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J T Johnson

Publications and source records attributed to J T Johnson.

At least 19 recordsLinked to original sources
PubMed1996

Extracapsular spread in the clinically negative neck (N0): implications and outcome.

Cervical metastasis is the most important prognostic factor in head and neck cancer patients. The prognostic significance of extracapsular spread of tumor in metastatic lymph nodes has also been documented. The presence of extracapsular spread further reduces the survival by 50% in those patients with cervical metastatic disease. Most patients with clinically negative necks (stage N0) have a good prognosis. However, some of these patients will have neck disease and distant metastasis and will eventually die. Because the presence of extracapsular spread is a predictor of poor outcome, we hypothesized that extracapsular spread may be a factor in the subset of patients with clinically negative necks who have poor outcomes. One hundred nine patients with clinically negative necks who had undergone neck dissection were identified. Occult metastasis was observed in 34% of patients. In this group, extracapsular spread was present in 18 (49%) patients. Overall, 103 patients were evaluable, of whom 70 (68%) remain free of disease 2 or more years after treatment. A subgroup of 68 patients had histologically negative nodes, of whom 56 (82%) are free of disease. Of patients with extracapsular spread, only 5 (31%) of 16 are free of disease. This is in contrast to patients with metastasis confined to the lymph node, of whom 9 (47%) of 19 are free of disease. Statistical analysis of these data shows that for this sample size this difference is significant. The addition of radiation therapy did not improve outcome in these patients. Extracapsular spread predicts a worse outcome in patients with subclinical cervical metastasis. Alternative modes of adjuvant therapy are suggested because of the poor results of postoperative radiation therapy in patients with extracapsular spread.

Carcinoma, Squamous Cell↗
PubMed1996

Single screw fixation for acute and acute-on-chronic slipped capital femoral epiphysis.

Charts and radiographs of 78 patients with slipped capital femoral epiphysis were reviewed. During the retrospective study period, 1990 to 1993, 16 patients had acute or acute-on-chronic slips; 21 hips were involved. Nine hips were acute and 12 hips were acute-on-chronic slips. No patient reported endocrinopathy or other systemic illness. All hips were fixed with a single 7-mm cannulated screw. No attempts were made for reduction. The lateral head-shaft angle (preoperative, postoperative, and at followup) was measured as was the position of the screw (postoperative and followup). Physeal closure in 19 hips occurred at a mean of 9.6 months. Two additional patients did not return for followup until 30 and 36 months after surgery. At closure, there was no significant change in head-shaft angle from preoperative position. No cases of avascular necrosis or chondrolysis were seen in this series. Seventeen of the 21 hips had an excellent functional result. Three hips had a good result and 1 had a poor result. There was a tendency for poor pin position and less satisfactory results to be associated. It is concluded that single screw fixation is adequate for treating uncomplicated acute and acute-on-chronic slipped capital femoral epiphyses.

Acute Disease↗
PubMed1995

Microsatellite instability in oral cancer.

Generalized genomic instability, detected as somatic changes in allele sizes at microsatellite loci in tumors compared to peripheral lymphocyte DNA, is a recently recognized mechanism of mutation in cancer. Such instability results from the somatic loss of DNA mismatch repair capability. Germ-line mutations at DNA mismatch repair loci confer susceptibility to colon cancer in hereditary non-polyposis colorectal cancer. Somatic loss of DNA mismatch repair has been reported in a large variety of other tumor types. Our goal was to determine the frequency of microsatellite instability in a large series of oral tumors. Out of 91 tumors analyzed for microsatellite instability, 6 (7%) showed microsatellite instability. Instability was observed at multiple loci with a range of 50-74% of loci affected. Alterations include both increase (74%) and decrease (26%) in allele sizes. The proportion of alleles affected ranged from 30-58% of all alleles. Our data suggest that somatic genomic instability plays a role in the pathogenesis of a small subset of oral tumors.

Adult↗
PubMed1995

Natural killer (NK) cells as effectors of antibody-dependent cytotoxicity with chimeric antibodies reactive with human squamous-cell carcinomas of the head and neck.

