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Biomedical subjects

N K Lee

Publications and source records attributed to N K Lee.

At least 37 records · Page 2Linked to original sources
PubMed1994

Allelic loss at chromosomes 3p, 8p, 13q, and 17p associated with poor prognosis in head and neck cancer.

BACKGROUND: Little is known about the molecular genetic events that contribute to the pathogenesis of squamous cell carcinoma of the upper aerodigestive tract. Previous molecular genetic studies have been limited to the identification of mutations of the p53 (also known as TP53) tumor suppressor gene, activation of a limited set of oncogenes, allelic loss at 3p and other locations, and occasional association with human papillomavirus infection. PURPOSE: Our purpose was to screen tumor tissue and blood from patients with squamous cell carcinoma of the upper aerodigestive tract for loss of heterozygosity at polymorphic loci corresponding to each of the autosomal chromosomes and to identify the locations of additional putative tumor suppressor genes, other than RB (also known as RB1) and p53, that may contribute to the pathogenesis of this disease. METHODS: Tumor tissue and blood were obtained from 68 consecutive patients with squamous cell carcinoma of the upper aerodigestive tract. In all cases, tumor tissue was obtained from the center of the surgical specimen. The relative absence of non-neoplastic tissue was confirmed by frozen-section histologic examination of immediately adjacent tissue. Initially, 30 paired tissue and blood samples were tested for loss of heterozygosity by polymerase chain reaction (PCR) to amplify 43 different highly polymorphic sequences containing small oligonucleotide repeats. After PCR amplification, with unique oligonucleotides flanking the repeat, visualization and sizing of the alleles on DNA sequencing gels were performed. Specific loss of heterozygosity was distinguished from random genetic loss due to generalized chromosomal instability if it occurred in more than 20% of specimens tested for a particular marker. RESULTS: Significant loss of heterozygosity (> 20%) occurred at alleles at chromosome bands 3p21 (32%), 3p25-26 (56%), 8pter-21.1 (31%), 13q14 (27%), and 17p12 (45%). Loss of heterozygosity at more than two loci was significant with a poor prognosis (P = .039). CONCLUSIONS: These findings demonstrate that squamous cell carcinoma of the upper aerodigestive tract exhibits genetic alterations at multiple loci and that allelic loss at more than two locations is indicative of a poor prognosis (the likelihood of the patient dying of disease). IMPLICATIONS: While tumor suppressor genes at 3p (VHL), 13q (RB), and 17p (p53) have been identified, altered genes at other loci on 3p and on 8p have not yet been characterized. Furthermore, the genotype at these loci for squamous cell carcinoma of the upper aerodigestive tract has prognostic importance and may identify the patients who should receive the most aggressive treatment.

Adult↗
PubMed1994

Endoscopic resection of the intranasal frontal sinus floor.

The current accepted treatment for chronic frontal sinus disease unresponsive to medical management and endoscopic surgery is an external approach to either obliterate the sinus or restore communication to the nasal cavity. Here reported is an endoscopic approach for resection of the intranasal frontal sinus floor, a modification of a procedure first described by Lothrop in 1899. Eleven patients underwent this operation from April 1993 to December 1993. One complication, a cerebrospinal fluid leak treated successfully endoscopically, has occurred. Of the 7 patients followed up 3 months or longer after surgery, only 1 has developed symptoms of recurrent frontal sinusitis. On the basis of this limited preliminary experience, the endoscopic Lothrop procedure shows promise as an effective operation designed to establish a physiologic communication between the frontal sinus and the nasal cavity in selected patients who would otherwise be candidates for an external approach.

Adolescent↗
PubMed1993

p53, retinoblastoma, and human papillomavirus in squamous cell carcinoma and adjacent normal mucosa of the upper aerodigestive tract.

