Carl M. Allen

Restraint stress differentially affects anti-viral cellular and humoral immune responses in mice

Physical restraint administered to C57BL/6 mice significantly altered the inflammatory response to influenza virus infection and depressed anti-viral cellular immunity. Restraint-stressed animals showed a pattern of reduced mononuclear cell infiltration and lung consolidation which coincided with elevated plasma corticosterone levels. Furthermore, cellular immunity to virus was significantly depressed; interleukin-2 secretion was reduced by 96% and 59% in the mediastinal lymph nodes and spleens, respectively, as compared to a non-restrained group. However, the magnitude of the humoral immune response to influenza virus was unaffected by restraint stress. Anti-viral IgG antibody levels in restrained/infected mice did not differ when compared to a non-restrained/infected control group 14 days post-infection.

Oral plasmablastic lymphomas in AIDS patients are associated with human herpesvirus 8.

Human herpes virus type 8 (HHV8) has been strongly associated with Kaposi sarcoma, primary effusion lymphoma (PEL), and Castlemans disease. To our knowledge, infection by this virus has not been strongly associated with other hematopathologic malignancies. We examined five oral cavity lymphomas from men with AIDS for HHV8 and HIV-1 by reverse transcriptase in situ polymerase chain reaction, as well as for Epstein-Barr virus (EBV) (EBER-1, -2) using in situ hybridization and HHV8 protein with immunohistochemistry. Four of these tumors were plasmablastic lymphomas; the final case was diffuse large B-cell lymphoma. Most of the neoplastic cells in these five lymphomas contained HHV8 RNA and protein. Further, the four plasmablastic lymphoma cases had tumor cells that contained EBV. HIV-1 RNA was not detected in the tumor cells but was noted in surrounding benign T cells. In comparison, HHV8 RNA was not detected in any of the five oral cavity lymphomas from people who did not have acquired immunosuppression nor in five lymphomas from AIDS patients that were located at a site other than the oral cavity. It is concluded that oral cavity lymphomas from people with AIDS are strongly associated with infection by HHV8 and EBV. Given the poor prognosis of oral cavity lymphomas in immunocompromised patients, therapy directed against the HHV8 and EBV infection may be of therapeutic value.

Essential Role of the Candida albicans Transglutaminase Substrate, Hyphal Wall Protein 1, in Lethal Oroesophageal Candidiasis in Immunodeficient Mice

Oroesophageal candidiasis is caused by the combined action of fungal virulence factors and host inflammatory responses when protective immunity is absent. Hyphal wall protein 1 (Hwp1) on germ tubes and true hyphae of Candida albicans forms covalent cross-links to buccal epithelial cells in vitro by functioning as a substrate for mammalian transglutaminases. In this study, beige-athymic (bg/bg-nu/nu) or transgenic epsilon 26 mice that have combined natural killer and T cell defects did not succumb to candidiasis after oral administration of C. albicans strains with inactivated HWP1 genes, whereas mice given isogenic strains of C. albicans that had a single copy of HWP1 survived only 2-3 weeks. Illness correlated with extensive alterations of the lingual and esophageal mucosa that were absent in mice given the hwp1/hwp1 mutant. HWP1 is a promising target for development of antifungal drugs for treatment of oroesophageal candidiasis.

Relation of stress and anxiety to oral lichen planus.

Stress and anxiety have frequently been mentioned as possible factors related to the development of oral lichen planus, although this association appears to have only an anecdotal origin. In this study, 48 patients with a clinical and histologic diagnosis of oral lichen planus completed questionnaires aimed at assessing their stressful life events (Social Readjustment Rating Scale) and their tendency for anxiety (the trait portion of the State-Trait Anxiety Inventory). Age- and sex-matched control groups included patients who underwent biopsies for irritation fibroma and routine clinic patients. No significant differences were seen among any of the groups with respect to scores on the questionnaires. These results suggest that patients who manifest oral lichen planus have no greater tendency toward anxiety and no more stressful life events than other individuals.

Plexiform schwannoma: a clinicopathologic overview with emphasis on the head and neck region

Plexiform schwannoma is a rare variant of Schwann cell tumor. Occurring in either conventional or cellular type, they are characterized either grossly or histologically by a plexiform pattern of intraneural growth often with multinodularity. Ordinary as well as plexiform schwannoma typically arise in superficial soft tissues and show a predilection for the head and neck region. Infrequent examples arise in the setting of neurofibromatosis type 2 or schwannomatosis. The purpose of this study was to assess the frequency of plexiform schwannoma by location, to determine their syndromic association, and to analyze the clinicopathologic features of tumors affecting the head and neck region. It was found, in this not entirely random population, that plexiform schwannoma represented 4.3% of all schwannomas, 23% of head and neck region examples, 15% of cutaneous schwannomas, and lastly, 2% of 322 oral nerve sheath tumors made separately available for review. Furthermore, the association with neurofibromatosis type 2 and with schwannomatosis was 5% each.

