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[Uterine cervical carcinoma and human papillomaviruses].

For many years it has been thought that a significant proportion of cervical cancer could be attributed to sexually transmitted agents, such as sperm, smegma, Treponema pallidum, Gonococcus and herpes simplexvirus type 2. Recent advances of molecular biology, however, have revealed that human papillomavirus (HPV) might be the most causative virus of the disease. Since HPV type 16 DNA was found in a patient with cervical cancer in 1983, many HPV types have been cloned from cervical cancers, also from premalignant lesions (intraepithelial neoplasias). In Japan, we have found 6 new types of HPV (HPV 58, 59, 61, 62, 64, 67) in the female genital tract so far. Especially, HPV 58, which was cloned from a patient with cervical squamous cell carcinoma and was already fully sequenced, is thought to be an important agent for the development of cervical cancer as well as HPV 16. Now we are investigating extensively to clarify the real relationship between genital HPV infection and cervical cancer.

Animals

Eczema herpeticum. Treatment with methylene blue and light.

Kaposi varicelliform eruption due to herpes simplex virus (eczema herpeticum) is a serious disease in infants, with occasional fatal outcome. Photoinactivation therapy consisting of local application of methylene blue followed by light exposure resulted in rapid improvement both clinically and virologically. Methylene blue, at a concentration of 10(-5)M was found to be viricidal to herpesvirus in the light but not in the dark.

Administration, Topical

Herpetic tracheobronchitis. Cytologic and virologic detection.

Tracheobronchitis due to herpes simplex virus is a well-recognized finding in cases of burns, debilitation, or immunosuppression. Nearly all reported cases have been diagnosed at necropsy despite the possibility for clinical detection of such infections by exfoliative cytological studies, virus isolation and identification, or both. The present report details the cytologic and virologic diagnosis of herpetic tracheobronchitis in a patient with carcinoma of the lung and alcoholic fatty liver. Respiratory cells with herpetic infection cytologically showed less tendency to multinucleation than the characteristic herpes-infected cells of squamous epithelium, which may be a source of diagnostic confusion.

Aged

Histocompatibility types and viral antibodies.

Serum neutralizing (Nt) antibodies to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), and histocompatibility (HL-A) types, were determined in multiple sclerosis (MS) patients and in control subjects. Titers of Nt antibodies to HSV-1 and to HSV-2 were increased among subjects bearing HL-A3 or HL-A7 or both, whether they suffered from MS or not. The increases were statistically significant in the MS group. The MS and control groups did not differ significantly in levels of HSV-1 or HSV-2 Nt antibodies.

Antibodies, Viral

Experimental herpes simplex virus encephalitis. Effect of corticosteroids and pyrimidine nucleoside.

The effects of methylprednisolone sodium succinate and cytarabine have been examined in an experimental herpes simplex virus-induced encephalitis in rabbits. In this model herpes simplex virus (HSV) is normally cleared from the brains of untreated animals. Infected animals treated with large doses of methylprednisolone showed a slight delay in the rate of clearance of virus, and a minimal reduction in the inflammatory process, but did not otherwise differ from untreated controls. Animals treated with cytarabine displayed a notable rise in viral titers in brain at a time when virus had been cleared from untreated controls. Cytarabine-treated animals also showed persistence of intranuclear inclusions in the lesions, and moderate diminution in the extent of inflammatory response. Thus, while methylprednisolone appears to have little adverse effect on the encephalitic process, cytarabine, perhaps because of its immunosuppressive properties, results in a failure of normal clearance of virus from nervous system lesions.

Animals

Characteristic early electroencephalographic changes in herpes simplex encephalitis.

