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Biomedical subjects

J E Lewis

Publications and source records attributed to J E Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1999

Intranasal verrucous carcinoma: relationship to inverting papilloma and human papillomavirus.

OBJECTIVES: To establish the incidence, appearance, behavior, and appropriate treatment of intranasal verrucous carcinoma and determine its relationship to inverting papilloma and human papillomavirus (HPV). STUDY DESIGN: Retrospective review of all cases of intranasal verrucous carcinoma seen at the Mayo Clinic from 1960 through May 1996. METHODS: Retrospective chart review and data collection for age, sex, smoking history, location, association with inverting papilloma, treatment, recurrence, and follow-up. Polymerase chain reaction (PCR) testing for the presence of HPV DNA was performed on all specimens. RESULTS: Of the 13 patients identified, most presented with nasal obstruction (10) or a noticeable intranasal lesion (8). The maxillary sinus was the extranasal site most often involved. Five patients had verrucous cancer develop in an inverting papilloma, and one had squamous cell carcinoma with the verrucous component (a hybrid tumor). All but one patient underwent surgery as initial treatment; only one patient had preoperative radiation therapy. Surgical procedures ranged from local excision to a craniofacial resection. Follow-up ranged from 2 months to 32 years (mean, 6.5 y). Four patients had a single recurrence and two tumors recurred a second time. No metastases developed and no one died from the tumor. In seven patients (10 specimens), DNA was successfully amplified for PCR testing, and no HPV DNA was detected. CONCLUSIONS: When verrucous tumors are discovered early, they can be treated effectively with wide local excision. In some cases, a more extensive procedure may be required. A possible role for HPV in the etiology of these tumors was not found.

Adult↗
PubMed1998

Quantitative analysis of a directed behavior in the medicinal leech: implications for organizing motor output.

The local bend is a directed behavior produced by the leech, Hirudo medicinalis, in response to a light touch. Contraction of longitudinal muscles near the touched location results in a bend directed away from the stimulus. We quantify the relationship between the location of touch around the body perimeter and the behavioral output by using video analysis, muscle tension measurements, and electromyography. On average, the direction of the behavioral output differed from the touch location by <8% of the total body perimeter. We discuss our results in the context of two contrasting behavioral strategies: a Continuous strategy, in which the local bend is directed exactly opposite to stimulus location, and a Categorical strategy, in which there are four distinct bend directions, each elicited by stimuli given in a single quadrant of the body perimeter. To distinguish between these strategies, we delivered two competing stimuli simultaneously. The resulting behavioral output is best described by an average of the effects of each stimulus given alone and thus provides support for the Continuous strategy. We also use a simple model, based on anatomical and physiological data, to predict the responses of the known motor neurons to different stimulus locations. The model shows that the activation of two of the motor neurons (D and V) is inconsistent with a Categorical strategy. However, these neurons are known to be active during the local bend behavior. This result, along with our experimental observations, suggests that the local bend network uses a Continuous strategy to encode stimulus location and produce directed behavioral output.

Animals↗
PubMed1998

Combined neck dissection and postoperative radiation therapy in the management of the high-risk neck: a matched-pair analysis.

