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Biomedical subjects

J E Lewis

Publications and source records attributed to J E Lewis.

At least 19 recordsLinked to original sources

Using reflexive behaviors of the medicinal leech to study information processing.

The interneuronal network that produces local bending in the leech is distributed, in the sense that most of the interneurons involved are activated in all forms of local bending, even those in which their outputs would produce inappropriate movements. Such networks have been found to control a number of different behaviors in a variety of animals. This article reviews three issues: the physiological and modeling observations that led to the conclusion that local bending in leeches is controlled by a distributed system; what distributed processing means for this and other behaviors; and why the leech interneuronal network may have evolved to be distributed in the first place.

Animals

Biomimetic pulmonary surfactants.

Considerable progress has been made in the development of defined mixtures of proteins or peptides with phospholipids which mimic the activity of natural pulmonary surfactants. Several of these biomimetic surfactants are active in animal models and clinical syndromes of surfactant deficiency. This review summarizes the structure and composition of natural surfactants and the development of defined mixtures of peptides and lipids that may be useful in the treatment of respiratory distress.

Amino Acid Sequence

How big should an integrated health care delivery system be at an academic medical center?

The author defines integrated health care delivery systems and comments that there are few such systems now but many in various stages of development. The size of such a system can be described in terms of the number of patients it serves, including their health status and utilization of care, the geographic configuration of the served area, the number of physicians, and the scope and extent of the facilities network. There are a variety of factors that influence a system's size; the author concentrates on the factors that an academic medical center must consider when formulating system-size goals. He discusses (1) the influence of how the institution structures itself to survive; (2) the effects of technology, innovation, and health care costs on the size and organization of these systems; and (3) the effects of the specific characteristics of the institutions' missions of education, research, and patient care. Real numbers describing integrated systems are presented as they relate to three possible institutional goals: economic viability, academic viability, and academic leadership. The author explains why academic medical centers should not try to be only tertiary or quaternary care providers for other integrated health care delivery systems, but at the same time emphasizes that there is no easy or inexpensive way for centers to develop their own systems. Alternative structures for integrated systems are discussed, such as "disease management systems" being developed by the pharmaceutical industry, an "end-to-end linkage" approach, and various ideas to include "captive markets," such as prisoners, university students, and members of communities for the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Academic Medical Centers

Primary head and neck cancer. Histopathologic predictors of recurrence after neck dissection in patients with lymph node involvement.

OBJECTIVE: Retrospectively analyze several histopathologic variables that may predict neck recurrence after neck dissection. DESIGN: From 1970 through 1980, 284 patients with pathologically confirmed metastatic squamous cell carcinoma underwent neck dissection and received no adjuvant therapy. Kaplan-Meier evaluation estimated a 74% 2-year neck recurrence-free rate. After adjusting for the standard covariates of age, gender, neck stage, and tumor grade, we also controlled for the time-dependent covariates of primary recurrence, occurrence in the side of the neck not operated on, or development of new head and neck primary disease. SETTING: A large referral-based practice. RESULTS: The number of lymph nodes involved, invasion of vascular/lymphatic space, invasion of soft tissue, and desmoplastic lymph node pattern adversely affect neck recurrence. A desmoplastic stromal pattern was associated with almost a sevenfold increased risk of neck recurrence. To our knowledge, this finding has not been reported previously. CONCLUSION: Histopathologic evaluation of metastatically involved cervical nodes can identify patients with head and neck cancer who are at high risk for recurrence.

Adult

TXK, a novel human tyrosine kinase expressed in T cells shares sequence identity with Tec family kinases and maps to 4p12.

A gene for a novel, putative cytoplasmic tyrosine kinase, TXK has been isolated from a human peripheral blood cDNA library. The complete nucleotide sequence of the cDNA indicates that it is related most closely to EMT, a tyrosine kinase of T cells and to the B-cell tyrosine kinase Btk, which is mutated in X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency disease (XID) in mouse. TXK, like BTK, is a member of the Tec sub-family of Src-type (non-receptor) tyrosine kinases. Like similar Tec sub-family members, and unlike the other Src kinases, TXK lacks both the N-terminal myristylation signal and the C-terminal regulatory tyrosine. TXK expression is detected primarily in T cells and some myeloid cell lines but not in a number of other cell types. TXK shares 60% amino acid homology with EMT and 57% with BTK over the SH3, SH2 (Src-homology) and catalytic domains but unlike BTK, EMT and tec, it lacks Gap 1 homology and steroid hormone receptor homology in the N-terminal region. Genomic clones containing TXK have been isolated and hybridize to chromosome position 4p12.

