Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype.

We have recently shown that HPV-positive tonsillar carcinoma in young patients exhibits nonkeratinizing basaloid morphology and a characteristic immunophenotype. The purpose of this study was to review a large number of cases of oropharyngeal carcinomas, in all age groups, and to identify tumors with nonkeratinizing morphology. Using polymerase chain reaction (PCR) the prevalence and type of HPV DNA was determined in representative cases and in a control group of conventional keratinizing squamous cell carcinomas. The tumors were further characterized with a panel of immunohistochemical stains. A total of 235 carcinomas were reviewed; 141 of the tonsils and 94 in the base of tongue. Ninety (36%) of the tonsillar and 30 (32%) of the base of tongue carcinomas were nonkeratinizing (NKCa) with basal cell features; the rest were classical keratinizing squamous cell carcinomas (KSCC). HPV DNA, particularly type 16, was identified in 10 (100%) of 10 of NKCA and in only 2 (20%) of 10 of KSCC (P = .0014). NKCas were strongly reactive to p16 antibodies while KSCC showed weak and focal reactivity. Higher Ki67 and lower p53 staining scores were observed in NKCa as compared to KSCC. It is concluded that NKCa of the tonsils and base of tongue is a distinct subtype of squamous cell carcinoma of the head and neck with high prevalence of HPV DNA and a characteristic immunophenotype.     

Increased Ventricular Vulnerability in a Chronic Ethanol Model Despite Reduced Electrophysiologic Responses to Catecholamines

An increased incidence of sudden death has been reported in chronic alcoholism. To assess electrical vulnerability of the heart, action potential responses, and the role of the sympathetic system, a well-nourished canine model has been studied intact under chloralose anesthesia after 1 year of ethanol consumption at 36% of caloric intake. Two alcoholic groups were compared with controls (Group 1). In Group 2 myocardial vulnerability was assessed after chronic EtOH and superimposed acute administration. In Group 3 basal vulnerability was related to circulating norepinephrine and release of neurohormone from the myocardium. Subsequently the responsiveness to catecholamine infusion was determined. To assess vulnerability an electrode catheter was placed in the right ventricular apex. The basal ventricular fibrillation threshold (VFT) was reduced to 27 +/- 3 ma in Group 2 versus 43 +/- 1.0 in Group 1. Acute infusion of ethanol in Group 2 further reduced the threshold. Group 3 had a reduced basal VFT. Baseline arterial plasma levels of norepinephrine were 8-fold higher and coronary venous levels 13 times higher in the alcoholic group than in Group 1. However, VFT was not responsive to infused epinephrine, compared with Group 1 controls. In vitro study of superfused ventricular tissue from Group 3 revealed that basal action potential amplitude, overshoot, and resting potential were comparable with normals. Basal repolarization time (90%) was 198 +/- 12 msec in Group 3 versus 215 +/- 6 msec in Group 1 (p less than 0.05). After acute EtOH, repolarization time was shortened to 170 +/- 8.6 in Group 1 at 90 mg% ethanol (p less than 0.002), with minimal further change up to 280 mg%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dengue fever presenting with acute colitis.

Gastrointestinal manifestations of dengue fever are mainly in the form of bleeding or liver function abnormalities. Dengue fever presenting as acute colitis-like picture is not reported to date. We report a 50-year-old man with dengue fever presenting with lower gastrointestinal bleeding and colonoscopic features of acute inflammatory colitis.     

Stereotactic excision of deep brain lesions using probe guided brain retractor

A probe guided brain retractor is described. The capability of it being guided by a probe allows it to be used for stereotactic excision of deep brain lesions. It can also be used with the ultrasound guided probe. Method of use with the stereotactic probe and early surgical experience is presented.     

Characterization of HLA DR3/DQ2 transgenic mice: a potential humanized animal model for autoimmune disease studies

Linkage studies indicate close associations of certain HLA alleles with autoimmune diseases. To better understand how specific HLA alleles are related to disease pathogenesis, we have generated an HLA DR3/DQ2 transgenic mouse utilizing a 550-kb yeast artificial chromosome (YAC) construct containing the complete DRalpha, DRbeta1, DRbeta3, DQalpha, and DQbeta regions. The transgenic mouse (4D1/C2D) in an I-Abeta(o) background appears healthy with no signs of autoimmune diseases. Lymphoid tissues as well as CD4(+) T cells develop normally. Characterization of the transgene expression demonstrates that approximately 90% of B cells express high levels of DR3 and 50-70% of B cells express DQ2. CD11c(+) dendritic cells express high levels of DR and DQ. Approximately 12-18% of resting T cells are positive for DR expression, and further up-regulation to 40-50% expression is seen upon activation with anti-CD3/anti-CD28 mAb. These results suggest that the transgenic construct confers a high fidelity to the normal human temporal and spatial expression profile. Analysis of T cell receptor repertoire in transgenic mice confirms that DR3/DQ2 are able to mediate thymic selection. Furthermore, transgenic mice respond to a DR3-restricted antigen, demonstrating antigen processing and presentation by antigen-presenting cells (APC). Purified T cells from ovalbumin (OVA)-immunized 4D1 mice respond to human APC co-cultured with OVA, suggesting appropriate antigen/DR3 or DQ2 recognition by murine T cells. Immunoglobulin isotype switching is also observed, indicating functional T-B cognate interactions. Thus, the DR3/DQ2 transgenic mouse has normal lymphoid development and functionality that are mediated by HLA transgenes and can be used to investigate HLA-associated immunological questions.     

Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children

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