PURPOSE: The purpose of this study was to determine the efficacy of postoperative adjuvant radiation therapy with regard to reducing the rate of recurrence in the neck, cancer-related death, and death from any cause in patients with squamous cell carcinoma of the head and neck region metastatic to neck nodes. METHODS: This was a retrospective review of patients with pathologically confirmed nodal metastases who underwent neck dissection and postoperative adjuvant radiation therapy for squamous cell carcinoma of the head and neck region. Time to recurrence in the dissected area of the neck, any recurrence in the neck, cancer-related death, and death from any cause were estimated with the Kaplan-Meier method. A matched-pair analysis was performed utilizing a cohort of patients who underwent neck dissection without postoperative radiation therapy. The patients from the two cohorts were matched according to previously reported high-risk features for cancer recurrence and death. Cox hazards models for the matched pairs were used to evaluate the relative risk of subsequent recurrence in the dissected side of the neck, any neck recurrence, cancer-related death, and overall survival. MATERIALS: The medical records and pathologic slides of 95 consecutive patients with pathologically confirmed nodal metastases from squamous cell carcinoma of the head and neck region who underwent neck dissection and postoperative adjuvant radiation therapy between January 1974 and December 1990 were reviewed. Previously published data from 284 patients with squamous cell carcinoma of the head and neck region treated with neck dissection alone between January 1970 and December 1980 were used for a matched-pair analysis. RESULTS: The relative risks for recurrence in the dissected side of the neck, any neck recurrence (dissected neck or delayed undissected neck metastasis), cancer-related death, and death from any cause for patients treated with operation alone relative to those treated with operation and postoperative radiation were 5.82, 4.72, 2.21, and 1.67, respectively. CONCLUSION: This study provides evidence that postoperative adjuvant radiation therapy for the high-risk neck can reduce the rate of recurrence within a dissected neck, delayed metastasis within an undissected neck, cancer-related death, and death from any cause.

Adult↗
PubMed1998

A neuronal network for computing population vectors in the leech.

The correlation of neuronal activity with sensory input and behavioural output has revealed that information is often encoded in the activity of many neurons across a population, that is, a neural population code is used. The possible algorithms that downstream networks use to read out this population code have been studied by manipulating the activity of a few neurons in a population. We have used this approach to study population coding in a small network underlying the leech local bend, a body bend directed away from a touch stimulus. Because of the small size of this network we are able to monitor and manipulate the complete set of sensory inputs to the network. We show here that the population vector formed by the spike counts of the active mechanosensory neurons is well correlated with bend direction. A model based on the known connectivity of the identified neurons in the local bend network can account for our experimental results, and is suitable for reading out the neural population vector. Thus, for the first time to our knowledge, it is possible to link a proposed algorithm for neural population coding with synaptic and network mechanisms in an experimental system.

Action Potentials↗
PubMed1998

Verrucous carcinoma of the larynx: a review of 53 patients.

BACKGROUND: Verrucous carcinoma of the larynx is a rare laryngeal neoplasm that can be confused with a benign process. Although usually curable at an early stage, it can be locally aggressive if left untreated. We describe our experience with this tumor and make recommendations for diagnosis and treatment. METHODS: From 1960 through 1990, 53 patients received initial treatment for verrucous carcinoma of the larynx at the Mayo Clinic. We retrospectively reviewed the presentation, diagnosis, treatment, and outcomes in these patients. All cases were confirmed by histologic examination. RESULTS: All but two patients were men, and most were smokers. Most tumors were found in the glottis, and 72% were T1 lesions at presentation. Six patients had hybrid tumors consisting of conventional squamous cell carcinoma along with the verrucous component. Sixteen patients had lesions that had been diagnosed as benign before they were seen at our institution. Treatment ranged from transoral excision to laryngopharyngectomy. Ten patients experienced recurrence, but only two patients died of the tumor. No pure verrucous lesion metastasized, and overall survival was similar to that of an age- and sex-matched cohort from the Western North Central U.S. white population. CONCLUSIONS: When discovered early, verrucous carcinoma of the larynx can be treated by local excision with good results; extensive lesions, however, may require more-aggressive procedures. Close communication between the pathologist and the clinician as well as adequate biopsy is essential for diagnosis. Patients with a conventional squamous cell carcinoma coexistent with a verrucous lesion must be treated as if they had invasive squamous cell carcinoma.

Adult↗
PubMed1998

Chemotherapy for advanced esthesioneuroblastoma: the Mayo Clinic experience.

