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J E Cutler

Publications and source records attributed to J E Cutler.

At least 55 records · Page 3Linked to original sources

A cell surface/plasma membrane antigen of Candida albicans.

Antibody from BALB/cByJ mice immunized against a membranous fraction of Candida albicans agglutinated whole cells as well as the membranous fraction. Hybridoma techniques were used to isolate an IgM monoclonal antibody (mAb) designated 10G which agglutinated whole cells and reacted with the subcellular fraction. Yeast cells of 15 additional C. albicans strains and isolates of C. stellatoidea, C. tropicalis, C. intermedia and C. lusitaniae were also agglutinated by mAb 10G. The antigen was not detected on other fungi, including Candida krusei, C. utilis, Cryptococcus neoformans, Cr. albidus, Torulopsis glabrata, Rhodotorula spp. and Saccharomyces cerevisiae. To determine the cellular location of the epitope to which mAb 10G is specific, freeze-substitution was compared with traditional chemical fixation methods in preparation of samples for immunocolloidal gold electron microscopy (IEM). With both fixation procedures, the antigen recognized by mAb 10G was found randomly and densely concentrated on the plasma membrane on exponential-phase yeast-form cells and had a patchy distribution on the cell wall surface. Association of the antigen with the plasma membrane was confirmed by IEM of isolated membranes. On developing hyphal cells, antigen appeared first on the plasma membrane and later on the cell wall surface. Treatment of yeast cells with beta-mercaptoethanol and Zymolyase before fixation removed the antigen from the surface but left the cytoplasmic antigen undisturbed. Treatment of yeast cells or solubilized antigen with heat or proteolytic enzyme (trypsin, Pronase B, proteinase K) did not remove or destroy the antigen, suggesting a non-protein nature of the epitope.

Agglutination↗

Differential adherence of hydrophobic and hydrophilic Candida albicans yeast cells to mouse tissues.

Using an ex vivo binding assay, we previously demonstrated that yeast cells grown at 37 degrees C display binding specificity in mouse spleen, lymph node, and kidney tissues. In spleen and lymph node tissues, binding was predominantly in regions rich in macrophages. Here, we tested the possibility that hydrophobic and hydrophilic cells bind differentially to host tissues. Hydrophobic and hydrophilic yeast cells of four Candida albicans strains were incubated for 15 min at 4 degrees C with cryostat sections of organs that had been rapidly frozen after removal from BALB/cByJ mice. Unattached cells were removed by washing, and the sections were examined. Hydrophobic cells bound diffusely and abundantly to all tissues, while hydrophilic cell attachment was restricted to specific sites. For example, hydrophobic cells bound to the white and red pulp and the marginal zones in spleens, whereas hydrophilic cells attached primarily to the marginal zones. Hydrophobic yeast cells attached throughout lymph node tissue including paracortical areas, but hydrophilic cell attachment occurred primarily at the subcapsular and trabecular sinuses, EDTA inhibited the adherence of hydrophilic cells but not hydrophobic cells to mouse tissues. Hydrophobic C. albicans strains displaying similar levels of hydrophobicity differed quantitatively in their levels of attachment to kidney and spleen tissues, confirming our earlier observation that surface hydrophobicity is not the sole determinant in adherence to host cells. Other studies have shown that hydrophobic and hydrophilic cells display different virulence characteristics related to their surface properties and that hydrophobic cells are more virulent than hydrophilic cells. Taken together, the present results suggest that the enhanced virulence of hydrophobic cells over hydrophilic cells may be due, in part, to the potential of hydrophobic cells to bind throughout various organs following clearance from the bloodstream.

Animals↗

Evidence for expression of the C3d receptor of Candida albicans in vitro and in vivo obtained by immunofluorescence and immunoelectron microscopy.

