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Biomedical subjects

J E Lewis

Publications and source records attributed to J E Lewis.

At least 73 records · Page 4Linked to original sources
PubMed1994

Cadherin function is required for human keratinocytes to assemble desmosomes and stratify in response to calcium.

Elevation of the calcium concentration in keratinocyte culture induces the rapid organization of adherens junctions and desmosomes. Formation of these intercellular junctions is accompanied by reorganization of the cytoskeleton and, with a more delayed timecourse, stratification of the culture into a multilayered epithelial cell sheet. Keratinocytes express two cadherins, known as E- and P-cadherin, which are the cell-cell adhesion molecules of the adherens junction. Antibody that blocks E-cadherin function delays the calcium-induced formation of both adherens junctions and desmosomes and leads to an abnormally stratified cultured. In the present study, we show that anti-E-cadherin plus anti-P-cadherin antibodies inhibit the formation of adherens junctions and desmosomes, prevent reorganization of the cytoskeleton, and block stratification. These studies indicate that cadherin function is required for the calcium-induced intercellular junction organization and stratification of human keratinocytes in vitro.

Antibodies, Monoclonal↗
PubMed1994

Tinnitus and suicide.

A retrospective study of tinnitus sufferers who had committed suicide was undertaken. A questionnaire was compiled, and circulated world-wide. Adequate information was obtained on 28 suicides. An association between suicide and left-sided tinnitus reported previously, was not conclusively replicated. In fact, no particular tinnitus parameter, or associated audiological symptom was over-represented in the suicide series. Demographically, tinnitus suicide victims were characterized by being male, elderly, and socially isolated. There was a high prevalence of psychiatric morbidity, in particular depression (70%). A suicide attempt within the year preceding suicide occurred in five individuals.

Adolescent↗
PubMed1994

Lymphoma involving the esophagus.

Fewer than 1% of all lymphomas involve the esophagus; however, lymphoma of the esophagus represents an important cause of dysphagia. This study reviewed all cases of biopsy-proven lymphoma involving the esophagus presenting at our institution between 1945 and 1992. Twenty-seven cases were identified. Three were primary esophageal lymphomas. Eleven percent of the cases presented Hodgkin's disease. Eighty-nine percent were non-Hodgkin's lymphoma. Eighty-nine percent of the patients experienced dysphagia. Eleven lymphomas (41%) were located at the gastroesophageal junction, while the other 17 were in the esophagus proper. Seven of these cases occurred at relapse. Three had mediastinal adenopathy with secondary esophageal involvement. Morbidity included tracheoesophageal fistula in 22%, and surgical repair was performed in half of these cases. Vocal cord paralysis occurred in 22%, with minimal sequelae. Esophageal stricture was present in 30%, usually necessitating dilation. The presentation, diagnosis, and management of this problem are multidisciplinary.

Adult↗
PubMed1994

E-cadherin mediates adherens junction organization through protein kinase C.

Cultured human keratinocytes maintained in 30 microM Ca2+ do not form adherens junctions; however, when the extracellular Ca2+ concentration is raised to 1 mM, adherens junctions form very rapidly. The formation of a junction involves the coordinate organization of intracellular and extracellular components. Cadherins have been shown to mediate this coordinate organization. In this report we show that E-cadherin organizes the various junctional components by signalling through protein kinase C.

Cadherins↗
PubMed1994

Factors affecting survival of patients with tumors of the anterior skull base.

Fifty-four patients with primary neoplasms of the anterior skull base were treated by craniofacial resection with curative intent. The most common tumor was esthesioneuroblastoma (24), followed by squamous cell carcinoma (10). The overall 2-year and 5-year survivals were 75% and 49%, respectively. High-grade tumors, grades 3 and 4, had a poorer prognosis. Tumor size, dural involvement, sphenoid sinus involvement, age, and sex had no significant influence on survival when examined by multivariate survival analysis. Sixteen complications were noted in the postoperative period. Cerebrospinal fluid leakage occurred in 2 patients and loss of frontal bone occurred in 4. There were no operative or perioperative deaths. Craniofacial resection permits surgical resection of the majority of anterior skull base tumors with acceptable morbidity.

Adolescent↗
PubMed1994

Persistent indurated plaques of the face: a variant of Jessner's lymphocytic infiltrate?

