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Biomedical subjects

A Woo

Publications and source records attributed to A Woo.

At least 19 recordsLinked to original sources
PubMed2003

Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis.

OBJECTIVES: To assess patients with different types of mutations of the beta myosin heavy chain (beta MHC) gene causing hypertrophic cardiomyopathy (HCM) and to determine the prognosis of patients according to the affected functional domain of beta MHC. DESIGN AND SETTING: Cohort study of subjects referred to an HCM clinic at an academic hospital. PATIENTS: 70 probands from the HCM clinic were screened for mutations of the beta MHC gene and 148 family members of the genotype positive probands were further assessed. The control group for the genetic studies consisted of 106 healthy subjects. MAIN OUTCOME MEASURES: Direct DNA sequencing was used to screen 70 probands for mutations of the beta MHC gene. Family members underwent genotypic and detailed clinical, ECG, and echocardiographic assessments. The survival of genotype positive subjects was evaluated according to the type of functional domain affected by the missense mutation and according to phenotypic characteristics. RESULTS: A mutation of the beta MHC gene was detected in 15 of 70 probands (21%). Of 148 family members studied in these 15 families, 74 were identified with a beta MHC defect. Eleven mutations were detected, including four novel mutations: Ala196Thr, Pro211Leu, Val404Leu, and Arg870Cys. Median survival was 66 years (95% confidence interval (CI) 64 to 77 years) in all affected subjects. There was a significant difference in survival between subjects according to the affected functional domain (p = 0.02). Significant independent predictors of decreased survival were the non-conservative (that is, associated with a change in the amino acid charge) missense mutations that affected the actin binding site (hazard ratio 4.4, 95% CI 1.6 to 11.8; p = 0.003) and those that affected the rod portion of beta MHC (hazard ratio 4.8, 95% CI 1.2 to 19.4; p = 0.03). No phenotypic characteristics were associated with decreased survival or cardiovascular morbidity. CONCLUSIONS: The type of beta MHC functional domain affected by the missense mutation is predictive of overall prognosis in HCM.

Adolescent↗
PubMed2001

Risk factors for heterotopic ossification in total hip arthroplasty.

This study prospectively evaluated 928 patients with 1318 primary total hip replacements for heterotopic ossification (HO). The mean clinical and radiological follow-up was 2.5 years (range 1.5-3.6 years). HO was noted in 44.6% of all total hips replaced. It was graded as mild (Brooker 1) in 29.2%, moderate (Brooker 2) in 10.5%, and severe (Brooker 3 and 4) in 4.2%. The following factors showed a significantly increased risk of HO: hypertrophic osteoarthritis, HO after contralateral total hip replacement, trochanteric osteotomy, lateral or anterolateral approach, previous hip surgery, subtrochanteric femoral osteotomy, and male gender (p < 0.05 in chi-square analysis of independence and multivariable analysis). Patients with rheumatoid arthritis showed less HO. A combination of any of these factors resulted in a significant increase in the risk of developing HO.

Aged↗
PubMed2001

Appendectomy in patients undergoing laparoscopic surgery for pelvic pain.

STUDY OBJECTIVE: To evaluate pathologic findings in appendixes of women undergoing laparoscopic surgery for pelvic pain. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Private practice specializing in gynecologic endoscopic surgery. PATIENTS: One hundred ninety women. INTERVENTION: Prophylactic appendectomy. MEASUREMENTS AND MAIN RESULTS: On pathologic evaluation, 154 appendixes were diagnosed as having one or more abnormal findings, such as endometriosis, carcinoid, chronic appendicitis, periappendicitis, fibrous obliteration, and lymphoid hyperplasia. CONCLUSION: Women undergoing laparoscopic surgery for pelvic pain should be counseled on the high frequency of abnormal findings in the appendix, including endometriosis. Prophylactic appendectomy appears to be a worthwhile consideration in these patients.

Adolescent↗
PubMed2001

Maxillary sagittal and vertical displacement induced by surgically assisted rapid palatal expansion.