The complement conversion product C3d binds to a receptor on the cell surface of Candida albicans. While the function of this receptor is still uncertain, we investigated whether it is expressed during a murine infection. Rabbit antiserum raised against purified receptor was used in conjunction with immunofluorescence microscopy and immunocolloidal gold electron microscopy to examine kidney tissue and peritoneal lavages from infected mice for receptor expression by C. albicans in vivo. Specificity of the antiserum was indicated by reactivity with purified receptor (55 to 60 kDa) and with a protein of similar molecular mass from whole hyphal extracts in Western blots (immunoblots). In vitro analysis by immunofluorescence microscopy showed that the antiserum reacted with both yeast and pseudohyphal forms of the organism, but reactivity was strongest with pseudohyphae. Immunocolloidal gold electron microscopy of fungal cells from peritoneal lavages revealed intense staining of mother cells of germinative forms, germ tubes, and pseudohyphae. Staining of the mother cells was heaviest at the innermost layers of the cell wall but only scant on the cell surface. In contrast, staining was observed throughout the cell walls of germ tubes and pseudohyphae. In kidney, expression of the C3d receptor was found primarily on the cell walls of hyphae and pseudohyphae, although some staining was observed in the cytoplasm. These data support that the C3d receptor of C. albicans is expressed in vivo.

Animals↗

Caffeine and ventricular arrhythmias. An electrophysiological approach.

Little information is known regarding caffeine's effect on the substrate supporting sustained ventricular arrhythmias. This prospective study evaluated the effect of coffee (275 mg of caffeine) on this substrate with programmed ventricular stimulation in 22 patients with a history of symptomatic nonsustained ventricular tachycardia, ventricular tachycardia, or ventricular fibrillation. Patients underwent electrophysiological testing before and 1 hour after coffee ingestion. Mean (+/- SEM) plasma caffeine level achieved after coffee consumption was 6.2 +/- 0.5 mg/L. Mean plasma catecholamine and potassium values were not altered significantly 1 hour following caffeine ingestion. The number of extrastimuli required to induce an arrhythmia was unchanged in 10 patients (46%), increased in six (27%), and decreased in six (27%). Rhythm severity was unchanged in 17 patients (77%), more severe in two (9%), and less severe in three (14%). In those patients with clinical ventricular arrhythmias, caffeine did not significantly alter inducibility or severity of arrhythmias, suggesting little effect on the substrate supporting ventricular arrhythmias.

Adult↗

Analysis of programmed stimulation methods in the evaluation of ventricular arrhythmias in patients 20 years old and younger.

The purpose of this study was to systematically evaluate programmed ventricular stimulation in patients less than 21 years of age undergoing electrophysiologic testing. A standardized protocol was applied in 55 consecutive patients (mean age 14 years) with the following clinical presentations: sustained ventricular tachycardia (VT) (n = 17); ventricular fibrillation (VF) (n = 7); syncope with heart disease (n = 10); nonsustained VT (n = 6); and syncope with an ostensibly normal heart (n = 15). The stimulation protocol consisted of 1 and 2 ventricular extrastimuli during sinus rhythm, followed by 1 to 4 (S2, S3, S4, S5) extrastimuli during pacing at 2 ventricular sites. Of the 17 patients with sustained VT, 12 had induction of the arrhythmia (sensitivity = 71%). Overall, 18 of 55 patients had inducible sustained VT, with this response significantly enhanced by use of S4 or S5 protocols (p = 0.02). Although no syncope patients with an ostensibly normal heart had inducible sustained VT, 7 had polymorphic nonsustained VT in response to ventricular stimulation. The mean number of extra-stimuli preceding the induction of nonsustained or sustained VT or VF did not differ. The induction of VF in 5 cases during this study was preceded in each case by extrastimuli intervals less than or equal to 190 ms. Thus, data indicate that aggressive stimulation protocols appear to be required for induction of sustained VT in most young patients, nonsustained polymorphic VT as a response to aggressive programmed stimulation is of uncertain significance, and that coupling intervals less than or equal to 190 ms may correlate with the induction of VF.

Adolescent↗

Day-to-day reproducibility of antiarrhythmic drug trials using programmed extrastimulus techniques for ventricular tachyarrhythmias associated with coronary artery disease.

