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Biomedical subjects

N K Lee

Publications and source records attributed to N K Lee.

13 recordsLinked to original sources

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

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

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

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

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

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

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

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

Tumor suppressor genes.

Tumor suppressor genes are negative regulators of cell growth. When their normal function is compromised, absence of their inhibitory effects can lead to unrestrained cell cycling and growth. Strong evidence now confirms that loss of proper function of these genes is a common occurrence leading to cancer. Their failure can be caused by alterations in the gene DNA or malfunction of their protein products. The recent extraordinary accumulation of knowledge about these genes reveals that normal carcinogenesis represents breakdown of normal regulatory processes.

Cell Transformation, Neoplastic