The purpose of this study was to investigate the sagittal and vertical effects on the maxilla induced by surgically assisted rapid palatal expansion. Twenty patients (average age, 25.6 years) who required a surgically assisted rapid palatal expansion procedure were available for this study. Each patient was banded with a Haas-type palatal expander, maxillary surgery was performed, and the expander was activated. Presurgical and postexpansion lateral cephalograms were taken for each patient. The measurements of SNA, Frankfort horizontal-nasion-A point, sella-nasion-palatal plane, A-point-nasion-perpendicular (in millimeters), 1-nasion-A-point, 1-sella-nasion, 1-nasion-perpendicular (in millimeters) were made on each cephalogram, and the presurgical and postexpansion tracings were superimposed on the cranial base to determine the changes in the anterior nasal spine and posterior nasal spine positions. Results showed that from the presurgical cephalogram to the postexpansion cephalogram SNA, Frankfort horizontal-nasion-A point and A-point-nasion-perpendicular had a mean increase of 0.60 degrees (P <.05), 0.65 degrees (P <.05), and 0.55 mm (P <.05), respectively; 1-nasion-A-point decreased 2.18 degrees (P <.05) and 1-sella-nasion decreased 1.53 degrees (P <.05). No significant maxillary vertical displacement was noted from the first cephalogram to the second. In conclusion, surgically assisted RPE did not significantly affect the maxilla vertically; however, it did induce a slight forward movement of the maxilla and a slight retroclination of the maxillary incisors sagittally (P <.05).

Adolescent↗
PubMed2001

Gluteus minimus-induced femoral head deformation in dysplasia of the hip.

Lateral notching of the femoral head is considered pathognomonic for spastic subluxation of the hip. Less frequently, flattening is seen with extrusion of the femoral head in nonspastic hip dysplasia. The aim of this study was to throw light on its underlying pathomechanism. On the radiographs of 297 hips with developmental dysplasia, lateral flattening of the femoral head was seen in 18 hips (6%), but notching was present in only 1. Of 7 dysplasias due to cerebral palsy, 6 showed lateral notching. The gluteus minimus was felt to be responsible for the lateral femoral head changes as the muscle counteracts lateral migration of the femoral head. Intraoperative dissection of 3 hips supported this view. 1 hip with developmental dysplasia and lateral notching was subjected to a periacetabular osteotomy. At surgery, the tendon of the gluteus minimus was found to fit tightly into the notch. Of 2 hips with spastic dysplasia, 1 presented with and the other without lateral notching. In the hip with lateral notching, the gluteus minimus had a normal appearance and it lay in the defect of the femoral head. In the hip without notching, the gluteus minimus was atrophied with signs of fatty degeneration. We therefore believe that lateral notching is a sign of hypertonicity of the gluteus minimus muscle.

Adolescent↗
PubMed2000

Modulation of glutathione S-transferase alpha by hepatitis B virus and the chemopreventive drug oltipraz.

Persistent infection by hepatitis B virus (HBV) and exposure to chemical carcinogens correlates with the prevalence of hepatocellular carcinoma in endemic areas. The precise nature of the interaction between these factors is not known. Glutathione S-transferases (GST) are responsible for the cellular metabolism and detoxification of a variety of cytotoxic and carcinogenic compounds by catalysis of their conjugation with glutathione. Diminished GST activity could enhance cellular sensitivity to chemical carcinogens. We have investigated GST isozyme expression in hepatocellular HepG2 cells and in an HBV-transfected subline. Total GST activity and selenium-independent glutathione peroxidase activity are significantly decreased in HBV transfected cells. On immunoblotting, HBV transfected cells demonstrate a significant decrease in the level of GST Alpha class. Cytotoxicity assays reveal that the HBV transfected cells are more sensitive to a wide range of compounds known to be detoxified by GST Alpha conjugation. Although no significant difference in protein half-life between the two cell lines was found, semi-quantitative reverse transcription-polymerase chain reaction shows a reduced amount of GST Alpha mRNA in the transfected cells. Because the HBV x protein (HBx) seems to play a role in HBV transfection, we also demonstrated that expression of the HBx gene into HepG2 cells decreased the amount of GST Alpha protein. Transient transfection experiments using both rat and human GST Alpha (rGSTA5 and hGSTA1) promoters in HepG2 cells show a decreased CAT activity upon HBx expression, supporting a transcriptional regulation of both genes by HBx. This effect is independent of HBx interaction with Sp1. Treatment with oltipraz, an inducer of GST Alpha, partially overcomes the effect of HBx on both promoters. Promoter deletion studies indicate that oltipraz works through responsive elements distinct from AP1 or NF-kappaB transcription factors. Thus, HBV infection alters phase II metabolizing enzymes via different mechanisms than those modulated by treatment with oltipraz.

