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Biomedical subjects

D Greenspan

Publications and source records attributed to D Greenspan.

At least 109 records · Page 6Linked to original sources

Subcellular distribution and life cycle of Epstein-Barr virus in keratinocytes of oral hairy leukoplakia.

The authors investigated the life cycle of Epstein-Barr virus (EBV) in keratinocytes of oral hairy leukoplakia by combining immunohistochemistry. DNA in situ hybridization, and lectin histochemistry with electron microscopy. Diffuse-staining components of the EBV early antigen complex (EA-D), EBV 150-kd capsid antigen (VCA), EBV membrane antigen (gp350/220), and double-stranded DNA were labeled with monoclonal antibodies. An EBV-DNA probe was used to locate EBV DNA. Wheat-germ agglutinin (WGA) was employed to distinguish Golgi-associated compartments. The authors found EBV proteins and EBV DNA only in keratinocytes with apparent viral assembly. In situ hybridization showed EBV DNA in free corelike material and in electron-dense cores of mature nucleocapsids. Monoclonal antibodies to nonspecific double-stranded DNA attached to the same structures and to marginated chromatin. Components of EA-D were dispersed throughout the nuclei but accumulated near condensed chromatin and in 'punched-out' regions of the chromatin. Epstein-Barr virus 150-kd capsid antigen was found only in the nuclei, where it appeared preferentially on mature nucleocapsids. As yet unexplained arrays of intranuclear particles that remained unlabeled with all EBV-specific probes reacted intensely with an antiserum against common papillomavirus antigen. Gp350/220 was detectable in various cellular membrane compartments and was highly concentrated on EBV envelopes in peripheral Golgi-associated secretory vesicles. It was less abundant on the extracellular EBV, indicating that viral membrane antigen partly dissociates from the mature virus. Combined lectin-binding histochemistry and electron microscopy demonstrated for the first time that EBV is processed in the Golgi apparatus, which eventually releases the virus by fusion with the plasma membrane. These results provide insight into the biologic events that occur during complete EBV replication in vivo.

Adult↗

Oral candidiasis in HIV infection: pseudomembranous and erythematous candidiasis show similar rates of progression to AIDS.

Candidiasis is the most common oral fungal infection seen in association with HIV infection. It may present in a number of clinical forms, including pseudomembranous and erythematous candidiasis. To determine whether erythematous candidiasis, like the pseudomembranous form, is predictive of the development of AIDS, we reviewed the records of 169 HIV-seropositive patients seen at clinic of the Oral AIDS Center, University of California, San Francisco who were diagnosed with pseudomembranous or erythematous (or both) forms of oral candidiasis at their first examination. Kaplan-Meier analysis showed a rapid rate of progression to AIDS (median, 25 months) and to death (median, 43.8 months) in all three groups. We conclude that erythematous candidiasis is as serious a prognostic indicator as pseudomembranous candidiasis. Because the erythematous form is more difficult to recognize and hence is underdiagnosed, efforts should be made to teach non-dental clinicians who care for HIV-infected patients to diagnose and treat this lesion.

Acquired Immunodeficiency Syndrome↗

Oral manifestations of HIV infection.

Oral lesions are frequently seen in association with all stages of infection with the human immunodeficiency virus (HIV). Many of these lesions occur as the first clinical sign of HIV infection. These lesions include candidiasis, hairy leukoplakia, warts, ulcers, and an aggressive form of periodontal disease. Careful oral examination may reveal lesions that alter Centers for Disease Control staging.

Acquired Immunodeficiency Syndrome↗

Risk factors for rapid progression from hairy leukoplakia to AIDS: a nested case-control study.

To determine risk factors for early progression from oral hairy leukoplakia to AIDS, this case-control study compared 27 patients who had not progressed to AIDS within 1,000 days of diagnosis of hairy leukoplakia with 28 patients who progressed rapidly. The risk factors that proved most predictive fell into two categories: (a) those reflecting sexual practices that correlated with how early in the epidemic patients were likely to have been infected, and (b) those reflecting immune competence. Hepatitis B was associated with a fourfold risk for early progression and syphilis with a nearly threefold risk. Skin test anergy for Candida species was strikingly predictive: all of 17 tested in the early progression group were anergic, compared with only two of 12 tested in the late progression group. Although skin testing has been largely supplanted by assessment of T-cell subsets, Candida species skin testing may be of particular prognostic value in otherwise apparently healthy HIV-infected persons.

Acquired Immunodeficiency Syndrome↗

Frequent isolation of HHV-6 from saliva and high seroprevalence of the virus in the population.