OBJECTIVE: The primary objective of this study was to determine the incidence of p53 and retinoblastoma tumor suppressor gene mutations and human papillomavirus infection in squamous cell carcinoma and adjacent normal mucosa of the upper aerodigestive tract. The secondary objective was to associate these findings with clinical and histopathologic features. DESIGN: Point mutations of p53 were identified by single-strand conformation polymorphism analysis and confirmed by direct DNA sequence analysis. Polymerase chain reaction-based methods were used to identify loss of heterozygosity of the retinoblastoma tumor suppressor gene and the presence of human papillomavirus sequences. SETTING: University-based tertiary care center. PATIENTS OR OTHER PARTICIPANTS: Forty-five consecutive cases of upper aerodigestive tract squamous cell carcinoma. RESULTS: Eleven point mutations of p53 were identified in tumor samples (24%). No functional p53 mutations were detected in adjacent normal tissue from eight of these individuals nor was there evidence of p53 alteration in normal tissue adjacent to 12 of 30 additional tumors tested that demonstrated conformational alterations by single-strand conformation polymorphism analysis. The p53 mutations were significantly associated with local invasion. Loss of heterozygosity (which has a 20% chance of random occurrence in tumors) was detected at the retinoblastoma locus in 15% of the tumors tested. Five of the specimens (11%) were positive for human papillomavirus sequences (two of which also contained p53 mutations). CONCLUSIONS: These findings suggest that p53 but not retinoblastoma or human papillomavirus is an important prognostic factor and is involved as a late event in the pathogenesis of upper aerodigestive tract squamous cell carcinoma.

Base Sequence↗
PubMed1993

The importance of alcohol expectancies and drinking refusal self-efficacy in the quantity and frequency of alcohol consumption.

Expectancies about alcohol have been shown to be related to and predictive of alcohol consumption. Research to date, however, has often failed to make a clear distinction between expectations about the effects of alcohol (alcohol expectancies) and expectations about one's ability to resist drinking in certain situations (drinking refusal self-efficacy). There is some evidence that alcohol expectancies (AE) and drinking refusal self-efficacy (DRSE) can play differential roles in the prediction of consumption in terms of quantity and frequency of drinking. This study aimed to replicate and extend these findings to the community population. Subjects (N = 185) were recruited from the general community using a peer network system. They were given a booklet comprising six self-report measures, including the Drinking Expectancy Questionnaire (DEQ), the Drinking Self-Efficacy Questionnaire (DSEQ), and the Khavari Alcohol Test (KAT), which produces measures of usual and maximum quantity as well as frequency of the usual and maximum consumed. It was expected that AE would be related to frequency of consumption whereas DRSE would be related to both quantity and frequency. The findings confirmed the differential role of AE and DRSE in drinking, and the role of factors within the two concepts. Results indicated that low DRSE was related to higher frequency of general consumption and a larger maximum quantity on any one occasion. AE was related to frequency, but not to quantity, as expected. The findings are presented with respect to the theoretical constructs; clinical and research implications are also discussed.

Adolescent↗
PubMed1993

Splenic and partial hepatic necrosis after vascular occlusion.

A 74-year-old woman underwent two operations to correct an aortoduodenal fistula and to have an axillofemoral bypass graft inserted; these required temporary vascular occlusion. Her hepatic function test results began deteriorating. Initial and follow-up Tc-99m sulfur colloid studies revealed activity in the kidneys, consistent with disseminated intravascular coagulation. There was significant radiocolloid in the bone marrow and lungs, suggesting severe hepatic dysfunction. The spleen was not demonstrable on dynamic images or static views. In addition, there was a significant lateral hepatic defect, with a "lung overlap." The splenic lack of function and the hepatic lesion were due to necrosis (demonstrable on CT imaging), likely related to the prior vascular clamping.

Abdomen↗
PubMed1992

Inositol trisphosphate (InsP3) causes contraction in skeletal muscle only under artificial conditions: evidence that Ca2+ release can result from depolarization of T-tubules.

It has been proposed that in striated muscle inositol 1,4,5-trisphosphate (InsP3) may serve as a chemical transmitter linking membrane depolarization to Ca(2+)-release from the sarcoplasmic reticulum. Key to that hypothesis of excitation-concentration (EC) coupling was the observation that skinned muscle fibres contract on the application of InsP3. Yet skinned fibres do not always respond in this way, and in our hands intact fibres do not contract when InsP3 (1 microM-1 mM) is microinjected into them. Glycerol-shocked fibres do contract, however, and so do intact fibres that have been depolarized to about -50 mV by increasing [K+]0. These observations and related pharmacological evidence support the hypothesis that InsP3 causes a low-level depolarizing current to cross the T-tubular membrane. This current is sufficient to depolarize the T-tubules to the threshold for contraction only when the tubules are sealed over or when they are already close to the threshold. The InsP3-induced Ca2+ release sometimes observed in skinned muscle fibres and in vesicles derived from junctional sarcoplasmic reticulum probably often results from an action on sealed-over transverse tubules; in such situations it is an artifact of cell disruption. The fact that high concentrations of InsP3 do not cause contraction in normal muscle fibres is strong evidence against the hypothesis that InsP3 plays a central role in EC coupling in skeletal muscle.