Antiviral Agents↗
PubMed2000

Effect of denture cleansers, surface finish, and temperature on Molloplast B resilient liner color, hardness, and texture.

PURPOSE: The purpose of this study was to compare color, texture, and Shore A hardness of a resilient silicone denture liner with as-polymerized, roughened, or pumiced surfaces after treatment with perborate-, persulfate-, or hypochlorite-containing denture cleansers at 25 degrees or 55 degrees. MATERIALS AND METHODS: Fifty-eight specimens that each exhibited an as-polymerized, a roughened, and a pumiced area were exposed to 5 different commercially available perborate-, persulfate-, or hypochlorite-containing denture cleansers at 25 degrees or 55 degrees continuously for 4 (1/2) months. The solutions were replaced twice a day. Control specimens were soaked in water with no cleanser. Before and after the 4 (1/2) -month cleaning regimen, the color, hardness, and texture of resilient liner surfaces were evaluated using a color densitometer, a Shore A durometer (Shore Instrument & Mfg Co, Freeport, NY), and a surface profilometer, respectively. Differences among groups after the cleanser treatment were determined using a repeated measures analysis of variance (alpha = 0.05) and a Tukey's Honestly Significant Difference post hoc test. RESULTS: Roughened specimen surfaces after 25 degrees or 55 degrees cleanser treatment exhibited significant color loss with some perborate-containing cleansers compared with the control. Roughened specimens treated at 55 degrees with perborate-containing cleansers also exhibited significantly greater color loss than those treated with the persulfate-containing cleanser. With roughened surfaces, significantly greater hardness was found with some perborate-containing cleanser compared with a hypochlorite-containing cleanser after treatment at 25 degrees. No differences were observed in surface texture based upon cleanser treatment. CONCLUSION: After silicone resilient denture liner treatment with certain perborate-containing denture cleansers, a greater amount of components could leach from the liner leading to a loss of color if the liner surface is rough.

Analysis of Variance↗
PubMed1998

Identification of the Yc1 glutathione S-transferase mRNA as the overexpressed species in a nitrogen mustard-resistant rat mammary carcinoma cell line.

Glutathione transferase (GSTs) have been shown to be overexpressed in a number of tumor cell lines selected for resistance to chemotherapeutic drugs and have been implicated in some studies of clinical specimens. In tumor cell lines selected for resistance to chemicals that alkylate DNA, the isoform most frequently overexpressed is GST-Yc, a member of the alpha class GSTs. To date, two variations of the cDNA designated Yc1 with subtle differences have been described, and Yc2 is shown to be clearly distinct. Transfection of a Yc1 cDNA constitutively expressed in rat liver into rat mammary cancer cells confers resistance to alkylators, however, to a lesser extent than is observed in the cells selected for resistance. It has therefore been widely suggested that the GST that is overexpressed in selected resistant cells represents a distinct and novel isoform. We have previously described a rat mammary carcinoma cell line (MLNr) that is resistant to alkylating agents, and overexpresses a GST with characteristics similar to GST-Yc1 and not Yc2. It has many features common to the several other GST-Yc overexpressing alkylator resistant cell lines. We have cloned the specific Yc cDNA overexpressed in MLNr and analyzed it in detail and found that it is identical to one of the previously reported Yc1 cDNAs, suggesting that there is no additional Yc gene specifically induced by nitrogen mustards. Another hypothesis to explain the difference in the level of resistance in selected versus GST-Yc transfected cells is the lack of concurrent increased glutathione (GSH) in the transfectants, which is a common feature in the selected resistant cells. Experiments in which we modulated GSH levels suggest that this is not likely. These studies add to our speculation that other mechanisms may be involved in alkylator resistance.