Human herpesvirus-6 (HHV-6) was recovered at high frequency (greater than 85%) from the saliva of both healthy individuals and those infected with the human immunodeficiency virus (HIV). The level of isolation mirrored the high prevalence of antibodies to HHV-6 found in sera obtained from residents of diverse areas of the world. Seroconversion occurred between 1 and 3 years of age; seroprevalence ranged between 80% and 100% among adults under 40 and decreased to 35% between ages 62 and 88. Serum titres in healthy individuals remained stable during periods of virus shedding. Immune cellular dysfunction in patients was associated with high geometric mean HHV-6 antibody titres. These observations suggest that HHV-6 infection takes place within the first 3 years of life, and strongly implicate oral shedding as a common means of transmission of this newly described herpesvirus.

Acquired Immunodeficiency Syndrome↗

Diagnosis of Epstein-Barr virus infection in hairy leukoplakia by using nucleic acid hybridization and noninvasive techniques.

The presence of Epstein-Barr virus (EBV) DNA in the epithelial cells of oral hairy leukoplakia is the confirming criterion in the diagnosis of this lesion, which occurs mainly in persons infected by the human immunodeficiency virus. Because hairy leukoplakia often presages the development of the acquired immune deficiency syndrome, it is important that suspicious lesions be accurately diagnosed. Commonly, biopsy tissue is removed for detection of EBV DNA by in situ hybridization, but biopsy is contraindicated in some patients. This study evaluated filter and cytospin in situ hybridization, two noninvasive techniques that examine epithelial cells swabbed from the surfaces of the lesions, for their sensitivity in detecting EBV DNA. As compared with tissue in situ hybridization, the filter and cytospin techniques had sensitivities of 100 and 92%, respectively. We conclude that these two noninvasive techniques can provide the clinician with an accurate alternative to biopsy whenever this human immunodeficiency virus-associated lesion is suspected.

Evaluation Studies as Topic↗

Oral mucosal lesions found in smokeless tobacco users.

The risk for oral mucosal lesions associated with use of smokeless tobacco among 1,109 professional baseball players during spring training in 1988 was investigated. Leukoplakia was very strongly associated with use of smokeless tobacco in this population of healthy young men. Of the 423 current smokeless tobacco users, 196 had leukoplakia compared to seven of the 493 nonusers (OR = 60.0, 95% CI = 40.5-88.8). The amount of smokeless tobacco used (in hours per day that smokeless tobacco was held in the mouth), recency of smokeless tobacco use (hours since last use), type (snuff versus chewing tobacco), and brand of snuff used were significantly associated with risk for leukoplakic lesions among smokeless tobacco users. Ninety-eight leukoplakic areas in 92 subjects were biopsied and examined microscopically. All lesions were benign, but one specimen had mild epithelial dysplasia. The long-term significance of leukoplakia in smokeless tobacco users and their relation to oral cancer is not clear.

Adult↗

Efficacy of desciclovir in the treatment of Epstein-Barr virus infection in oral hairy leukoplakia.

The efficacy of desciclovir, an analog of acyclovir, in eliminating lesions of oral hairy leukoplakia (HL) and suppressing Epstein-Barr virus (EBV) infection was evaluated in a double-blind, placebo-controlled study of 14 patients. Patients were randomized to receive either the active drug, 250 mg three times a day for 14 days, or placebo. In all eight patients receiving desciclovir, lesions of HL were either completely resolved or significantly reduced during the treatment period, whereas lesions in patients receiving placebo showed no change. The histological features of HL were significantly diminished in patients on desciclovir, and cytochemical, in situ hybridization, and ultrastructural studies showed that EBV infection was eliminated or dramatically reduced in the desciclovir group only. Four patients on desciclovir reported side effects, but none required withdrawal from the study. The reappearance of HL in all eight subjects on desciclovir within 1-4 months after therapy was discontinued suggests the need for additional study.

Acyclovir↗

Oral complications of cancer therapies. Management of salivary dysfunction.

Xerostomia is a common complication of radiation therapy to the head and neck. In such cases, the symptom is often permanent and leads to difficulty in mastication, wearing dentures, deglutition, and speaking. Other side effects include candidiasis and caries. Therapy is for the most part symptomatic and empirical. However, the use of sialogogues shows promise. Effective salivary substitutes and sialogogues that have minimal side effects need to be developed.

Head and Neck Neoplasms↗

Granuloma annulare of the buccal mucosa in association with AIDS.

This case report describes the occurrence of a lesion of granuloma annulare in the buccal mucosa. This skin condition occurs rarely on the mucous membranes and has not been previously described in the oral cavity. It was initially seen as a raised, firm lesion with a 1-month history in a 31-year-old patient with acquired immune deficiency.