In patients with cancer, antibody-dependent cellular cytotoxicity (ADCC) may be used as a laboratory test or for enhancing immunotherapy with murine monoclonal or chimeric mouse/human anti-tumor antibodies (mMAbs or cMAbs, respectively). We have established an ADCC assay with IgG1 cMAb SF-25, using human squamous-cell carcinoma of the head and neck (SCCHN) cell lines as targets. By flow cytometry, all SCCHN cell lines tested expressed the antigen recognized by cMAb SF-25. Trypsinization of the cell monolayers facilitated binding of cMAb SF-25 to the antigen on the cell surface of SCCHN targets. Using the PCI-50 SCCHN cell line as a target coated with this cMAb at the optimal concentration of 1.0 micrograms/ml, normal human peripheral blood mononuclear cells (PBMC, n = 28) were found to mediate ADCC at a mean level of 283 +/- 42 (SEM) lytic units (LU20/10(7) effector cells). Non-adherent monocyte-depleted PBMC and natural killer (NK) cells purified by negative selection mediated significantly higher levels of ADCC than unseparated PBMC against SCCHN targets. NK cells, defined as CD3-CD56+ cells, could be effectively armed by cMAb SF-25, as confirmed by flow cytometry and ADCC assays. IL2-activated armed NK cells mediated higher levels of ADCC than non-armed NK cells. Binding of cMAb SF-25 to NK cells and their ADCC were enhanced by pre-incubation with polyethylene glycol. Arming of NK cells with chimeric antibodies should be considered in developing novel strategies for treatment of human SCCHN, especially in the adjuvant setting.

Antibodies, Monoclonal↗
PubMed1995

Oral pilocarpine for radiation-induced xerostomia: integrated efficacy and safety results from two prospective randomized clinical trials.

PURPOSE: Pilocarpine hydrochloride administered in either a fixed-dose or in a dose-titration protocol three times a day for 12 weeks was evaluated for its ability to relieve symptoms of postradiation xerostomia and to improve saliva production. The studies were randomized, double-blind, placebo-controlled, multicenter clinical trials. A total of 369 patients who had received at least 40 Gy of radiation to the head and neck with clinically significant xerostomia were enrolled in the two studies. In the dose-titration study, 162 patients were enrolled and they received a thrice daily regimen of 2.5 mg tablets for first 4 weeks, 5.0 mg tablets for the second 4 weeks, and 10.0 mg tablets for last 4 weeks of a 12-week study. Patients in the titration study were allowed to down titrate following at least one dose escalation to alleviate bothersome side effects, if any. In the fixed dose study, 207 patients received either placebo, 5.0 mg, or 10.0 mg tablets t.i.d. for 12 weeks. METHODS AND MATERIALS: Patients were evaluated for symptomatic relief by responding to questionnaires using visual analog scales and categorical questions; and, for saliva production by sialometry. Questionnaires measured relief of intraoral dryness, improvement in overall condition (global response), oral discomfort, difficulty in speaking, chewing and swallowing, denture wearing, and usage of artificial saliva. Evaluations were conducted at baseline, and weeks 4, 8, and 12. RESULTS: There were statistically significant improvements in salivary flow in pilocarpine treatment groups vs. placebo. There was a significant improvement in the overall "global" condition of xerostomia associated with the use of pilocarpine in both studies. In the fixed-dose study, there were significant improvements in oral dryness, mouth comfort, ability to speak, and reduction in the use of oral comfort agents. The dose-titration study showed improvements in dryness that approached significance (p = 0.057) and a decreased use of oral comfort agents (p = 0.045). All pilocarpine dosages (2.5, 5.0, and 10.0 mg three times a day) were judged to be safe. Adverse experiences were those expected for a cholinergic agonist, with the most common being mild to moderate sweating. The incidence of these events increased by dose. CONCLUSION: It is concluded that in these studies pilocarpine produced clinically significant benefits with acceptable side effects and risks for the treatment of symptomatic postradiation xerostomia. The incidence of most adverse events increased with dose. Best results may require continuous treatment for more than 8 weeks with doses greater than 2.5 mg three times a day. A 5.0 mg thrice daily regimen produced the best clinical results when both efficacy and side effects were taken into consideration. There may be some patients who would experience some additional benefit by increasing the dose to 10 mg thrice daily.

Administration, Oral↗
PubMed1995

T3 glottic carcinoma revisited. Transglottic vs pure glottic carcinoma.