Forty-nine patients with coronary artery disease and documented clinical sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) were studied twice in the drug-free state and twice during treatment with an identical antiarrhythmic medication at therapeutic plasma concentrations using an identical programmed electrical stimulation protocol. Tested drugs included procainamide, quinidine, disopyramide and phenytoin. During their 2 paired tests, 11 patients had nearly identical therapeutic plasma concentrations of antiarrhythmic agents (group I) and 38 patients had therapeutic plasma concentrations, but with more variation in drug levels between otherwise identical paired drug tests (group II). Overall, 71% of patients had inducible sustained VT or VF during drug testing. Induced ventricular arrhythmias were not reproducible in 45% of group I patients, despite restudy at nearly identical therapeutic plasma concentrations of an identical antiarrhythmic agent. Induced arrhythmias were also not reproducible in 16% of group II patients. This variability could not be attributed to the electrophysiologic characteristics of the patients studied. Drug trials directed by programmed stimulation should be cautiously interpreted because time-associated changes can mimic a change attributed to a beneficial or deleterious drug effect.

Anti-Arrhythmia Agents↗

Comparison of ventricular arrhythmia induction with use of an indwelling electrode catheter and a newly inserted catheter.

Two methods of serial electrophysiologic testing are in widespread use. Most commonly, the electrode catheter is removed after each study and a new catheter reinserted through the femoral vein for every subsequent test. An alternative method employs an electrode catheter that remains in place during several days of serial testing. Little is known about differences between these two methods with respect to the likelihood of induction of arrhythmia or the frequency of complications. To determine whether inducibility of sustained arrhythmia is altered or if the frequency of complications is unacceptably high with use of an indwelling catheter, a prospective randomized study was conducted in 78 patients. Each patient underwent baseline testing, several days of electropharmacologic testing with an indwelling catheter, a 24 h drug elimination period and placement of a new electrode catheter. Ventricular stimulation studies were then performed in each patient with both the indwelling and new electrode catheters. No differences were found between the indwelling and new catheter tests with respect to induction of arrhythmia, number of extrastimuli required to induce arrhythmia, rate of arrhythmia or requirement for cardioversion. Ventricular pacing thresholds were higher and effective refractory periods were slightly longer when measured with the indwelling catheter. Complications related to the 156 catheter insertions included two that may have been related to the indwelling catheter (one episode of staphylococcal sepsis and one presumed pulmonary embolism) and four that were related to invasive procedures (pneumothorax in all). There were no long-term adverse sequelae of these complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

Cryoablation of medically refractory nodoventricular tachycardia.

Paroxysmal wide QRS tachycardia, based on a nodoventricular accessory connection, is an uncommon arrhythmia. In this report, the endocardial and epicardial mapping and cryoablation of a nodoventricular fiber, documented to participate in medically refractory tachycardia in an 11-year-old boy, are described. Epicardial cryothermia, applied at the earliest site of right ventricular activation, resulted in the abrupt termination of tachycardia. Endocardial cryothermia was subsequently applied in the perinodal region, the presumed site of origin of the nodoventricular fiber. No tachyarrhythmias were inducible postoperatively, and no antiarrhythmic treatment has been required during 18 months of follow-up. Based on precise anatomic localization of the nodoventricular connection, a definitive cure of associated tachyarrhythmias may be possible utilizing cryothermia, without the requirement for extensive intraoperative dissection.

Bundle of His↗

Caveats in the investigation of form-specific molecules of Candida albicans.

Numerous reports purporting the existence of form-specific antigens of Candida albicans have been published, but it is generally unclear whether antigenic variability is an acceptable alternative interpretation. In this study, we used indirect immunofluorescence and immunogold electron microscopy to determine the distribution and form specificities of two antigens during yeast and hyphal growth in several defined and complex media. The results confirmed that antigen expression varies with length of incubation, nutrition, and serotype and indicate that the form specificities of antigens may be misinterpreted when conclusions are based exclusively on indirect immunofluorescence and extraction procedures. We therefore suggest that investigations be designed to include serotype A and B isolates grown in both complex and chemically defined media and that agglutination, immunofluorescence, or enzyme-linked immunosorbent assays on whole cells or cell extracts be used as presumptive tests. Confirmation of form-specific antigens should be done by appropriate immunoelectron microscopic evaluation.