Aequorin↗
PubMed1992

Ventilation-perfusion lung imaging in nitrofurantoin-related pulmonary reaction.

A woman with a history of multiple drug allergies was admitted for cough and dyspnea. She had been taking nitrofurantoin for 10 days, was febrile, and had a rash on the trunk and extremities. A chest radiograph revealed right-sided pleural effusion and basal markings. Because of suspected nitrofurantoin-related pulmonary reaction, the medication was discontinued and the patient was started on an H2-blocker and intravenous corticosteroids. She improved clinically, and within 24 hours a radiograph revealed that her chest had largely cleared. Restricted distribution of radioxenon, seen initially on a ventilation lung scan, also reverted to near normal by the follow-up. The first perfusion lung scan showed multiple but nonspecific changes; this also came back to near normal. The nitrofurantoin-related pulmonary reaction should be considered in patients who present with pulmonary signs/symptoms while on the medication.

Drug Hypersensitivity↗
PubMed1991

Metastatic adenocarcinoma to the neck from an unknown primary source.

We report a retrospective review of 223 patients who presented to the Department of Head and Neck Surgery from 1970 through 1987 with a diagnosis of metastatic adenocarcinoma of unknown primary origin. Multivariate analysis was performed using the following parameters: age, sex, initial side and site of nodal involvement, involvement of other body sites, degree of differentiation, treatment modality, outcome, and survival. Follow-up was obtained in all patients, with a minimum of 2 years for survivors. Average age was 55 years, with an approximately equal male:female ratio. The most common site of presentation was the supraclavicular fossa (76%). The initial side of presentation was the left neck in 53% of patients, right neck in 33%, and bilateral in 14%. Metastatic disease to other body sites was present in 86% of patients, with the most common sites being mediastinum (35%), lung (21%), and bones (19%). Increased survival was associated with unilateral neck involvement (p = 0.001) and disease limited to nodes above the cricoid cartilage (p = 0.007). Mean survival was 17 months, with a median of 8 months. Death was due to the index cancer in all but four patients; three of these four patients died of treatment-related causes. Survival was 20% at 2 years and 9% at 5 years. Length of survival was not affected by age, sex, initial side of neck disease, location of other metastatic sites, histologic appearance, or treatment modality. Our current algorithm for the work-up and treatment of this lethal disease is explained.

Adenocarcinoma↗
PubMed1991

Marine natural products. XXVI. Biologically active tridecapeptide lactones from the Okinawan marine sponge Theonella swinhoei (Theonellidae). (2). Structures of theonellapeptolides Ia, Ib, Ic, and Ie.

Five tridecapeptide lactones, named theonellapeptolides Ia (1), Ib (2), Ic (3), Id (4), and Ie (5), were isolated from the Okinawan marine sponge Theonella swinhoei. Following the structure elucidation of theonellapeptolide Id (4), the structures of theonellapeptolides Ia (1), Ib (2), Ic (3), and Ie (5) were determined on the basis of chemical and physicochemical evidence including high performance liquid chromatography and circular dichroism combined analysis of the amino acid compositions. Theonellapeptolides Ib (2), Ic (3), Id (4), and Ie (5) exhibit moderate cytotoxic activity towards for L1210 in vitro (IC50 1.6, 1.3, 2.4, and 1.4 micrograms/ml, respectively), and theonellapeptolide Ie (5) exhibits ion-transport activities for Na+ and K+ ions.

Amino Acid Sequence↗
PubMed1990

Supraglottic laryngectomy for intermediate-stage cancer: U.T. M.D. Anderson Cancer Center experience with combined therapy.

We reviewed the records of all patients with previously untreated squamous cell carcinomas of the supraglottic larynx who presented to The University of Texas M.D. Anderson Cancer Center from 1974 to 1987. Of 404 patients, 60 (15%) underwent supraglottic laryngectomy and functional anterior neck dissection as a primary modality of therapy; these patients were studied. Fifty of the 60 patients (83%) received adjunctive postoperative radiotherapy. Tumor-free survival was 96% at 2 years and 91% at 5 years. There were no local failures, 4 regional failures, and 3 distant metastases. Second cancers, mostly of the lung, occurred in 9 patients (15%). Three patients required completion laryngectomies for intractable aspiration. Analysis of deglutition and tracheal decannulation rehabilitation revealed a higher incidence of complications in patients who underwent arytenoidectomies.