OBJECTIVE: Esthesioneuroblastoma (olfactory neuroblastoma) is a rare neuroendocrine tumor that arises in the upper nasal cavity from the olfactory epithelium. Little information is available regarding the treatment of these tumors with chemotherapy in the advanced setting. A retrospective review of patients with recurrent esthesioneuroblastoma treated with chemotherapy between 1970 and 1995 at the Mayo Clinic was undertaken to gain more information regarding the efficacy of chemotherapy treatment for these patients. METHODS: Ten patients were identified using a computerized data base available at this institution. The clinical and pathological materials, when available, were reviewed, and each tumor reviewed was assigned a Hyams' grade. RESULTS: There were six men and four women, ranging in age from 22 to 74 years, all of whom had assessable Kadish Stage C disease at the time of chemotherapy treatment. The chemotherapy regimens and clinical follow-up varied during this 25-year time span. The only tumor regression resultant from chemotherapy was observed in patients with high-grade tumors. Two of four patients with high-grade tumors obtained regression from first-line, platinum-based chemotherapy, with a mean duration of regression of 9.3 months (range, 2-13 mo). Survival time from initial diagnosis was 139.5 months (range, 83-168 mo) in patients with low-grade tumors and 32.2 months (range, 5-84 mo) in patients with high-grade tumors. Survival from initial chemotherapy treatment was 44.5 months (range, 3-130 mo) in patients with low-grade tumors and 26.5 months (range, 2-67 mo) in patients with high-grade tumors. CONCLUSION: Hyams' grading of esthesioneuroblastoma tumors seems to be important in predicting response to chemotherapy. Despite sensitivity to platinum-based chemotherapy, patients with high-grade tumors in this series had a much more aggressive course than did those with lower-grade tumors. This series suggests that cisplatin-based chemotherapy is active in advanced, high-grade esthesioneuroblastoma and is a reasonable choice in the systemic treatment of these patients.

Adult↗
PubMed1998

Use of antipsychotic drugs in nursing homes: current compliance with OBRA regulations.

OBJECTIVE: To examine the degree and patterns of compliance with the Omnibus Budget Reconciliation Act (OBRA) regulations regarding the use of antipsychotic drugs in nursing homes. DESIGN: Retrospective chart review of all resident records. PARTICIPANTS: Eight nursing homes: five community, two county-owned, and one university-affiliated Veterans Administration facility. MEASUREMENTS: A structured assessment instrument to track compliance with each aspect of the OBRA regulations regarding antipsychotic drug use. RESULTS: A total of 1573 nursing home residents' pharmacy records were reviewed between August 1994 and March 1996. Two hundred seventy-nine residents were actively taking antipsychotic medications (prevalence = 17.7%). Mean compliance greater than 70% was found for (1) appropriate diagnostic indication (mean = 70.9%), (2) dosage within recommended limits (mean = 90.1%), and 3) documented appropriate target symptoms (mean = 90.4%). Dosages were more likely to exceed limits in those patients with histories of major mental illness, particularly schizophrenia. CONCLUSIONS: Nursing homes were better able to comply with those guidelines that are most specific. Educational interventions now need to focus on behavioral interventions, monitoring of adverse effects, and efficacy. These data are useful in establishing threshold levels of performance and can be used by nursing homes for continuous quality improvement. OBRA continues to impact neuroleptic drug prescribing practices in nursing homes significantly.

Aged↗
PubMed1998

Representation of touch location by a population of leech sensory neurons.

To form accurate representations of the world, sensory systems must accurately encode stimuli in the spike trains of populations of neurons. The nature of such neuronal population codes is beginning to be understood. We characterize the entire sensory system underlying a simple withdrawal reflex in the leech, a bend directed away from the site of a light touch. Our studies show that two different populations of mechanosensory neurons each encode touch information with an accuracy that can more than account for the behavioral output. However, we found that only one of the populations, the P cells, is important for the behavior. The sensory representation of touch location is based on the spike counts in all of the four P cells. Further, fewer than three action potentials in the P cell population, occurring during the first 100 ms of a touch stimulus, may be required to process touch location information to produce the appropriately directed bend.

Action Potentials↗
PubMed1997

Cross-talk between adherens junctions and desmosomes depends on plakoglobin.

