Neel, H. Bryan

Normal human squamous mucosal cells of the soft palate, buccal surface, epiglottis, hypopharynx, floor of the mouth, and tongue were cultured in vitro in serum-free medium. In medium MCDB 153 containing epidermal growth factor, insulin, bovine pituitary extract, and 0.1 or 2.0 mmol/L Ca ** , squamous mucosal cells double every 24 hours. These cells then can be induced to arrest their proliferation reversibly by treatment with transforming growth factor-β or ethionine, and they can irreversibly growth-arrest during senescence or when cultured in growth factor–deficient medium containing 2 mmol/L Ca ** . The latter medium also induces differentiation, as does culture of cells in serum-containing medium. Serum-containing medium furthermore promotes extensive cell stratification and the formation of multilayered squamous mucosal tissue specimens that can be removed intact by Dispase treatment. These specimens represent potential autogenous mucosal grafts that can be used in patients who require reconstructive surgery of the oral cavity and oropharynx. Normal human squamous mucosal cells therefore closely resemble keratinocytes derived from the epidermis in the mechanisms that regulate proliferation and differentiation. This model cell system should facilitate future studies on upper aerodigestive tract squamous mucosal cell physiology and pathophysiology.

Natural killing (NK) may play an important role in immunosurveillance against virus‐infected and malignant cells. This study has demonstrated that the NK susceptibility of Epstein‐Barr virus (EBV)‐related cell lines increases with increased viral expression within the cells. This finding has implications for surveillance against, and treatment of, EBV‐related disease. Additionally, preliminary studies of the NK status of head and neck cancer patients reveal a distinct clustering of the patients into either groups of high or low NK reactivity. This clustering phenomenon may have a correlation with patient prognosis.

Because antibody titers against Epstein‐Barr virus (EBV) antigens often are elevated in patients with active undifferentiated and nonkeratinizing nasopharyngeal carcinoma, anti‐EBV serologic tests have been applied as a diagnostic aid in patients who have metastatic lymphadenopathy in the neck without an obvious source. In this study of 44 patients, the serologic testing procedure proved useful in identifying six patients with nasopharyngeal carcinoma that was initially occult but was eventually confirmed by biopsy.

The Epstein‐Barr virus (EBV) is closely associated with nasopharyngeal carcinoma, suggesting an etiologic relationship. We have undertaken studies (1) to quantitate the relationship between antibody titers to EBV‐associated antigens and nasopharyngeal carcinoma in American patients since most of the patients in previous studies were of either Asian or African descent and (2) to determine the relationship between antibody titers and the clinical course of disease. Sera from patients with primary or recurrent nasopharyngeal carcinoma and from patients in remission, from patients with various other head and neck tumors (including occult primary lesions and lymphomas), and from normal controls were titrated for IgG antibodies to viral capsid antigen (VCA) and early antigen and IgA antibodies to VCA, using indirect immunofluorescence procedures previously detailed. High titers of antibodies to EBV‐induced early antigen and VCA in the IgG fraction and VCA in the IgA fraction were frequently found in the sera of patients with nasopharyngeal carcinoma. A significant reduction in these titers was observed with clinical remission of the disease in treated patients. Preliminary findings suggest that EBV serology may be useful in the evaluation and treatment of patients with nasopharyngeal carcinoma and also in patients with cervical metastases from clinically occult primary sites in order to identify those with occult nasopharyngeal carcinoma.

The tetrad of bronchial asthma, nasal disease, eosinophilia, and systemic vasculitis is the main feature of allergic granulomatosis and angiitis. Twenty‐two of 32 patients (69%) with this disorder had nasal manifestations, including nasal polyps, thick crusts, rhinitis, sinusitis, and occasionally septal perforations. Histopathologic study of involved tissue from the nose or subcutaneous nodules in conjunction with clinical evaluation will aid in establishing the correct diagnosis. Treatment with corticosteroids favorably influences symptoms and prognosis.

At the Mayo Clinic from 1962 to 1974, 182 patients with early squamous cell cancer of the true vocal cord were treated by laryngofissure and cordectomy. Seven patients (4%) had recurrences: four in the larynx and three in the neck (although the larynx was free of disease). The case histories of these patients are reported. Only three (2%) of the patients died as a consequence of their laryngeal cancer. The data substantiate our belief that the laryngofissure and cordectomy operation, and its minor variations, is an expeditious and highly successful means of eradicating glottic cancers.

Numbers and percentages of T and B cells in peripheral blood; blastogenic responses to PHA, Con A, and PWM; and serum levels of albumin, total protein, and IgA were assessed in patients with stages I to III operable squamous cell carcinoma of the upper aerodigestive passageways in the head and neck.The patients were categorized into two groups: those who remained tumor free and those in whom cancer recurred. It was found that pretreatment PHA‐ and Con A‐induced blastogenesis was often depressed in patients in whom clinically apparent recurrences developed regardless of stage or nodal involvement. This point is consistent with the idea that cellular immune function (blastogenesis) can identify, within the clinical staging system (TN), subpopulations of patients who are less likely to survive after conventional therapy.

IgA immunoglobulin fractions containing antibodies to Epstein‐Barr virus (EBV)‐induced membrane antigens were isolated from the sera of two patients with nasopharyngeal carcinoma (NPC), from one non‐NPC patient, and from three persons with sera negative for IgA antibodies. IgA antibodies were not cytotoxic against cells expressing EBV‐induced membrane antigens in the antibody‐dependent cellular cytotoxicity (ADCC) assay. However, IgA antibodies blocked IgG‐mediated ADCC, which indicated that these antibodies could serve as a blocking “factor” in patients with disease and, therefore, were potentially detrimental to the host.