OBJECTIVE: To compare results of treatment of patients who have T3 transglottic carcinoma with patients who have T3 pure glottic carcinoma. DESIGN: A retrospective cohort study from January 1976 to December 1990 with a minimum 2-year follow-up. SETTING: Eye and Ear Hospital, University of Pittsburgh Medical Center. PATIENTS: The medical records of 161 patients with T3 glottic carcinoma were reviewed. We excluded 17 patients who were unavailable for follow-up or who had died of other causes but were free of glottic carcinoma. Therefore, 144 patients were entered into this study--79 patients with transglottic carcinoma and 65 with pure glottic carcinoma. INTERVENTION: Three treatment groups consisted of the following: 30 patients in whom a full course of radiation therapy failed and who subsequently underwent salvage surgery; 92 patients who underwent surgery only; and 22 patients who underwent surgery and had postoperative radiation therapy. Seventy-five patients had total laryngectomy, and 69 had total laryngectomy with neck dissection. MAIN OUTCOME MEASURES: Cervical metastasis, extracapsular spread, local failure, stomal recurrence, distant metastasis, and 2 years with no evidence of disease. RESULTS: Patients with T3 transglottic carcinoma had a higher incidence of occult cervical metastasis (12% vs 9%), overall cervical metastasis (27% vs 17%), and extracapsular spread (43% vs 27%) than did patients with T3 pure glottic carcinoma. Two years of no disease was similar in these two groups (80% vs 79%). Extracapsular spread had a notable effect on distant metastasis and on 2 years of no disease. CONCLUSION: Patients with T3 transglottic carcinoma had a higher incidence of cervical metastasis and extracapsular spread than patients with T3 pure glottic carcinoma. Every patient with T3 transglottic carcinoma should be treated with total laryngectomy with neck dissection.

Adult↗
PubMed1995

Cost analysis of antibiotic prophylaxis in clean head and neck surgery.

OBJECTIVE: This study was undertaken to assess the excess cost of hospitalization accrued to patients who develop postoperative wound infection following neck dissection in which the wound was not exposed to secretions from the upper aerodigestive tract. DESIGN: A retrospective cohort of patients who underwent "clean" neck dissection from 1976 to 1989 were evaluated. Antibiotic administration (yes or no), post-operative wound infection (yes or no), and duration and cost of hospitalization were assessed. SETTING: All surgeries were performed in a university medical center. PATIENTS: All patients underwent neck dissection in which the procedure was clean, ie, there was no exposure to secretions from the upper aerodigestive tract. MAIN OUTCOME MEASURES: Patients were assessed to determine administration of antibiotics (yes or no), development of postoperative wound infection (yes or no), and duration and cost of hospitalization. RESULTS: Wound infection developed in 10 (10%) of 99 patients who did not receive antibiotics. Of 93 patients who received perioperative antibiotics, three (3.3%) developed wound infection. This difference was not statistically significant. The type II (beta) error was greater than 0.2, suggesting that a significant difference may have been missed (false-negative) as a result of the small number of patients studied. The excess cost accrued to each patient who developed a postoperative wound infection was in excess of $36,000 (1992 dollars). The cost of administration of antibiotic prophylaxis to 100 patients is less than this amount. CONCLUSION: The decision to withhold antibiotic prophylaxis should not be made in an effort to reduce hospital costs.

Adult↗
PubMed1995

Floor of mouth carcinoma. The management of the clinically negative neck.

OBJECTIVES: Examine the management of the clinically negative neck and evaluate the role of elective neck dissection in patients with squamous carcinoma of the floor of the mouth. DESIGN: Retrospective analysis of a cohort of patients with squamous carcinoma of the floor of the mouth and N0 stage disease of the neck who were treated between 1973 and 1992. The mean follow-up was 6 years. PATIENTS: The cohort consisted of 129 patients. Excluded from analysis were patients without evidence of disease but less than 3 years of follow-up and those with uncertain resection margins. INTERVENTION: Resection of the floor of the mouth lesion with or without marginal mandibulectomy. Elective lymphadenectomy was performed in 26 (23%) of the 129 patients. OUTCOME MEASURE: Estimates were obtained of survival according to mode of therapy, classification of treatment modality, determinate cure, locoregional failure, salvage, and occult disease by clinical stage. RESULTS: Occult disease was detected in 23% of the patients who underwent elective neck dissection. Recurrence in the neck occurred in 36% of 103 patients who received follow-up but did not undergo elective neck dissection. The determinate survival at 3 years was 100% for patients with occult disease who underwent elective neck dissection. Overall, 96% of the patients who were treated with elective neck dissection were cured; 85% of the patients who received no initial treatment of the neck were cured; and 59% of the patients with failure in the neck were salvaged. CONCLUSIONS: A more aggressive approach to the neck with N0 disease may be warranted. Selective neck dissection allows early removal of occult metastases with acceptable morbidity. In elective dissection for clinically and histologically negative necks, the high rate of survival may result from the removal of metastatic carcinoma that was missed in the histopathologic sampling process.