Lymphocytic infiltrates of the skin classically include a select number of diagnostic entities such as lupus erythematosus, gyrate erythema, polymorphous light eruption, lymphocytoma cutis, lymphocytic leukemia, and lymphocytic infiltrate of Jessner. We recently observed two patients with chronic inflammatory plaques of the face with histologic features of a lymphocytic infiltrate with unusual clinical features. Persistent indurated plaques of the face may be a manifestation of lymphocytic infiltration of the skin that could represent a variant of Jessner's lymphocytic infiltrate. Cases may be refractory to all forms of treatment other than systemic corticosteroids. Clinicians should be aware of this variant and exclude lupus erythematosus and photodermatitis.

Adult↗
PubMed1993

Esthesioneuroblastoma: the role of adjuvant radiation therapy.

PURPOSE: We describe our experience with adjuvant radiation therapy in patients who underwent operation for esthesioneuroblastoma. METHODS AND MATERIALS: Between January 1951 and December 1990, 49 patients with esthesioneuroblastoma received their initial treatment at the Mayo Clinic. There were 27 male and 22 female patients; their ages ranged from 3 to 79 years (median, 54 years). The tumors were Kadish Stage A in 4 patients, Stage B in 13, Stage C in 29, and modified Kadish Stage D in three (cervical nodal or distant metastasis). The tumors were graded according to Hyams' classification. Treatment included gross total resection alone in 22 patients and gross total resection and postoperative adjuvant radiation therapy in 16. The patients treated with adjuvant radiation had a greater proportion of advanced-stage and high-grade tumors. RESULTS: The 5-year actuarial overall survival, disease-free survival, and local control rates were 69.1% + 7.0%, 54.8% + 7.6%, and 65.3% + 7.4%, respectively. The only significant predictor for overall survival, disease-free survival, and local control was Hyams' grade. Local control was improved in patients who received postoperative adjuvant radiation even though this group of patients had more advanced and higher-grade tumors (5-year rate of local control was 85.9% + 9.3%, compared with 72.7% + 9.5% for those who had operation alone, p = 0.26). CONCLUSION: Adjuvant radiation therapy for esthesioneuroblastoma improves local tumor control, particularly for high-grade and high-stage tumors. We recommend additional treatment with radiation (55.5 Gy) after complete resection of esthesioneuroblastoma.

Adolescent↗
PubMed1993

Amphipathic alpha-helical peptides based on surfactant apoprotein SP-A.

Three peptides based on the putative amphipathic helical region of the major pulmonary surfactant apoprotein (SP-A) were synthesized by solid-phase techniques, mixed with DPPC and tested for efficacy as lung surfactants in an in vitro adult rat lavaged lung model. The peptides correspond to residues 81-102 (SP-A81-102) and 78-101 (SP-A78-101) of the native human sequence and an analog with increased hydrophobicity, Leu84,90SP-A78-101. Neither native sequence was effective in simple mixtures with DPPC. However, substitution of leucine residues for Asp84 and Thr90 of SP-A81-102 yielded a peptide which was active in mixtures with DPPC, restoring quasi-static lung compliance to 90% of the unlavaged value. In the absence of peptide, DPPC had no effect on the P-V curve of the lavaged lung. The activity of the Leu84,90 analog correlated with an increased amphipathic alpha-helical potential and an improvement in several predictive parameters for lipid-binding. The similarities between this active peptide and other active amphipathic alpha-helical peptides lend support to the hypothesis that amphipathic alpha-helical potential and the size of the hydrophobic face are critical for functional synthetic surfactant peptides in simple mixtures with dipalmitoylphosphatidylcholine.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1993

Polymerase chain reaction (PCR) identification of human papillomavirus (HPV) DNA in verrucous carcinoma of the larynx.

The incidence of human papillomavirus (HPV) DNA in archival formalin-fixed, paraffin-embedded tissue sections from verrucous carcinoma of the larynx was determined using polymerase chain reaction (PCR) with consensus primers and by in situ hybridization designed to detect HPV types 6/11, 16/18, 31/33/35. HPV DNA was detected in 17 (85%) of 20 tissue samples by PCR; none of the 20 samples were positive for the seven genotype types tested by in situ hybridization. PCR is a valuable tool to detect HPV and therefore will significantly clarify the importance of HPV in squamous mucosal disorders.

