N1 and have screened the entire coding region for mutations by sequencing 14 primary SCLCs and cell lines and 21 primary NSCLCs preselected for localized 9p21 deletion or monosomy of chromosome 9. A homozygous deletion including Hel-N1 and CDKN2a was found in a SCLC cell line, and a single-base polymorphism in exon 2 of Hel-N1 was observed in eight tumors. No somatic mutations of Hel-N1 were found in this panel of lung tumors. Hel-N1 does not appear to be a primary inactivation target of 9p21 deletion in lung cancer.

Base Sequence↗
PubMed1997

Clonal genetic alterations in the lungs of current and former smokers.

BACKGROUND AND PURPOSE: Genetic damage has been identified at multiple chromosomal sites (i.e., loci) in lung cancer cells. We questioned whether similar damage could be detected in the bronchial epithelial cells of chronic smokers who do not have this disease. METHODS: Biopsy specimens from six different bronchial regions were obtained from 54 chronic smokers (40 current smokers and 14 former smokers). The presence of squamous metaplasia and dysplasia (abnormal histologic changes) in the specimens was documented by examination of hematoxylin-eosin-stained sections, and a metaplasia index ([number of biopsy specimens with metaplasia/total number of biopsy specimens] x 100%) was calculated for each subject. Loss of heterozygosity (i.e., loss of DNA sequences from one member of a chromosome pair) involving microsatellite DNA at three specific loci-chromosome 3p14, chromosome 9p21, and chromosome 17p13-was evaluated by means of the polymerase chain reaction. Fisher's exact test and logistic regression analysis were used to assess the data. Reported P values are two-sided. RESULTS: Data on microsatellite DNA status at chromosomes 3p14, 9p21, and 17p13 were available for 54, 50, and 44 subjects, respectively. The numbers of individuals who were actually informative (i.e., able to be evaluated for a loss of heterozygosity) at the three loci were 36 (67%), 37 (74%), and 34 (77%), respectively. DNA losses were detected in 27 (75%), 21 (57%), and six (18%) of the informative subjects at chromosomes 3p14, 9p21, and 17p13, respectively. Fifty-one subjects were informative for at least one of the three loci, and 39 (76%) exhibited a loss of heterozygosity. Forty-two subjects were informative for at least two of the loci, and 13 (31%) exhibited losses at a minimum of two loci. Loss of heterozygosity at chromosome 3p14 was more frequent in current smokers (22 [88%] of 25 informative) than in former smokers (five [45%] of 11 informative) (P = .01) and in subjects with a metaplasia index greater than or equal to 15% (21 [91%] of 23 informative) than in subjects with a metaplasia index of less than 15% (six [46%] of 13 informative) (P = .003). In five informative individuals among nine tested nonsmokers, a loss of heterozygosity was detected in only one subject at chromosome 3p14 (P = .03), and no losses were detected at chromosome 9p21 (P = .05). CONCLUSIONS: Genetic alterations at chromosomal sites containing putative tumor-suppressor genes (i.e., 3p14 and the FHIT gene, 9p21 and the p16 gene [also known as CDKN2], and 17p13 and the p53 gene [also known as TP53]) occur frequently in the histologically normal or minimally altered bronchial epithelium of chronic smokers.

Adult↗
PubMed1997

Cloning and genetic mapping of wheat telomere-associated sequences.

Wheat telomere-associated sequences (TASs) were cloned using a Vectorette approach and sequenced. Reverse primers specific to the TASs were combined with labelled degenerate telomere primers in PCR reactions containing total genomic DNA as template. Amplification products were separated on sequencing gels. In total, seventeen primer combinations provided 47 polymorphic fragments. Nine of these mapped beyond the most distal RFLP markers and defined the ends of seven chromosome arms. Seven of the nine terminal fragments were derived from a 118-bp tandem repeat, indicating that subtelomeric tandem repeat sequences provide an efficient means to target chromosome ends. A telomere cloning strategy and the terminal and interstitial location of TASs are discussed.

Base Sequence↗
PubMed1997

Reduced expression of mismatch repair genes measured by multiplex reverse transcription-polymerase chain reaction in human gliomas.

Microsatellite instability (MIN) is frequently observed in hereditary nonpolyposis colon cancer and in other sporadic cancers including gliomas. Abnormalities in at least one of five mismatch repair (MMR) genes are implicated in the development of cancers in hereditary nonpolyposis colon cancer and the associated MIN. Using a newly developed multiplex reverse transcription-PCR assay, we evaluated the expression of the five known human MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and GTBP) in human gliomas by measuring simultaneously the relative levels of the transcripts. The beta-actin gene was used as an internal control for RNA degradation and DNA contamination and as a reference for quantifying the levels of their transcripts. Of the 33 gliomas examined, 42% (14) had low expression of hMSH2 (at least 4-5-fold lower than normal mean), 21% (7) had low expression of hMLH1, and 18% (6) had low expression of hPMS1 compared with the expression in the lymphocytes from 13 normal individuals. Furthermore, six of the 33 (18%) tumor samples had decreased expression of more than one MMR gene. Two of these six patients with multiple gene abnormalities had second primary cancers, and an additional patient had multifocal gliomas. Further molecular analysis of available DNA samples indicated that one of five of those tumors with aberrant expression of MMR genes had MIN, as compared with none of five tumors with normal expression. These data suggest that reduced expression of MMR genes is frequent in human gliomas and that aberrant expression of more than one MMR gene may be associated with increased risk of second primary malignancies in glioma patients.

Adaptor Proteins, Signal Transducing↗