Adult↗
PubMed1995

Production by human squamous cell carcinoma of a factor inducing activation and proliferation of immune cells.

OBJECTIVE: To examine supernatants (SNs) of human squamous cell carcinoma of the head and neck cell lines for soluble tumor-derived factors capable of inducing activation and proliferation of human immune cells. DESIGN: The SN of squamous cell carcinoma of the head and neck cell line PCI-50 was cultured in serum-free medium and tested for the ability to induce expression of activation antigens, proliferation, cytotoxicity against tumor cell targets and cytokine production by purified human natural killer (NK) and CD4+ T cells. RESULTS: Supernatant of PCI-50 promoted expression of the following activation markers on NK and T cells: CD25 (interleukin-2R-alpha), HLA-DR (major histocompatibility complex class II), CD54 (ICAM-1), CD71 (transferrin receptor), and CD69 (activation-inducing molecule). In addition, SN induced and significantly sustained (P < .01) proliferation of human unseparated peripheral blood lymphocytes and NK or T cells in culture. Purified human NK or T cells cultured in the presence of the SN and IL-2 (120 IU/mL) had significantly higher antitumor cytotoxicity than that mediated by NK or T cells cultured in AIM-V medium and IL-2. The SN induced cytokine (interferon gamma, tumor necrosis factor alpha, interleukin-6) production in purified NK or T cells. When the SN was fractionated by molecular weight-based filtration into fractions greater and less than 30 kd, the growth- and cytotoxicity-promoting activities were consistently detectable in the greater than 30-kd fraction. CONCLUSIONS: Culture SN of squamous cell carcinoma of the head and neck cell lines contain a soluble factor(s) capable of activating NK and CD4+ T cells and of promoting growth and antitumor cytotoxicity of these lymphocyte subsets in vitro.

Antigens, CD↗
PubMed1995

Visualization of INT2 and HST1 amplification in oral squamous cell carcinomas.

Oral squamous cell carcinoma (OSCC) develops along a multistep genetic pathway including loss of tumor suppressor genes and alteration of oncogenes. We characterized seven OSCC cell lines by classical and molecular cytogenetic analysis and fresh tumor and adjacent oral mucosa corresponding to three of the cell lines by molecular cytogenetics. We observed homogeneously staining regions (hsrs) in four of the seven cell lines, at 11q13 in three and at 11q23 and in an unidentified marker chromosome in the fourth. Amplification of band 11q13 occurs in 30-60% of head and neck squamous cell carcinomas. To determine whether INT2 and HST1, both located in band 11q13, are amplified in the tissues and cell lines and to confirm the chromosomal location(s) of the amplification, we used dual-color fluorescence in situ hybridization (FISH) with DNA probes for these genes and the chromosome 11 centromere. We report chromosomal localization of INT2/HST1 amplification in OSCC. Coamplification of INT2 and HST1 was detected in the hsrs in cultured tumor cells from the four hsr-containing tumors and in directly harvested tumor cells, which were available from only two of these tumors. Amplification was not present in tumors lacking hsrs or adjacent oral mucosa corresponding to any of the seven tumors. The observation of amplification in fresh tumor cells suggests that the amplification was present in the patients, may play a key role in the development and/or progression of OSCC, and is not due to karyotypic evolution in vitro. The absence of amplification in the adjacent mucosa suggests that 11q13 amplification is a relatively late event in OSCC tumorigenesis.

Biopsy↗
PubMed1995

Post-radiation primary intranodal leiomyosarcoma.

An unusual case of post-radiation primary intranodal leiomyosarcoma of the cervical lymph node is presented. The patient was a 32-year-old white man who was treated in 1986 with hemiglossectomy and right neck dissection, followed by radiation therapy, for squamous cell carcinoma of the tongue. Six years later, he presented with an enlarged left cervical lymph node which on biopsy showed a high grade spindle cell malignant neoplasm. Immunohistochemistry and electron microscopic study verified the smooth muscle origin of the tumour. Extensive work-up for a second primary lesion was negative. Primary intranodal leiomyosarcoma is extremely rare. We briefly discuss the histological differential diagnosis of spindle cell lesions of lymph nodes, leiomyosarcoma of the vessel wall and radiation-associated sarcoma.

Adult↗
PubMed1995

Adult respiratory papillomatosis: human papillomavirus type and viral coinfections as predictors of prognosis.