Animals↗
PubMed1995

Enhanced host cell reactivation capacity and expression of DNA repair genes in human breast cancer cells resistant to bi-functional alkylating agents.

Human breast carcinoma (MCF7-MLNr) cells resistant to the bifunctional drugs L-phenylalanine mustard (L-PAM, 5-fold resistance), mechlorethamine (9-fold), cisplatin (3-fold), and BCNU (3-fold) were used to investigate the role of DNA repair in the development of resistance to alkylating agents. We have previously shown that neither L-PAM transport and metabolism nor glutathione-associated enzymes were altered in MCF7-MLNr cells, compared to the sensitive cells MCF7-WT. This study shows that treatment of pRSV-CAT plasmid with L-PAM at concentrations up to 1 microM proportionally inhibit the expression of chloramphenicol acetyl transferase (CAT) activity, while higher concentrations abolished CAT activity. pRSV-CAT reactivation was significantly increased when plasmid was transfected into MCF7-MLNr cells, compared to MCF7-WT cells. This indicates that resistant cells have more efficient capacity to recognize and repair L-PAM induced DNA damage. The mRNA expression of DNA nucleotide excision repair genes ERCC1, XPD (ERCC2), XPB (ERCC3), and polymerase beta was found to be similar in both the MCF7-WT and MCF7-MLNr cells. Western blot analysis also reveals no difference in the expression of ERCC1, AP endonuclease, poly (ADP-ribose) polymerase, and alkyl-N-purine-DNA glycosylase proteins. The lack of correlation between enhanced host cell reactivation capacity in resistant cells, and the expression of these specific DNA repair genes suggests that proteins encoded by these genes are not rate limiting steps for resistance to bi-functional alkylating drugs in human breast cancer cells.

Adenocarcinoma↗
PubMed1993

Expression of a rat glutathione-S-transferase complementary DNA in rat mammary carcinoma cells: impact upon alkylator-induced toxicity.

The role of glutathione-S-transferase (GST) in alkylator drug resistance has been studied in MatB rat mammary carcinoma cells. A series of GST transfectant cell lines was established by using an expression vector containing the complementary DNA for the rat GST Yc gene under regulation of the SV40 early region promoter and the antibiotic resistance plasmid pSV2neo. Transfectant cell lines expressing up to 4-fold higher total GST activity than in the parental wild type cell line were identified. Southern blot analysis confirmed a DNA fragment corresponding in size to the transfected GST Yc complementary DNA. Wild type MatB cells contain very low levels of Yc protein, whereas the Yc+ clones showed greatly increased amounts of the Yc subunit. The effect of increased GST Yc activity on the sensitivity of the transfected clones to various cytotoxic agents was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell survival assay. The clones expressing recombinant GST Yc were more resistant to melphalan (6- to 12-fold), mechlorethamine (10- to 16-fold), and chlorambucil (7- to 30-fold). In late passage populations of the GST Yc+ clones that had been grown over a period of 14 months under continuous selection in G418, GST activity was decreased and it was paralleled by a decrease in Yc protein. These late passage clones with diminished GST Yc content also demonstrate a partial reversion toward the wild type phenotype as determined by cytotoxicity assays using melphalan, mustargen, and chlorambucil. Interstrand DNA cross-links induced by mechlorethamine were significantly lower at 0, 2, and 20 h posttreatment in one of the GST Yc+ clones when compared to wild type MatB cells. These studies indicate that GST Yc overexpression can confer resistance to alkylating agents and that this correlates with inhibition of DNA cross-link formation.

Alkylating Agents↗
PubMed1992

Drug resistance in cultured rat liver epithelial cells spontaneously and chemically transformed.