Adult↗
PubMed1993

P- and E-cadherin are in separate complexes in cells expressing both cadherins.

E- and P-cadherin are members of a family of calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, the transmembrane cadherins self-associate, while intracellularly, they interact with the actin-based cytoskeleton. Several intracellular proteins, collectively termed catenins, are tightly associated with E- and P-cadherin. These proteins appear to link the cadherin to the cytoskeleton and have been proposed to be involved in concentrating cadherins at cell-cell adherens junctions. In this paper we report the production of monoclonal antibodies against both alpha- and beta-catenin and use these antibodies to show that in cells simultaneously expressing two different cadherins, E-cadherin and P-cadherin, each cadherin appears to be present in a separate cadherin/catenin complex.

Antibodies, Monoclonal↗
PubMed1993

Congenital duodenal obstruction: a 32-year review.

Although survival in infants with congenital intestinal obstruction has improved, duodenal obstruction continues to present unique challenges. One hundred thirty-eight newborns and infants (aged 0 to 30 days) were treated for congenital duodenal obstruction. Sixty-five were boys and 73 were girls. Sixty-one (45%) were premature. Forty-six had an intrinsic defect (atresia, web, stenosis, or duplication), 64 had an extrinsic defect (annular pancreas or malrotation with congenital bands), while 28 had various combinations of these. Presenting signs included vomiting (90%, bilious in 66%), abdominal distention (25%), dehydration (24%), and weight loss (17%). Although plain film abdominal x-ray was diagnostic in 58%, upper and/or lower gastrointestinal contrast studies were obtained in 71% of infants to confirm diagnosis. Thirty-eight percent of patients had associated anomalies, including Down's syndrome (11%), cardiac defects, other atresia, other trisomy syndrome, imperforate anus, and central nervous system anomalies. Fourteen patients (10%) had 3 or more other anomalies, many of which required additional surgical therapy. The operative repair of the various defects included Ladd's procedure for malrotation (31%), duodenoduodenostomy (14%), duodenojejunostomy (22%), gastrojejunostomy or gastroduodenostomy (4%), excision of the web and duodenoplasty (3%), or combination of the above (22%). Gastrostomy was placed in 61%. One hundred twenty-eight patients survived (93%). The causes of death were combinations of sepsis, pneumonia, brain hemorrhage, short bowel, and cardiac anomaly. Eight of 10 (80%) who died had other serious anomalies. Twenty patients (14%) required reoperation 5 days to 4 years postoperatively for obstructing lesions (5), wound dehiscence (3), anastomotic leak or dysfunction (6), other atresias (2), choledochal cyst (1), pyloric stenosis (1), and gastroesophageal reflux (2).(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenal Obstruction↗
PubMed1993

An amphipathic alpha-helical decapeptide in phosphatidylcholine is an effective synthetic lung surfactant.

An idealized model amphipathic alpha-helical decapeptide was synthesized and tested for efficacy as a totally synthetic lung surfactant in simple mixtures with dipalmitoylphosphatidylcholine (DPPC). Quasi-static lung compliance was restored to 92 +/- 3% of the unlavaged value at a pressure of 5 cm H2O in an in vitro lavaged rat lung model. A sustained improvement in gas exchange was also observed when guinea pigs were treated with the synthetic lung surfactant in an in vivo lavaged lung model. DPPC/peptide mixtures rapidly formed low surface tension films in the pulsating bubble surfactometer consistent with a mechanism in which the lipid and peptide mixture spreads rapidly in the lavaged lung to minimize the surface tension at the air/tissue interface. This decapeptide sequence is active in mixtures with DPPC whether the residues are in the all L or all D conformation. However, a peptide with identical sequence, but with alternating D and L amino acid residues, is relatively inactive. Positive charge interactions are not important since a peptide with formylated lysine residues is active. The activity of these decapeptides, with sequences unrelated to any of those in natural lung surfactants, shows that the classic amphipathic alpha-helical hypothesis may be useful in designing peptides that will be effective synthetic lung surfactants in binary mixtures with DPPC. The data demonstrate that a small water-soluble synthetic peptide containing an amphipathic alpha-helical structure combined solely with the major lipid of natural lung surfactant is effective in restoring lung compliance and gas exchange in surfactant-deficient lungs and may be useful in treatment of the respiratory distress syndromes.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1993

Esthesioneuroblastoma: prognosis and management.

