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Biomedical subjects

J T Johnson

Publications and source records attributed to J T Johnson.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

Assessment of sensitivity and specificity of immunohistochemical staining of p53 in lung and head and neck cancers.

Thirty-two primary carcinomas of the lung and 17 carcinomas of the head and neck (HN) were systematically analyzed for p53 mutations in the highly conserved regions of the gene (exons 5-8). Frozen sections of the same tumors were stained immunohistochemically to assess the sensitivity and specificity of p53 expression as determined by the presence or absence of the protein. On the basis of histology, the lung tumors studied were divided into adenocarcinomas (AC; n = 15), squamous-cell carcinomas (SCC; n = 12), and large-cell carcinomas (LCC; n = 5). All the HN cancers were SCC. Mutations in the p53 gene were detected by direct sequencing of amplified polymerase chain reaction products in six AC of the lungs (40%), three SCC of the lungs (25%), and one LCC (20%), with an overall mutation frequency of 31%. Nine AC (60%) of the lungs, five SCC (42%), and four LCC (80%) were p53-positive by immunohistochemistry. Among HN cancers, p53 mutations were detected in seven tumors (41%). Nine HN tumors (53%) were positive for p53. Negative staining, despite the presence of p53 mutations, was confined to nonsense mutations with truncated p53 and to single-base mutations not causing any change in the amino acid. Although immunohistochemical staining for mutated p53 is sensitive and simple to perform as a screening method, it is not as specific for evaluation of p53 mutations in lung and HN cancers.

Adenocarcinoma↗

The neck mass. A challenging differential diagnosis.

In patients with neck masses, accurate history taking and physical examination often narrow the differential diagnosis tremendously. Diagnostic tests may be helpful but should be done only if management is affected as a result. Fine-needle aspiration, when necessary, is often valuable to obtain a tissue diagnosis, but its accuracy may depend on the experience of the cytopathologist. Antibiotic therapy is sufficient for some inflammatory masses; excision is generally needed for congenital lesions and malignant neoplasms.

Adult↗

The infected wound and its management.

The infected wound is one of the most frequent causes of delayed wound healing. Even in the face of appropriate antibiotic prophylaxis, infections can occur in 10% to 20% of clean-contaminated procedures in the head and neck. The authors describe their comprehensive approach to prevent and manage the infected wound at the head and neck area.

Antibiotic Prophylaxis↗

Tumor angiogenesis as a predictor of tumor aggressiveness and metastatic potential in squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck induces neovascularization to support tumor growth and facilitate the metastatic spread. Others have suggested that the density of microvessels within the tumor correlates with the neovascularization process and therefore with clinical behavior and outcome. To ascertain the value of the microvessel count as an independent prognostic indicator for squamous cel carcinoma of the head and neck, we studied the primary tumors of 44 patients. Histological slides were stained for factor VIII and the individual microvessels were counted on a 200 x field (0.49 mm). No statistically significant difference was found between the microvessel counts of tumors that metastasize or recur locally, as compared with tumors that did not. The possibility of a beta-error due to the small number of cases mandates a larger possibly multi-institutional, study to better ascertain the significance of a microvessel count as an independent prognostic indicator.

Carcinoma, Squamous Cell↗

Variation of p53 mutational spectra between carcinoma of the upper and lower respiratory tract.

Mutations of the p53 tumor suppressor gene are the most common genetic alterations associated with human cancer. Tumor-associated p53 mutations often show characteristic tissue-specific profiles which may infer environmentally induced mutational mechanisms. The p53 mutational frequency and spectrum were determined for 95 carcinomas of the upper and lower respiratory tract (32 lung and 63 upper respiratory tract). Mutations were identified at a frequency of 30% in upper respiratory tract (URT) tumors and 31% in lung tumors. All 29 identified mutations were single-base substitutions. Comparison of the frequency of specific base substitutions between lung and URT showed a striking difference. Transitions occurred at a frequency of 68% in URT, but only 30% in lung. Mutations involving G:C-->A:T transitions, which are commonly reported in gastric and esophageal tumors, were the most frequently identified alteration in URT (11/19). Mutations involving G:C-->T:A transversions, which were relatively common in lung tumors (3/10) and are representative of tobacco smoke-induced mutations were rare in URT tumors (1/19). Interestingly, G:C-->A:T mutations at CpG sites, which are characteristic of endogenous processes, were observed frequently in URT tumors (9/19) but only rarely in lung tumors (1/10), suggesting that both endogenous and exogenous factors are responsible for the observed differences in mutational spectra between the upper and lower respiratory systems.