Pathologic material and the records of 29 patients with laryngeal papillomatosis were reviewed. The relationship between the type of human papillomavirus (HPV) and the presence of viral coinfections was correlated with clinical outcome. Using polymerase chain reaction, paraffin-embedded specimens were analyzed for the presence of HPV, Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV). The HPV type could be identified in 24 patients' specimens. Twenty-one patients were infected with HPV type 6. The other 3 were infected with HPV type 11 or 16. Three patients developed squamous cell carcinoma, of whom 2 had HPV type 11 or 16. We found HSV, EBV, and CMV in 50%, 12.5%, and 0% of specimens, respectively. An aggressive clinical course was observed in 17 patients. Evidence of coinfection with other viruses was identified in 11 (65%) of these patients. In contrast, a benign clinical course was observed in 7 patients, of whom 2 (29%) had viral coinfections. We conclude that the HPV type and the presence of viral coinfections may be predictive of an aggressive clinical course.

Adult↗
PubMed1995

Prognostic significance of prostaglandin E2 production by mononuclear cells and tumor cells in squamous cell carcinomas of the head and neck.

Prostaglandin E2 (PGE2) has been implicated as a cause of immunosuppression in patients with head and neck cancer. To determine the relative contribution of tumor cells and mononuclear cells to PGE2 levels in vivo, tumor cells and tumor-infiltrating mononuclear cells (TIMC) were isolated from fresh tumor biopsy specimens of 23 patients with squamous cell carcinoma of the head and neck (SCCHN) by using enzymatic digestion and differential gradient centrifugation. Peripheral blood mononuclear cells (PBMC) and lymph node mononuclear cells (LNMC) from metastatic and nonmetastatic lymph nodes were also isolated. Cell fractions were cultured for 24 hours, and PGE2 levels of supernatant were determined by radioimmunoassay. PGE2 production by LNMC was significantly decreased compared to tumor cells, TIMC, and PBMC (P = .0002). LNMC from metastatic lymph nodes produced significantly higher levels of PGE2 (P = .02) compared to nonmetastatic lymph nodes. Although T stage was not correlated with PGE2 production by TIMC or tumor cells, advanced N stage (N1-3) was associated with decreased PGE2 production by TIMC (P = .006). These results suggest that both tumor cells and TIMC are sources of PGE2 in tumor tissues of patients with SCCHN and that decreased PGE2 production by host inflammatory cells may have clinical significance in the development of cervical metastases.

Adult↗
PubMed1995

Flow cytometric analysis of primary and metastatic squamous cell carcinoma of the oral cavity and oropharynx.

A retrospective analysis of formalin-fixed, paraffin-embedded tissue from patients with histologically confirmed metastatic squamous cell carcinoma was performed using flow cytometry. Ninety-eight sets of specimens from previously untreated patients with an oral cavity or oropharyngeal tumor and a simultaneous cervical metastatic deposit were analyzed. Normal mucosa and cervical lymph nodes were processed identically and run as controls. All patients underwent surgical resection at Wilford Hall USAF Medical Center or The Eye and Ear Hospital of Pittsburgh between 1980 and 1986. The specimens from 94 patients were technically adequate for interpretation. Diploid histograms in both the primary and metastatic tumors were present in 49 (52%) of 94 patients. Aneuploid histograms in either the primary and metastatic tumors were noted in 45 (47%) of 94 patients. In this group of 45 patients, the primary tumor and cervical metastasis were both aneuploid in 21 (46%), and aneuploid histograms occurred with equal incidence in either the primary or metastasis in the remaining 24 cases. No statistically significant prediction of survival could be made from any correlation with the histograms of either the primary or metastasis. The potential technical problems and limitations of flow cytometry in the determination of DNA content of formalin-fixed, paraffin-embedded tissue and the selection of patients with advanced disease warrant caution in the interpretation of results.

Carcinoma, Squamous Cell↗
PubMed1995

Previous tonsillectomy as prognostic indicator for success of uvulopalatopharyngoplasty.