Cultured rat liver epithelial cells (RLE) transformed with repeated treatments of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) demonstrate many features of the common biochemical phenotype of multidrug resistance (MDR) seen in vivo in 'resistant hepatocytes'. The cells have increased glutathione-S-transferase placental subunit (GST-Yp), gamma-glutamyltranspeptidase (GGT), glutathione (GSH) and glutathione peroxidase and are resistant to MNNG. Phenotypically identical RLE cells spontaneously transformed by selective culture conditions showed low levels of GGT and GST and were not resistant to MNNG. Both chemical and spontaneous transformants are cross resistant to doxorubicin although resistance is consistently greater in chemical transformants. No direct correlation was found between the degree of resistance to doxorubicin and MDR gene expression in either of the chemically or spontaneously transformed RLE cells. These observations suggest that in chemical carcinogenesis, other mechanisms of drug detoxification are involved and that MDR expression is not a consistent feature.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

In vivo and in vitro mechanisms of drug resistance in a rat mammary carcinoma model.

Many in vitro tumor models have been examined to help understand the precise mechanisms responsible for drug resistance. The importance of these results in vivo remains uncertain. MatB 13762 is a rat mammary adenocarcinoma cell line that can be grown both in vitro and as a solid tumor in Fischer 344 rats, thus permitting the examination of tumor cell drug resistance under both conditions. Two cell lines have been selected in vitro for resistance to Adriamycin (AdrR) and melphalan (MlnR), respectively. Each subline has the following features: AdrR, increased mdr-1 messenger RNA, a high level of cross-resistance to vincristine and atypical low level resistance to melphalan and 1,3-bis(2-chloroethyl)-1-nitrosourea, decreased cellular glutathione content, and increased expression of Yc and Yp glutathione S-transferase isozymes; MlnR, low level drug resistance to melphalan and cross-resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea, Adriamycin, and vincristine; increased cellular concentration of glutathione; elevated glutathione S-transferase activity; and greatly increased messenger RNA specific to the Yc and Yp glutathione-S-transferase subunits. Most of the biochemical and molecular features described above are present but significantly less prominent in tumors grown in vivo. This model provides the opportunity to examine the magnitude of expression and the clinical significance of in vitro resistance in an in vivo model.

Animals↗
PubMed1991

Glutathione depletion in human and in rat multi-drug resistant breast cancer cell lines.

The effects of GSH depletion in a human breast cancer cell line and a multi-drug resistant subline (ADRr) were determined in a number of experimental conditions. The ADRr cells contained lower GSH concentration which cannot be explained solely on the basis of differences in cell kinetics, and yet the rate-limiting synthetic enzyme gamma-glutamylcysteine synthetase was increased 2-fold. Inhibition of GSH synthesis by BSO resulted in more rapid and more pronounced GSH depletion in ADRr compared to the wild-type cells, suggesting that enhanced GSH utilization and efflux in the resistant cells account for the lowered basal concentration. In addition, the gamma-glutamyl moiety salvage enzyme gamma-glutamyltranspeptidase was reduced markedly in the ADRr cell line. Since these cells have overexpression of the efflux pump protein P-glycoprotein, we examined the effects on cellular GSH of inhibition of the pump's function by verapamil. We found that verapamil significantly depleted cellular GSH. In a rat mammary carcinoma cell line selected in Adriamycin for multi-drug resistance, a similar molecular phenotype has been described including diminished cellular GSH concentration. Verapamil treatment of these cells also resulted in significant depletion of cellular GSH. These results are consistent with the recent report that combined treatment of BSO and verapamil has an additive effect on cytotoxicity. It is likely that decreased basal GSH concentration is due to oxidation and conjugation of it in reactions catalyzed by the enhanced peroxidase and GST found in these cells.

Animals↗
PubMed1991

Effect of proliferative state on glutathione S-transferase isoenzyme expression in cultured rat liver epithelial cells.