Amino Acid Sequence

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

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

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

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

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

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

A study of metastatic cancer found during inguinal hernia repair.

Among 22,816 inguinal hernia repairs done between 1950 and 1988, 15 patients (0.07%) had metastatic tumors found within their hernias. Inguinal herniation was the initial sign of cancer in six patients. A palpable inguinal mass (53%) and abdominal or groin pain (67%) were the most common presenting sign and symptom, respectively. Primary tumor sites included the gastrointestinal tract (40%), ovary (20%), prostate (13%), mesothelium (13%), and unknown sites (13%). The median patient survival was 20 months and depended on the primary tumor site. Grossly apparent inguinal hernia sac abnormalities should be examined microscopically to avoid missing the diagnosis of metastatic cancer, but routine histologic examination of all hernia sacs is not warranted.

Abdominal Neoplasms

Primary squamous cell carcinoma of the parotid gland.

We reviewed all cases of possible primary squamous cell carcinoma of the parotid gland treated at Mayo Clinic, Rochester, Minn, from 1960 through 1988. Eighteen cases of primary squamous cell carcinoma of the parotid gland were identified. We report the clinical behavior and results of treatment of these rare parotid gland neoplasms. The age at diagnosis ranged from 48 to 86 years; the majority of patients were aged 65 years or older. Half of the patients presented with an asymptomatic parotid gland mass; a painful mass occurred in 33% of patients. Facial paralysis was noted in 17%, and a neck was the presenting symptom in 11% of patients. All patients underwent parotidectomy, and all or part of the facial nerve was sacrificed in 66% of patients. A neck dissection was performed in 12 patients, five of whom had pathologic confirmation of neck metastasis. Adjunctive radiation therapy was performed in 55% of patients. The overall survival at 5 years was 50%. Deep fixation and facial nerve paralysis were associated with a poor prognosis. Most recurrences developed within 1 year of initial treatment. Regional recurrence was always associated with a rapid death. Our data suggest that aggressive treatment and early detection may result in a better prognosis than is commonly associated with these tumors.

Aged

Mixtures of synthetic peptides and dipalmitoylphosphatidylcholine as lung surfactants.

Synthetic peptides that differ in their lipid-peptide interactions were combined with dipalmitoylphosphatidylcholine (DPPC) and tested in an adult rat lavaged lung model in vitro for efficacy as totally synthetic lung surfactants. The putative amphipathic alpha-helical region of the major lung surfactant apoprotein (SP-A81-102), an analogue with increased amphipathic alpha-helical potential ([Lys88,97,Glu99,Trp102]-SP-A81-102]), and the hydrophobic peptide gramicidin D were all ineffective. Three water-soluble lipid-binding peptides that contain amphipathic alpha-helical regions were also tested. Of these, only a 24-residue amphipathic alpha-helical peptide (18As) based on the lipid-binding sequences of the plasma apolipoproteins was effective. Melittin and glucagon were ineffective. Mixtures of 18As and DPPC also restored gas exchange in an in vivo lavaged guinea pig lung model to 90-95% of its prelavage value and maintained it for at least 3 h. Mixtures of DPPC and 18As are also surface active (gamma min less than 4 mN/m in the pulsating bubble). These data demonstrate the efficacy of a combination of a single lipid and a small, water-soluble, nonhemolytic, synthetic peptide containing an amphipathic alpha-helical structure and a sequence unrelated to any of the reported lung surfactant apoprotein sequences.

1,2-Dipalmitoylphosphatidylcholine

Laryngeal amyloidosis: a clinicopathologic and immunohistochemical review.

The clinical nature of laryngeal amyloidosis has not been well established, and the natural history of the disease remains a controversial matter. To address these issues, we reviewed the clinicopathologic and immunohistochemical features of 22 cases (11 men and 11 women; mean age, 56 years) of laryngeal amyloidosis. Hoarseness was the most common symptom, and the most frequent site affected was the false vocal cords. Six patients had concomitant tracheal amyloidosis. Paraffin blocks were available for immunostaining in 20 cases. Nineteen cases were positive for amyloid P component. lambda-Light chains were detected in 12 cases and kappa-light chains in 5; three cases did not show definite light-chain staining. Ten patients underwent repeated operations for persistent or recurrent respiratory tract disease. One patient died of progressive tracheobronchial amyloidosis, but systemic amyloidosis did not develop in any of the patients. Laryngeal amyloidosis is a form of localized amyloidosis characterized by monoclonal light-chain deposition. Recurrent respiratory tract disease is not uncommon, but the usual clinical course is relatively benign.

Adult