Algorithms↗
PubMed1988

Head and neck squamous cell carcinomas associated with human papillomaviruses and an increased incidence of cervical pathology.

Human papillomaviruses (HPVs) have been identified in benign and cancerous epithelial lesions of the female genital tract. They have also been identified in papillomata and cancers of the upper aerodigestive tract. This study investigates the hypothesis that lesions of the cervicovaginal area are more common in women with cancers of the head and neck region. The presence of HPV in lesions of both regions is examined. Seven female patients with cancer of the upper aerodigestive tract had DNA analysis of their carcinoma specimens. HPV type 16 was found in two of the seven (28%). Fourteen female patients with upper aerodigestive tract cancers had Papanicolaou smears to search for cytologic evidence of HPV infection, and cervicovaginal lavages to analyze DNA from exfoliated cervical cells. Five of thirteen (38%) Papanicolaou smears revealed koilocytotic atypia and three of these patients had HPV DNA types 16 or 18 identified in the cervical lavage. The incidence of cervical atypia noted is 13-fold greater than average. One patient had HPV type 16 in both her supraglottic cancer and in her cervicovaginal lavage. Evidence of HPV infection at two separate anatomic sites suggests a systemic susceptibility to HPV infection.

Carcinoma, Squamous Cell↗
PubMed1983

Active shortening retards the decline of the intracellular calcium transient in mammalian heart muscle.

When active shortening of the cat papillary muscle was allowed at any time during a contraction, the intracellular concentration of free calcium ions, detected with the calcium-sensitive bioluminescent protein aequorin, was higher than at comparable times in isometric twitches. The difference was not attributable to the differences of length involved or to motion artifacts, and must have been related to the act of shortening or the difference in force development in the two types of contractions. This observation and the phenomenon of shortening deactivation are both consistent with the hypothesis that attachment of cross bridges increases the affinity of the myofilaments for calcium ions.

Aequorin↗
PubMedDate not supplied

Molecular biology: the polymerase chain reaction.

Upper aerodigestive tract (UADT) cancers provide an excellent carcinogenesis model for a number of reasons: they are accessible to observation, are usually associated with a known environmental carcinogen (tobacco by-products), are sometimes associated with a tumorigenic DNA virus (HPV), and fall along a spectrum of progressive disease from normal mucosa through leukoplakia and verrucous carcinoma to invasive and metastatic carcinoma. Despite the presence of this unique model, the field of head and neck oncology, as a whole, has been slow in establishing an efficient 2-way conduit between the bedside and the laboratory. Such open communication is important as current evidence suggests that future staging and therapy of head and neck tumors will depend not only on familiar macroscopic and light microscopic criteria, but also on factors that are currently identifiable only in the basic science laboratory. To have a significant impact on the direction and relevance of basic research, clinicians should become knowledgeable and conversant in the vocabulary and general concepts of basic science. The goal of this section is to facilitate communication between the basic researcher and the clinician, thereby promoting clinically relevant basic research. This is to be achieved by fostering understanding of the power, limitations, scope, and horizons of current basic research concepts and techniques. Subsequent articles will review current research topics germane to head and neck cancer, such as oncogenes and tumor suppressor genes, mechanisms of metastasis, tumor immunology and its modulation, and virology.

Head and Neck Neoplasms↗
PubMedDate not supplied

Oncogenes.

We have discussed oncogenes and their protein products which act at various sites in tumor cells, with special consideration for tumors of the head and neck. In a few systems studied, application of this knowledge has led to preliminary therapeutic interventions. While abnormal expression and function of these genes and proteins are responsible for transformation to the malignant phenotype, further study of these oncogenes will also help illuminate the mechanisms of normal cellular growth and differentiation. Although cancers of the upper aerodigestive tract are heterogeneous in origin and the multi-step process of carcinogenesis is likely to vary in different tumors, the head and neck tumor spectrum is a good model for tumorigenesis and should provide valuable insight into general carcinogenesis and normal cellular growth controls.

Cell Transformation, Neoplastic↗