A specific biochemical phenotype is expressed during chemical hepatocarcinogenesis, which includes increased activity of the various isoenzyme forms of glutathione S-transferase (GST) composed of class alpha (Ya/Yc), class mu (Yb) and class pi (Yp) gene products. In vitro cell lines of normal and chemically transformed rat liver epithelial cells provide an opportunity to examine the regulation of expression of GST isoenzymes. We have studied the effect of the state of proliferation in culture on both the enzymic activity and the isoenzyme-specific mRNA expression. In normal rat liver epithelial cells (WB-F344), basal expression of the Yp subunit decreases, and of the Yb subunit increases, in cells at confluence compared with those in logarithmic-phase growth. In a subline of WB-F344 cells that has been chemically treated in vitro (GN6), there was greater Yp expression; however, the effect of growth status on both subunits was the same as in the nontransformed WB-344 cells, and the Ya subunit was not expressed. Inhibition of RNA synthesis with actinomycin D was limited, demonstrating pronged half-lives of the GST mRNAs, and shows a slightly greater decrease in GST-Yp specific mRNA levels in the confluent cells. Also nuclear run-off experiments demonstrate identical transcription rate in confluent and pre-confluent cells. These data suggest that the increase in Yp steady-state RNA in preconfluent cells is due to increased stability of the GST-Yp mRNA. In tumor cells derived from GN6 cells, the regulatory effects of growth status on the Yb and Yp expressions were absent. However, in these cells Ya subunit was expressed and this was subject to the effects of cell proliferation. We conclude that the growth status of cells in culture exerts a significant regulatory control on the GST isoenzyme gene expression. The effects are probably mediated at independent regulatory sites in each gene. The state of transformation of rat liver epithelial cells may determine responsiveness to this effect.

Animals↗
PubMed1990

Expression of transforming growth factor-alpha in primary human colon and lung carcinomas.

The expression of TGF-alpha in human colon and lung carcinoma cell lines has been reported previously, but its expression in primary tumours has not been described in detail. We have used the radio-immunoassay method to measure the specific content of immunoreactive TGF-alpha in the acid ethanol extracts of normal and cancerous tissues of human colon and lung. The average TGF-alpha content of colon carcinomas is 4 times that of the normal mucosa, and for non-small cell lung carcinomas it is twice that of the normal parenchyma. Because of variability in the TGF-alpha expression among individuals and in different segments of colon and lobes of lung, the ratio of TGF-alpha content of paired tumour and normal tissue was also calculated. On average, the tumour/normal ratio for colon carcinoma is higher than that for lung carcinoma. Although 55% of colon tumours show a ratio 4 times, or greater, only 33% of lung carcinomas demonstrate this ratio. The level of TGF-alpha in both colon and lung carcinomas does not correlate with histological type stage, grade nor degree of desmoplasia of these tumours. Northern blot analysis of total cellular RNA confirms the expression of an approximately 4.8 kb TGF-alpha mRNA in normal colonic mucosa and lung parenchyma. However, in contrast to the results of radio-immunoassay, significant over-expression of TGF-alpha mRNA is uncommon in primary human colon carcinomas.

Blotting, Northern↗
PubMed1985

Nosocomial legionellosis in surgical patients with head-and-neck cancer: implications for epidemiological reservoir and mode of transmission.

A prospective pneumonia study was conducted simultaneously on head-and-neck surgery wards at two hospitals over 2 years; one hospital had a water supply contaminated with Legionella pneumophila but no record of having had a case of legionella pneumonia, and the other had just decontaminated its water supply because of known endemic nosocomial legionellosis. Special laboratory tests for legionella were done on all cases of nosocomial pneumonia irrespective of clinical impression. Over the first 18 months, the rate of nosocomial legionellosis was 30% at the first hospital and 0% at the second. Patients who underwent laryngectomy did not acquire the disease. Hyperchlorination at the first hospital was followed by a fall (p less than 0.01) in legionella pneumonias. Thus legionella pneumonias can be overlooked if special laboratory tests are not applied routinely, and surgical patients with head-and-neck cancer may be at high risk of nosocomial legionellosis because of the potential for pulmonary aspiration of contaminated water or orophyaryngeal microflora and/or frequent manipulation of the respiratory tract. This study demonstrates the benefits of examining the environment for legionella despite the absence of documented disease.

Chlorine↗