Squamous epithelial cells have both adherens junctions and desmosomes. The ability of these cells to organize the desmosomal proteins into a functional structure depends upon their ability first to organize an adherens junction. Since the adherens junction and the desmosome are separate structures with different molecular make up, it is not immediately obvious why formation of an adherens junction is a prerequisite for the formation of a desmosome. The adherens junction is composed of a transmembrane classical cadherin (E-cadherin and/or P-cadherin in squamous epithelial cells) linked to either beta-catenin or plakoglobin, which is linked to alpha-catenin, which is linked to the actin cytoskeleton. The desmosome is composed of transmembrane proteins of the broad cadherin family (desmogleins and desmocollins) that are linked to the intermediate filament cytoskeleton, presumably through plakoglobin and desmoplakin. To begin to study the role of adherens junctions in the assembly of desmosomes, we produced an epithelial cell line that does not express classical cadherins and hence is unable to organize desmosomes, even though it retains the requisite desmosomal components. Transfection of E-cadherin and/or P-cadherin into this cell line did not restore the ability to organize desmosomes; however, overexpression of plakoglobin, along with E-cadherin, did permit desmosome organization. These data suggest that plakoglobin, which is the only known common component to both adherens junctions and desmosomes, must be linked to E-cadherin in the adherens junction before the cell can begin to assemble desmosomal components at regions of cell-cell contact. Although adherens junctions can form in the absence of plakoglobin, making use only of beta-catenin, such junctions cannot support the formation of desmosomes. Thus, we speculate that plakoglobin plays a signaling role in desmosome organization.

Cadherins↗
PubMed1997

Cell cycle regulation of the human DNA mismatch repair genes hMSH2, hMLH1, and hPMS2.

Hereditary nonpolyposis colorectal cancer is a cancer susceptibility syndrome that has been found to be caused by mutations in any of several genes involved in DNA mismatch repair, including hMSH2, hMLH1, or hPMS2. Recent reports have suggested that hMSH2 and hMLH1 have a role in the regulation of the cell cycle. To determine if these genes are cell cycle regulated, we examined their mRNA and protein levels throughout the cell cycle in IMR-90 normal human lung fibroblasts. We demonstrate that the levels of hMSH2 mRNA and protein do not change appreciably throughout the cell cycle. Although hMLH1 mRNA levels remained constant, there was a modest (approximately 50%) increase in its protein levels during late G1 and S phase. The levels of hPMS2 mRNA fluctuated (decreasing 50% in G1 and increasing 50% in S phase), whereas hPMS2 protein levels increased 50% in late G1 and S phase. Our data indicate that, at least in normal cells, the machinery responsible for the detection and repair of mismatched DNA bases is present throughout the cell cycle.

Adenosine Triphosphatases↗
PubMed1997

Effect of resection margins on dermatofibrosarcoma protuberans of the head and neck.

OBJECTIVE: To determine clinical and surgical factors that affect the recurrence of dermatofibrosarcoma protuberans of the head and neck. DESIGN: Retrospective case series of 32 patients who were seen between 1960 and 1995 with a diagnosis of dermatofibrosarcoma protuberans of the head and neck. Data extracted from patients records included sex, age at diagnosis, tumor site, presence or absence of tumor-free margins, initial and salvage treatment, time to recurrence, and status after last treatment. SETTING: Academic tertiary care referral center. INTERVENTION: Surgical excision and radiation therapy. RESULTS: Univariate Kaplan-Meier analysis for recurrence showed the difference in survival to be statistically significant (P < .05) between patients who had wide (> or = 2 cm) surgical margins vs those who had close (< 2 cm) margins. Univariate Kaplan-Meier analysis for recurrence with or without radiation as the grouping variable showed the difference to be statistically significant (P < .01). Similar analyses with sex, age, tumor site, and size of tumor as the grouping variables were not statistically significant. Multivariate Cox regression analysis was used with sex, age, and close or wide margins as variables. Close margins (< 2 cm) had a statistically significant positive correlation with recurrence (P < .05), while sex and age were not associated with recurrence. CONCLUSION: Surgical margins of at least 2 cm should be used in all cases of dermatofibrosarcoma protuberans of the head and neck to prevent recurrence.

Adolescent↗
PubMed1997

Laryngeal chondrosarcomas: the Mayo Clinic experience.