Alcohol Drinking↗

HLA restriction and T-cell-receptor V beta gene expression of cytotoxic T lymphocytes reactive with human squamous-cell carcinoma of the head and neck.

A human cytotoxic-T-lymphocyte (CTL) line capable of killing autologous tumor (AuTu) cell targets was established from peripheral-blood lymphocytes of a patient with squamous-cell carcinoma of the tongue. The cultured CTL were CD3+CD8+CD11b-HLA-DR+T cell receptor (TCR) alpha/beta+. When tested in 4-hr 51Cr-release assays against various lines of squamous-cell carcinoma of the head and neck (SCCHN) and a variety of non-squamous human tumor and normal cell targets, the CTL were found to lyse the autologous SCCHN cell line (PCI-50) and 7 allogeneic SCCHN lines: PCI-1, -2, -4A, -4B, -13, -30 and -38. Of these tumor cell lines, PCI-13, -30 and -38 shared HLA-A2 locus with the AuTu, PCI-50, while PCI-4A and -4B shared HLA-B44 with AuTu. Lysis of AuTu (A2+B44+), PCI-13 (A2+B44-) and PCI-4B (A2- B44+) by the CTL was efficiently inhibited by monoclonal antibodies (MAbs) to CD3, CD8, TCR alpha/beta or the major-histocompatibility-complex (MHC)-class-I antigens. MAbs to HLA-A2 antigens inhibited lysis of PCI-50 or PCI-13 targets by the CTL. In cold-target inhibition assays, unlabeled PCI-4B or PCI-13 cells inhibited CTL lysis of AuTu targets. The CTL incubated in the presence of the HLA-A2+ SCCHN PCI-50 or -13, but not an HLA-A2+ gastric carcinoma, produced TNF-alpha, IFN-gamma and GM-CSF. The CTL were tested for their TCR V beta gene expression by polymerase chain reaction (PCR). At week 10 in culture, the time of the highest AuTu cytotoxicity mediated by the CTL line, V beta 6 was expressed by 26% of T cells. Three clones, obtained by limiting dilution from 10-week CTL and selected for high cytotoxicity against AuTu, were found to be V beta6+. Further analysis of the specificity of these clones indicated lytic activity against PCI-13 (A2+B44-), but not PCI-4B (A2-B44+) targets. In 16-week cultures, which retained AuTu cytotoxicity as well as V beta 6 expression, TCR V beta 2 was also expressed at high frequency (29%), and AuTu-reactive clones were found to be V beta 2+. Our results indicate that at least 2 different CTL populations (V beta 6+ and V beta 2+) are able to recognize SCCHN-associated antigen(s) and that the V beta 6+ T cells are HLA-A2 restricted, while V beta 2+ T cells may be HLA-B44 restricted.

Antibodies, Monoclonal↗

The impact of bilateral neck dissection on pattern of recurrence and survival in supraglottic carcinoma.