Acquired Immunodeficiency Syndrome↗

Oral hairy leukoplakia: diagnosis and management.

Oral hairy leukoplakia (HL) is a remarkable lesion associated with Epstein-Barr virus (EBV) found in persons infected with the human immunodeficiency virus. The clinical and histologic features of HL are characteristic and distinctive. However, none of these features are entirely specific for HL, and we consider that the presence of EBV is required for diagnosis in questionable cases. EBV can be demonstrated by means of electron microscopy, immunocytochemistry, or molecular biologic techniques. Therapy directed toward the HL lesion is sometimes indicated; acyclovir is the current drug of preference in such cases.

Acquired Immunodeficiency Syndrome↗

Oral hairy leukoplakia with extensive oral mucosal involvement. Report of two cases.

Oral hairy leukoplakia (HL) is a lesion that occurs predominantly on the tongue in HIV-infected persons. Evidence strongly indicates that HL is related to the presence of Epstein-Barr virus in the epithelial cells. The lesion appears on the lateral border of the tongue as a painless, white plaque varying in size from a few millimeters to extensive lingual involvement. Histopathologically, the characteristic findings are hyperparakeratosis, hyperplasia, and ballooning of prickle cells resembling koilocytosis. HL is now considered a frequent, early, and specific sign of HIV infection and a strong indicator that AIDS will develop in the patient. We report on two cases of HL with marked oral mucosal involvement with extension to the pharyngeal mucosa.

Adult↗

Oral lesions mimicking hairy leukoplakia: a diagnostic dilemma.

Oral hairy leukoplakia is seen in immunosuppressed persons infected with the human immunodeficiency virus and is a predictor of the development of acquired immunodeficiency syndrome in that population. Over the past 3 years we have seen 16 examples of a lesion that histologically resembles hairy leukoplakia but is found in patients who are not in risk groups for acquired immunodeficiency syndrome. All these specimens tested negative for Epstein-Barr virus DNA and for human papillomavirus antigen. Sera from five of the 16 patients were tested for antibodies to human immunodeficiency virus, and all results were negative. These findings suggest that the diagnosis of hairy leukoplakia cannot be based on histologic criteria alone but should be verified by DNA in situ hybridization for Epstein-Barr virus.

Adolescent↗

Acyclovir-resistant, foscarnet-sensitive oral herpes simplex type 2 lesion in a patient with AIDS.

We report the case of an immunocompromised patient with AIDS in whom developed a perioral and several intraoral HSV 2 lesions that persisted for more than 1 year. The virus was resistant to acyclovir but was sensitive to foscarnet. Viral isolates were thymidine kinase negative. The lesions resolved with intravenous foscarnet therapy given over a 15-week period, and when last seen, 8 months after foscarnet was discontinued, the patient had not had a recurrence.

Acquired Immunodeficiency Syndrome↗

Parotid gland enlargement and xerostomia associated with labial sialadenitis in HIV-infected patients.

Infection with human immunodeficiency virus (HIV) may be associated with enlargement of the major salivary glands or symptoms of dry mouth. We term this condition HIV-associated salivary gland disease (HIV-SGD). In this report we describe 12 patients with HIV-SGD. Nine patients (one child, eight adults) had enlargement of the parotid glands, and three had xerostomia alone. Symptoms of dry mouth, dry eyes or arthralgia occurred in 11, five and five patients, respectively. Salivary flow rates were normal or slightly reduced in seven patients and severely reduced in five. Labial salivary gland (LSG) biopsy specimens from patients contained lymphocytic infiltrates in focal and other patterns, whereas specimens from three HIV-infected patients without salivary gland symptoms did not. The inflammatory infiltrates in LSG specimens showed a preponderance of T8-positive cells and a tissue T4/T8 average ratio of 0.66. The mean T4/T8 ratio of peripheral blood lymphocytes was 0.4. Serum antinuclear antibodies were present in one patient, but rheumatoid factor, SS-A, and SS-B antibodies were absent in all. Search for Epstein-Barr virus and cytomegalovirus in the LSG tissue of the six patients tested did not reveal evidence of antigens or DNA. HIV-SGD patients show a number of similarities to and differences from patients with Sjögren's syndrome (SS). The similarities include the oral and salivary features, histopathology and possibly changes in other organs. The differences include the lower salivary gland T4/T8 ratio and the absence of autoantibodies in serum. The causes of HIV-SGD as well as of Sjögren's syndrome are unknown.

Adult↗