Factors that determine a successful outcome following uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea (OSA) are not well defined. This study was undertaken to determine if prior tonsillectomy is predictive of a lower response rate to UPPP. A retrospective review of a cohort undergoing UPPP alone or in combination with nasal septoplasty for OSA was undertaken. Preoperative and postoperative polysomnograms were obtained to evaluate the severity of the OSA. The sample was a consecutive series of 79 patients with OSA. Clinical evaluation was performed by both an otolaryngologist and a pulmonologist. Surgical treatment in this group of 79 patients included 52 UPPP and 27 UPPP in patients with prior tonsillectomy. Concurrent septoplasty was undertaken in 17 patients. Criteria for outcome were based on comparison of preoperative and postoperative polysomnograms (i.e., apnea index, respiratory disturbance index change, and lowest saturation). A response to therapy was defined as a reduction in apnea index greater than 50%. A success was defined as apnea index less than 5, reduction of respiratory disturbance index greater than 50%, and nadir saturation greater than 82%. In 79 patients with OSA, 78% responded and 37% reflected therapeutic successes. Patients with history of prior tonsillectomy were less likely to have therapeutic improvement following UPPP. In 52 patients without previous tonsillectomy, 88% responded and 52% had a successful outcome. Of those with previous tonsillectomy, 59% responded and 7% had a successful outcome. The status of previous tonsillectomy is an important prognostic indicator in the success of UPPP for the treatment of OSA. We speculate that the presence of palatine tonsils allows the removal of an extra measure of oropharyngeal tissue, thereby improving the likelihood of success for UPPP.

Adult↗
PubMed1995

Accuracy of intraoperative staging of the NO neck in squamous cell carcinoma.

Management of the neck in squamous cell carcinoma of the upper aerodigestive tract continues to be a topic of great debate. One major problem is that incorrect clinical staging is expected in approximately 20% of necks. This is true of both clinical stage NO and N+ necks, even when imaging studies are used. This prospective study of 108 necks in 79 patients examined the role of intraoperative palpation and inspection in improving the surgeon's ability to predict nodal stage. Of 62 patients with NO necks clinically on both sides, 26 were staged N+ by intraoperative node examination. Nineteen of the 26 were histologically negative (73% false-positive). Of the 36 patients staged intraoperatively as NO, 10 were histologically positive (28% false-negative). Of 108 necks judged clinically to be NO, 25 (23%) had occult metastases and 11 (10%) had extracapsular spread. Forty-one of 108 clinical NO necks were believed to have positive nodes at the time of neck dissection. Of these 41 necks, 30 (73%) were found to be histologically NO (false-positive). Of the 67 clinical NO necks that were also believed to be NO intraoperatively, occult metastases were found in 14 (21% false-negative). Therefore, intraoperative staging did not significantly improve the false-negative rate. Frozen-section biopsy obtained in the operating room was reliable in 24 (92.3%) of 26 patients. Although frozen-section biopsy was not performed in all patients, these data suggest that upstaging the neck without frozen-section biopsy is much less reliable. This study supports the use of frozen-section biopsy before converting the selective dissection to a radical or modified neck dissection in most instances.

Biopsy↗
PubMed1995

Isoflurane-chlorodifluoroethene interaction in human liver microsomes. Role of cytochrome P4502B6 in potentiation of haloethene metabolism.

Short-chain saturated halocarbons, including isoflurane and the chlorofluorocarbon substitute HCFC-123, can strongly potentiate the cytochrome P450-dependent oxidation of gaseous haloethenes, such as 2-chloro-1,1-difluoroethene (CDE) and vinyl chloride, in vivo and in vitro. P450 isozyme specificity in this effect is suggested by the fact that the interaction is pronounced in microsomes from rats treated with phenobarbital, but does not occur in microsomes of isoniazid- or beta-naphthoflavone-treated animals. We examined the effect of isoflurane on CDE defluorination in liver microsomes from 10 human organ donors to determine whether saturated halocarbon/haloethene interactions also occur in humans and, if so, to determine the cytochromes P450 involved. Three of the samples exhibited isoflurane-stimulated increases (24, 32, and 41%) in CDE defluorination; isoflurane either inhibited or had no effect on CDE metabolism in the other seven samples. Two samples in which isoflurane potentiated CDE metabolism to the greatest rates had higher coumarin 7-hydroxylase (indicative of CYP2A6), 7-ethoxycoumarin O-deethylase (CYP2B6), and nifedipine oxidase (CYP3A4) activities than the other eight samples. However, all 10 subjects had similar rates of phenacetin O-deethylation (CYP1A2) and chlorzoxazone 6-hydroxylation (CYP2E1). In microsomes from cells transfected with cDNAs coding for individual human P450s, CDE metabolism by CYP2B6 was stimulated (216%) by isoflurane, whereas isoflurane did not stimulate CDE metabolism by human CYP2A6, CYP3A4, CYP2D6, or CYP2E1. Isoflurane highly increased CDE defluorination in purified rat CYP2B1 (470%).(ABSTRACT TRUNCATED AT 250 WORDS)

7-Alkoxycoumarin O-Dealkylase↗