Antigens, Fungal↗

Characteristics of Candida albicans adherence to mouse tissues.

An ex vivo binding assay originally described for determining lymphocyte homing receptors was adapted for studying Candida albicans-host cell interactions in unfixed tissue sections. BALB/cByJ mice were sacrificed, and various organs were removed, rapidly frozen on dry ice, and sectioned. C. albicans yeast cells were suspended to 1.5 x 10(8) cells per ml in Dulbecco modified Eagle medium supplemented with 5% newborn calf serum, and 100 microliters of the suspension was added to tissue sections for 15 min with rotation at 4 degrees C or at 22 to 24 degrees C. The sections were then fixed in glutaraldehyde, washed, and examined. Stationary-phase yeast cells adhered better than log-phase cells, and adherence characteristics were similar at 4 degrees C and 22 to 24 degrees C. Yeast cells from nine strains of C. albicans showed similar tissue specificity. Adherence to lymph node tissue was confined to subcapsular spaces and trabecular sinuses. In the spleen, yeast cells bound to the marginal zones. In both tissues, an association of yeast cells with tissue macrophages was suggested by results with macrophage-specific monoclonal antibodies and fluorescent or immunoperoxidase staining techniques. C. albicans adhered to convoluted tubules, glomeruli, and the tunica media of arterioles in the kidney. During experimentally induced fungemia in mice, C. albicans yeast cells associated with the same tissue sites as in the ex vivo assay, except that binding to renal arterioles was not seen in the in vivo test. A strain of Saccharomyces cerevisiae showed some adherence patterns in common with C. albicans, which indicates that tissue adherence is not sufficient for virulence. Mechanisms of attachment were not determined, but strains of C. albicans varied quantitatively in their ability to attach, and binding was inhibited by chelators of divalent cations.

Adhesiveness↗

Assessment and follow-up of pediatric survivors of sudden cardiac death.

In the young patient resuscitated from sudden cardiac arrest, the risks of recurrence are uncertain and so are the criteria defining therapeutic efficacy for the presumed cause of the initial event. In this study, we analyzed the outcome of 15 consecutive young patients, who were resuscitated from pulseless ventricular tachycardia or ventricular fibrillation and who were evaluated by comprehensive hemodynamic and electrophysiological testing. Patients were 11.2 +/- 2.7 (mean +/- SD) years old at the time of their event, and each was known to have some form of heart disease before sudden cardiac arrest. Ventricular tachycardia or fibrillation was inducible by programmed electrical stimulation in eight patients. Accessory atrioventricular connections, with antegrade effective refractory periods less than 220 msec, were identified in three patients. Sustained atrial flutter was the only arrhythmia inducible in two patients, and no arrhythmias were inducible in two other patients. Surgical or electrophysiological-guided medical therapy resulted in noninducibility of the ventricular arrhythmias in six patients. Surgical division of the accessory atrioventricular connections was performed in three patients, and arrhythmias were not inducible after operation. The four patients with atrial flutter or without defined arrhythmia were treated with an empiric therapy. During 37 +/- 14 months of follow-up, the nine patients with documented noninducibility of a defined cause of sudden cardiac arrest were free of recurrent events. In contrast, during 18 +/- 10 months of follow-up, two of the six patients with empiric therapy or persistent inducibility of ventricular tachycardia died suddenly, and three others had recurrence of ventricular tachycardia or fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Misdiagnosing ventricular tachycardia in patients with underlying conduction disease and similar sinus and tachycardia morphologies.

Six patients presented with wide-complex tachycardias with QRS morphologies similar to those seen on their electrocardiograms that showed normal sinus rhythms. During normal sinus rhythm, each patient had an underlying intraventricular conduction abnormality or bundle branch block. Despite the similarity of the QRS complexes to those seen during sinus rhythm, the tachycardias subsequently proved to be ventricular in origin in each patient. It is important not to misdiagnose these disorders as supraventricular tachycardia as an erroneous diagnosis may result in inappropriate management.