BACKGROUND: Laryngeal chondrosarcomas occur infrequently. Their management is often guided by inferences made from the management of sarcomas arising from more commonly afflicted organs. METHOD: A retrospective analysis of patients with laryngeal chondrosarcomas treated at the Mayo Clinic between 1959 and 1992 was performed to assess prognostic factors and outcomes after various treatments. RESULTS: A total of 20 patients received treatment during this time period. All chondrosarcomas were low grade; 19 involved the cricoid cartilage and one arose in the supraglottic larynx. Initial treatment consisted of local excision (often subtotal removal) alone in 12 patients (60%), hemilaryngectomy in 2 (10%), near total laryngectomy in 2 (10%), and total laryngectomy in 4 (20%). Six patients (30%) had local recurrence: five initially had local excision and one had hemilaryngectomy. All local recurrences or tumor progression developed >3 years after initial treatment. Salvage surgery was performed in five of the six patients who had local recurrence, and the other patient was observed. Of the five patients who had salvage surgery, three required another resection because of a second recurrence. CONCLUSIONS: These results suggest that initial conservative subtotal laryngectomy should be explored further because this treatment may provide long-term voice preservation in most patients, and patients who experience a recurrence after local excision often have been given several years of voice preservation.

Aged↗
PubMed1997

Damage-sensing mechanisms in human cells after ionizing radiation.

Human cells have evolved several mechanisms for responding to damage created by ionizing radiation. Some of these responses involve the activation or suppression of the transcriptional machinery. Other responses involve the downregulation of enzymes, such as topoisomerase I, which appear to be necessary for DNA repair or apoptosis. Over the past five years, many studies have established links between DNA damage, activation of transcription factors that are coupled to DNA repair mechanisms, increased gene transcription and altered cell cycle regulation to allow for repair or cell death via apoptosis or necrosis. Together these factors determine whether a cell will survive with or without carcinogenic consequences. The immediate responses of human cells to ionizing radiation, in terms of sensing and responding to damage, are therefore, critical determinants of cell survival and carcinogenesis.

Animals↗
PubMed1997

Spindle cell carcinoma of the larynx: review of 26 cases including DNA content and immunohistochemistry.

Spindle cell carcinoma (SpCC) is uncommon, with a predilection for the upper aerodigestive tract. Its histogenesis has not been resolved, although most authors support the sarcomatoid carcinoma concept. Ploidy analysis and proliferation indices have not been reported for laryngeal SpCCs. The authors examined the pathological and clinical features of 26 patients (25 men, 1 woman; mean age, 64 years) with laryngeal SpCC treated at the Mayo Clinic from 1960 to 1990. Twenty-three tumors were examined with digital image analysis for DNA content of the spindle cell population (13 tumors had a sufficient squamous component to be analyzed separately). The glottis was involved most frequently (19 patients); 21 tumors were grossly polypoid. Twenty-three tumors were biphasic, and three were monophasic. Overall, 17 tumors (65%) showed keratin positivity in the spindle cell component. Polyclonal antikeratin (15 positive cases), 34betaE12 (15 positive), and AE1/AE3 (12 positive) were the most sensitive markers. Spindle cells were diploid in 5 tumors (22%) and nondiploid in 18 (78%); conventional squamous cell carcinoma was diploid in 4 cases and nondiploid in 9. DNA ploidy results were concordant between the two populations in 11 of 13 tumors (85%). Mean percent MIB-1 staining was 31% in the sarcomatoid component and 45% in the squamous component. In our primary treatment group of 22 patients (median follow-up, 6.4 years), 4 (18%) had local recurrence, 3 (14%) had distant metastasis, and 4 (18%) died of disease. Presence of a nondiploid spindle cell population in 78% of cases of laryngeal SpCC is interpreted as evidence of a neoplastic rather than reactive process. Keratin positivity in nearly two thirds of tumors supports the theory of epithelial origin of these tumors (sarcomatoid carcinoma).

Adult↗
PubMed1997

Spindle cell carcinoma of the larynx and hypopharynx.