OBJECTIVE: The findings of an initial evaluation of 202 patients treated for squamous cell carcinoma of the supraglottic larynx have been previously reported. Recurrent disease was observed at the primary site in four patients (2%), in the regional lymphatics in 39 patients (20%), and at distant sites in 24 patients (12%). Critical analysis of patients who demonstrated recurrent disease in the cervical lymphatics indicated that 38 of 39 recurrences developed in nonsurgically treated necks irrespective of the use of postoperative radiation therapy. Accordingly, all patients with supraglottic carcinoma have been treated with routine bilateral neck dissection since that time. We have reviewed our data to determine if bilateral neck dissections deter recurrence and improves survival. DESIGN: A retrospective review of the clinical course of 76 patients undergoing excision of supraglottic squamous carcinoma combined with bilateral neck dissection between 1980 and 1990 was performed to determine survival and recurrence rates. Surgery alone was used to treat 32 patients, while 44 patients were treated with surgery plus adjunctive therapy. SETTING: Department of Otolaryngology--Head and Neck Surgery, The Eye and Ear Institute, University of Pittsburgh (Pa) School of Medicine. RESULTS: Distant metastatic spread was the most frequent site of failure, occurring in nine (11.8%) of 76 patients. Local recurrence was experienced by two patients (1%). The incidence of cervical recurrence (seven patients, 9.2%) following treatment for squamous cell carcinoma of the supraglottic larynx has been reduced from 20% to 9% through the use of bilateral neck dissection. The 2-year survival rate increased from 72% to 76%. CONCLUSION: Routine bilateral neck dissection is beneficial in the surgical management of squamous cell carcinoma of the supraglottic larynx.

Adult↗

In vitro urokinase type plasminogen activator levels and total plasminogen activator activity in squamous cell carcinomas of the head and neck.

OBJECTIVE: Determine total plasminogen activator (PA) activity and urokinase-type plasminogen activator (u-PA) levels in cell-free supernatants derived from primary and metastatic squamous cell carcinoma of the head and neck. DESIGN: Plasminogen activator activity was measured by spectrophotometric assay with chromogenic substrate Val-Leu-Lys-para-nitroanilide. Urokinase-type plasminogen activator levels were measured with enzyme-linked immunosorbent assay technique. RESULTS: Fourteen established squamous cell carcinoma lines from patients with head and neck cancer were assayed for both total PA activity and u-PA levels at 24 to 48 hours of incubation. Compared with control and fibroblast-conditioned media, cell lines established from squamous cell carcinoma of the head and neck had significantly (P < .005) higher levels of both total PA activity and u-PA levels. Linear regression analysis showed a positive correlation (r = .65, P = .007) between total PA activity and u-PA levels. CONCLUSIONS: Squamous cell carcinomas of the head and neck are able to activate plasminogen and produce u-PA in vitro. The production of PA by squamous cell carcinomas of the head and neck may play an important role in the biology of invasion and metastasis.

Carcinoma, Squamous Cell↗

Role of skull base surgery for local control of sarcoma of the nasal cavity and paranasal sinuses.

Sarcomas of the nose and paranasal sinuses are rare neoplasms and comprise less than 1% of the malignancies arising in the sinonasal tract. From 1977 to 1989, we had the opportunity to treat 15 patients presenting with these tumors at The Eye & Ear Institute of the University of Pittsburgh. The clinical charts of these patients were reviewed retrospectively for demographic data, characteristics of disease, treatment considerations and clinical outcome. Data were also analyzed with special attention to the role of skull base surgery for the local control of tumors. Seven patients underwent cranial base surgery as part of their original therapy. Two of these patients are alive with no evidence of disease, one patient died of other causes, and four are dead of disease. Two patients died with local disease. Although not statistically significant due to the small number of patients, these data suggest that cranial base surgery can improve the local control of sarcomas of the sinonasal tract that approach or invade the skull base.

Adolescent↗

Circulating markers in squamous cell carcinoma of the head and neck: a review.

Biological markers of disease enhance the ability to diagnose, treat and evaluate results of therapy and are especially intriguing for their potential use in the management of malignant tumours. The serum levels of various biochemical substances have been shown to be abnormal for many cancers and are utilised in the management of affected patients. Several markers have been thoroughly investigated for potential clinical utility in head and neck carcinoma. Although no single marker has been found to be adequately sensitive and specific, combinations of markers may improve the utility for some aspects of patient management. This review highlights the literature to date in the realm of circulating markers for head and neck carcinoma. A discussion of the potential usefulness and limitations of such markers follows.

Antigens, Neoplasm↗