Aged↗

Oral Candida albicans isolates from nonhospitalized normal carriers, immunocompetent hospitalized patients, and immunocompromised patients with or without acquired immunodeficiency syndrome.

A total of 128 human oral isolates of Candida albicans were collected from asymptomatic healthy carriers (64 isolates); asymptomatic, nonimmunosuppressed, hospitalized patients (25 isolates); immunosuppressed transplant patients (19 isolates); and human immunodeficiency virus-infected patients with symptoms of acquired immunodeficiency syndrome and oral candidiasis (20 isolates). Isolates were serotyped as A or B and tested for reactivity with an agglutinating immunoglobulin M monoclonal antibody (H9). Immunocompetent individuals colonized by oral C. albicans were almost equally likely to carry serotype A as serotype B cells, while immunocompromised individuals were at least twice as likely to be infected by serotype B than serotype A strains. The reactivity of isolates with H9 antibody followed a similar but more distinctive pattern. Approximately half of the strains from immunocompetent individuals reacted strongly with H9, and the remainder reacted weakly. However, up to 75% of the isolates from immunocompromised patients reacted weakly with H9, while the remainder reacted strongly. A correlation between H9 reactivity and the serotypes of these isolates existed (P = 0.16). The correlation between H9 reactivity and immune status was even stronger (P = 0.025). The monoclonal antibody activities described above were determined by agglutination tests during defined phases of C. albicans growth. Expression of antigen at various times during growth of several isolates was confirmed at the cellular level by analysis using fluorescence-activated cell sorting. Despite the correlation between serotype A and H9 reactivity, H9 antigen was not identical to the serotype A antigen because four serotype A strains reacted only weakly with H9 antibody, and one strain reacted strongly with H9 but was serotype B. These data indicate that oral strains of C. albicans from immunocompetent individuals differ as a group from C. albicans isolated from those who are immunosuppressed.

Acquired Immunodeficiency Syndrome↗

Long-segment coronary ulcerations in survivors of sudden cardiac death.

Angiographically irregular coronary stenoses usually represent plaque rupture with or without superimposed thrombi. Long-segment coronary stenoses with diffuse irregularities (type IIB morphology) have been shown to be more prevalent than focal irregular lesions (type IIA morphology) in survivors of cardiac arrest without acute myocardial infarction. To further understand the pathogenetic importance of type IIB morphology, the clinical and angiographic characteristics in 59 such patients were analyzed. Type IIB lesions accounted for 63% of all type II lesions. Type IIB patients were older than type IIA patients (p less than 0.05). There was a tendency for type IIB morphology to be associated with more extensive disease than other types of lesion morphology (p less than 0.10). Type IIB morphology probably reflects more advanced atherosclerosis. Platelet microemboli may precipitate spasm and/or acute ischemic ventricular tachyarrhythmias. It is possible that long-segment coronary ulcerations are associated with a higher risk for local coronary thromboembolism, and hence with sudden death, than focal lesions.

Aged↗

Angiographic coronary morphology in survivors of cardiac arrest.

Autopsy studies in victims of sudden coronary death revealed intramyocardial platelet aggregates with microscopic myonecrosis downstream from ruptured atherosclerotic plaques. Ruptured plaques usually manifest angiographically as irregularly bordered (type II) lesions. To investigate the possible pathogenic role of ruptured plaques in arrhythmic death, we analyzed clinical, angiographic, and electrophysiologic data from 49 survivors of cardiac arrest without acute myocardial infarction. All patients had greater than or equal to 50% stenoses of greater than or equal to one coronary artery; 16 had type II morphology, and 33 did not. Type II morphology was more prevalent in patients without inducible sustained monomorphic ventricular tachycardia (11 of 22 or 50%) than in those with it (five of 27 or 19%), p less than 0.05, and patients without akinetic or dyskinetic segments (eight of 14 or 57%) than in those with them (eight of 34 or 24%), p less than 0.06. Thus type II morphology is more prevalent in patients without a demonstrable anatomic and/or electrophysiologic substrate for reentrant ventricular tachycardia, indirectly implicating ruptured plaques in the pathogenesis of cardiac arrest in this subset of patients.

Aged↗