Immunoglobulin gene rearrangements in lymphoplasmacytic infiltrates of labial salivary glands in Sjögren's syndrome. A possible predictor of lymphoma development.

OBJECTIVES Sjögrens syndrome is an autoimmune disorder in which patients have a well-recognized risk of developing malignant lymphoma. Although some clinical parameters may herald the onset of lymphoma, few reliable histologic or molecular markers are available that predict progression to a malignant lymphoproliferative disorder. The purpose of this study was to identify the prevalence of immunoglobulin heavy chain monoclonality in labial gland biopsies of patients with Sjögrens syndrome and to compare this to clinical outcome. STUDY DESIGN The polymerase chain reaction was applied to 76 sequential labial salivary gland biopsies from patients under investigation for Sjögrens syndrome. A seminested polymerase chain reaction technique was used on DNA extracted from formalin-fixed, paraffin-embedded tissue to amplify the V-D-J region of the immunoglobulin heavy chain gene. Thirty-four randomly selected labial salivary glands that showed nonspecific sialadenitis from patients without Sjögrens syndrome were used as controls. RESULTS Monoclonality, as defined by a single band on polyacrylamide gel electrophoresis was detected in 11 cases (14.5%). Of cases that showed monoclonality, four patients were subsequently diagnosed with extrasalivary lymphoma. In each case the rearranged bands in the lip biopsy and the lymphoma were the same size. In one patient who later developed lymphoma, a monoclonal rearranged immunoglobulin band was not identified. In addition, no cases of the translocation t(14;18) were identified by polymerase chain reaction in any of the lip biopsies showing heavy chain monoclonality or in any of the extrasalivary gland lymphomas. CONCLUSIONS These results suggest that monoclonal immunoglobulin heavy chain gene rearrangements are a relatively common finding in patients with Sjögrens syndrome and may prove to be a useful marker for predicting the progression to, and early detection of malignant lymphoma.

Treatment of oral erosive lichen planus with systemic isotretinoin

Six patients with symptomatic oral erosive lichen planus were treated with systemic isotretinoin (10 to 60 mg daily) for 8 weeks. Five (83%) showed subjective and objective improvement at completion of therapy, but the improvement was slight. Relapse occurred in four patients within 2 months after the drug was stopped; one was lost to follow-up. Because of the minimal improvement and adverse side effects, no patient wished to be re-treated with isotretinoin.

Animal models of oral candidiasis : a review

Candida albicans is the most common fungal infection of the human oral mucosa, yet much remains to be understood with respect to the pathogenesis of the disease. Numerous difficulties are inherent in designing studies that use human beings as subjects. The use of various animal species in experimental contexts has helped to provide insight with respect to this condition. A variety of manipulations of the system can be performed, including altering the host immune response, the mucosal environment, or the systemic environment. In addition, organism-related factors can be examined in a more controlled setting. The information obtained from such studies could not be obtained in an in vitro situation.

Paraneoplastic pemphigus : a distinct autoimmune vesiculobullous disorder associated with neoplasia

A vesiculobullous disease termed paraneoplastic pemphigus with distinct autoantibodies was newly described in 1990. All reported cases have occurred in patients with a history of neoplasia, including lymphoma, chronic lymphocytic leukemia, poorly differentiated sarcoma, and benign thymoma. As in pemphigus vulgaris, intraepithelial clefts with acantholysis are noted histopathologically, and intercellular binding of immunoreactants is seen with direct immunofluorescence studies of mucous membrane and skin biopsies. However, immunoreactants may also be found along the basement membrane zone in paraneoplastic pemphigus. Indirect immunofluorescence using rat bladder epithelium as substrate shows an intercellular pattern that appears to be highly specific for paraneoplastic pemphigus. We report a patient with non-Hodgkins lymphoma of 8 years duration who developed severe erosive stomatitis and lichenoid dermatitis after receiving chemotherapy for a relapse of lymphoma. Her case illustrates the typical features of the disorder described as paraneoplastic pemphigus. Neoplasia-associated pemphigus may be a more precise term for this disorder because the course of the blistering eruption does not always parallel the course of the underlying cancer. The clinical features, histopathologic findings, and immunofluorescence findings of this unique syndrome are reviewed.

Macrognathia of renal osteodystrophy in dialysis patients

A multiinstitutional study of macrognathia secondary to renal osteodystrophy in dialysis patients is presented. The nine cases reviewed reveal a variety of radiographic and histopathologic features, some of which resemble fibrous dysplasia and others suggestive of Pagets disease of bone. This article contains diagnostic criteria for differentiating renal osteodystrophy from similar fibro-osseous proliferations along with a discussion of the underlying cause and appropriate therapeutic interventions.