Forty-nine patients with esthesioneuroblastoma were treated at the Mayo Clinic between 1951 and 1990. Their clinical manifestations and treatment results were reviewed to identify possible prognostic factors. The 5-year survival rate for all patients was 69%. Tumor progression occurred in 25 patients (51%; no local control in 6 and local recurrence in 19). Metastasis was found in 15 patients (31%; regional in 10 and distant in 9). Nineteen patients died directly from metastatic or intracranial tumor extension. The pathological grade of the tumor was the most significant prognostic factor identified. The 5-year survival rate was 80% for the low-grade tumors and 40% for the high-grade tumors (P = 0.0001). Surgical treatment alone is effective for low-grade tumors if tumor-free margins can be obtained. Radiation is used for low-grade tumors when margins are close, for residual or recurrent disease, and for all high-grade cancers. The poor prognosis associated with high-grade tumors may also mandate the addition of chemotherapy. Recurrent tumor and regional metastasis should be treated aggressively because this approach has been shown to be worthwhile. A craniofacial resection is now the surgical procedure performed in all cases. Because recurrence can occur after 5 or even 10 years, long-term follow-up is mandatory.

Adolescent↗
PubMed1993

Role of the hydrophobic face of amphipathic alpha-helical peptides in synthetic pulmonary surfactants.

The sequence requirements for the peptide component of a totally synthetic lung surfactant mixture were examined. A series of model amphipathic alpha-helical peptides (MAP) with six to 18 residues were synthesized by solid phase techniques, mixed with dipalmitoylphosphatidylcholine (DPPC) and tested for efficacy in an in vitro adult rat lung model. The most effective peptide in these mixtures contained 10 residues. Peptides containing eight and 14 residues were also highly active when mixed with DPPC in buffer, but a six-residue peptide was inactive. Longer peptides were active only when mixed with DPPC in trifluoroethanol before swelling in buffer; no other lipids were required to elicit high activity. Biologically effective peptides, when combined with DPPC, formed translucent mixtures that were significantly less turbid than ineffective mixtures, dramatically decreased the enthalpy of the main phase transition of DPPC and reduced the gamma min in the pulsating bubble surfactometer. Turbidity and minimal surface tensions were significantly correlated with activity in this series of peptides. These data show that effective synthetic lung surfactants may be prepared with mixtures of DPPC and idealized amphipathic alpha-helical peptides containing as few as eight to 10 residues. They lend further support to the hypothesis that amphipathic alpha-helical peptides with hydrophobic surface areas greater than approximately 6.5 nm2 in simple mixtures with DPPC are biologically active.

Amino Acid Sequence↗
PubMed1992

Phase resetting and fixed-delay stimulation of a simple model of respiratory rhythm generation.

In a previous study (Lewis et al., 1990), the response of the respiratory rhythm to a perturbing stimulus was investigated using two different stimulus protocols: phase resetting and fixed-delay stimulation. The first protocol consists of measuring the effects of perturbing an oscillator at different phases of the cycle on the duration of the perturbed cycle. The resulting phase response curves (PRCs) can be used to characterize the properties of the oscillator (Winfree, 1980). A second protocol, fixed-delay stimulation, involves perturbing an oscillator at a fixed latency from the onset of the cycle, repeated every n-th cycle. If a single stimulus produces an effect that lasts longer than a single cycle, complicated responses can be expected from fixed-delay stimulation (Lewis et al., 1987). A simple three-phase model for respiratory rhythm generation based on a hypothesis by Richter and coworkers (1982, 1983, 1986) was investigated in the context of these experimental studies. Phase resetting and fixed-delay stimulation protocols were simulated in the model. PRCs of the model resemble those obtained experimentally: a phase-dependent prolongation or shortening of the inspiratory phase depending on the stimulus magnitude, and a slight prolongation of the expiratory phase. Stimuli delivered to the model repetitively during successive inspiratory periods at a fixed-delay produced various combinations of shortened and prolonged cycles, similar to those observed in the experiments. However, the marked increases in cycle duration observed in the experiments during, as well as after, stimulation were not evident in the model. These comparisons suggest that (1) PRCs may not be an adequate way to evaluate certain models of rhythmogenesis, and (2) to improve the present simplified formulation of the three-phase model of the respiratory oscillator, time-varying stimulus dependent effects should be incorporated.

Animals↗