We reviewed the clinical records of 34 patients with laryngeal (25) and hypopharyngeal (9) spindle cell carcinomas who were treated at our institution between 1960 and 1990. All the spindle cell carcinomas were studied using paraffin section immunostains, and we performed ploidy analysis of the sarcomatoid component in 31 patients. Of the 31 patients who underwent their initial treatment at our institution, 25 were men and 6 were women (median age at presentation, 64.6 years). A T1 glottic tumor, usually seen as an exophytic firm mass, was the most common type of tumor observed (16 cases). The spindle cells were nondiploid in 86% of the carcinomas, with positive keratin immunostains in 74%. The median follow-up time was 3.7 years. Recurrence of the tumor after partial or total laryngectomy or pharyngectomy occurred in 10 patients. Eight patients died of their disease. The Kaplan-Meier estimate of surviving at least 3 years after initial treatment was 56.8%. Keratin positivity adversely affected the overall survival rate (p < 0.02). The survival rate of patients with hypopharyngeal tumors was worse than that of patients with laryngeal lesions (p < 0.001). The presence of keratin positivity and nondiploid DNA content in the spindle cell population supports the neoplastic epithelial origin of these tumors (sarcomatoid carcinoma). The overall tumor behavior and surgical therapy appeared to be comparable with those of squamous cell carcinomas at a similar stage.

Adult↗
PubMed1997

Immortalized cell lines from embryonic avian and murine otocysts: tools for molecular studies of the developing inner ear.

Recently, our studies have focused on genes expressed at the earliest stages of inner ear development. Our aim is to identify and characterize genes that are involved in determining the axes of the semicircular canals, in otic crest delamination and in early innervation of the inner ear. Many elegant studies of auditory development have been done in animal models. However, the need for large amounts of well-characterized embryonic material for molecular studies makes the development of otocyst cell lines with different genetic repertoires attractive. We have therefore derived immortalized otocyst cells from two of the most widely used animal models of ear development: avians and mice. Avian cell isolates were produced from quail otocysts (embryonic stage 19) that were transformed with temperature-sensitive variants of the Rous sarcoma virus (RSV). Among the individual transformed cells are those that produce neuron-like derivatives in response to treatment with 10(-9) M retinoic acid. Mammalian cell isolates were derived from otocysts, of 9 day (post coitus) embryos of the H2kbtsA58 transgenic mouse (Immortomouse), which carries a temperature-sensitive variant of the Simian Virus 40 Tumor antigen. The vast majority of cells of the Immortomouse are capable of being immortalized at 33 degrees C, the permissive temperature for transgene expression, in the presence of gamma-interferon. Several putative clones et these cells differentiated into neuron-like cells after temperature shift and withdrawal of gamma-interferon; another isolate of cells assumed a neuron-like morphology on exposure to brain-derived neurotrophic factor even at the permissive temperature. We describe also a cell isolate that expresses the Pax-2 protein product and two putative cell lines that express the protein product of the chicken equivalent of the Drosophila segmentation gene engrailed. These genes and their protein products are expressed in specific subpopulation of otocyst cells at early stages. Both mouse and quail immortalized cell lines will be used to study inner ear development at the molecular level.

Animals↗
PubMed1997

HIV/AIDS risk in heterosexual college students. A review of a decade of literature.

Empirical studies dealing with the psychosocial correlates of HIV risk among heterosexual college students are reviewed, including findings related to such theoretical variables as HIV/AIDS-related knowledge, personal and partner's attitudes toward condom use, perceived susceptibility, communication with sex partners, and sexual self-efficacy. Although college students are highly knowledgeable about basic HIV/AIDS facts, they retain some misperceptions about disease transmission. They hold neutral-to-negative hedonistic and practical attitudes about using condoms: those who have engaged in risky behavior accurately perceive their greater susceptibility to infection and experience anxiety regarding transmission of HIV infection. Heterosexual college students communicate infrequently with their partners about safer sex, but they often agree to a partner's suggestion that they use condoms. Higher levels of sexual self-efficacy among college students have been associated with a lower risk for HIV transmission. Limitations and clinical implications of the findings and recommendations for future interventions are discussed.

Condoms↗