We review electroencephalograms taken from 17 patients with severe meningoencephalitis within seven days of onset of CNS symptoms and prior to cortical brain biopsies. All patients had CNS disease clinically compatible with the diagnosis of herpes simplex encephalitis (HSE). The diagnosis was demonstrated by the isolation of virus from the brain in five patients (group 1) but considered highly unlikely in the other 12 patients (group 2) by negative immunofluorescent studies and failure of viral isolation from the brain tissue. Abnormal but nonspecific EEGs with diffuse or focal slowing were found in all patients. Distinctive high-voltage, 1-cycle-per-2-to-3 seconds periodic sharp waves from unilateral temporal lobes were seen only in three of the five patients with virologically proved HSE but in none of the 12 patients without viral isolation. This EEG pattern is strikingly similar in all three patients, regardless of their age, and may be specific for the early diagnosis of HSE prior to brain biopsy. The EEGs of the other two patients with proved HSE did not contain such abnormalities. Athough periodic EEGs with some resemblance to those previously described may occur in other CNS disorders, their presence strongly suggests the diagnosis of HSE when recorded from patients with viral meningoencephalitis. Moreover, EEGs may help locate the best site for cerebral biopsy since maximal yield of the virus in this study was from unilateral temperoal lobes corresponding with the site of local EEG changes.

Adolescent

Herpes simplex virus subunit antibodies in patients with Parkinson's disease.

Serum IgG antibodies against herpes simplex virus (HSV) type 1 capsid, envelope, and excreted antigens in 52 patients with idiopathic Parkinson's disease, and in their age- and sex-matched controls, were assayed with a solid-phase radioimmunoassay. When compared with the controls, patients with Parkinson's disease were found to have a substantially increased antibody response against each of the HSV subunit antigens tested. The increased antibody response in patients with Parkinson's disease was not associated with the occurrence of recurrent HSV infections, since the difference in antibody levels was most evident when comparing patients without recurrent HSV infections with their respective control group. Consequently, the increased HSV antibody response in patient with Parkinson's disease might depend on some antigenic stimulation other than ordinary recurrent HSV infections, or alternatively, on the generally enhanced immunological reaction of the patients against HSV.

Aged

CSF viral antibodies. Evaluation in amyotrophic lateral sclerosis and late-onset postpoliomyelitis progressive muscular atrophy.

Serum and CSF from 48 patients with amyotrophic lateral sclerosis and six patients with late-onset postpoliomyelitis progressive muscular atrophy were investigated for the presence of antibody to poliovirus types 1, 2, and 3, coxsackie viruses B3 and B4, influenza A, measles, rubella, mumps, herpes simplex types 1 and 2, cytomegalovirus, varicella-zoster, and Toxoplasma gondii. These results were compared with those from 53 control patients with neuromuscular disease matched for age, sex, race, and poliovirus vaccine exposure. There was no difference either in distribution of serum or CSF antibody titers or the geometric-mean antibody titers. There was no evidence suggesting the presence of locally produced specific viral antibody within the CNS to any of the agents studied. In particular, there was no serological evidence to suggest an association between persistent infection with any poliovirus type and amyotrophic lateral sclerosis or late-onset postpoliomyelitis progressive muscular atrophy.

Adult

Nucleic acid homology studies of viral nucleic acids in idiopathic Parkinson's disease.

Reassociation kinetics analyses with radioiodinated herpes simplex type 1 DNA and influenza A/NWS RNA were performed in the presence of tissue nucleic acids from defined loci of the brains of nine patients with idiopathic Parkinson's disease, one normal control brain, and the brains of uninfected mice or mice infected with either herpes simplex type 1 virus or influenza A/NWS virus. Herpes simplex type 1 DNA was detected by an increased reassociation rate in the herpes simplex type 1 virus-infected mouse brains. Influenza A/NWS RNA was detected by reassociation in the influenza A/NWS virus-infected mouse brains. Experimental limits for the detection of homologous nucleic acids are given for each separate experiment with human or mouse tissue. Within these detection limits, nucleic acids complementary to herpes simplex type 1 DNA or influenza A/NWS RNA were not detected in any of the brains of patients with idiopathic Parkinson's disease.

Brain

Congenital herpetic keratitis.

An infant, the first-born of twins, delivered by cesarean seciton without prior rupture of the membranes, was noted to have an advanced epithellal and stromal keratitis at berth. Herpes simplex, type 1, was cultured form the cornea and from skin vesicles which developed subsequently. The advanced nature of the lesion indicates that it was acquired in utero. This appears to be the first reported case of congential herpetic keratitis.

Antibodies, Viral

Acute ocular infection by type 2 herpes simplex virus in adults.

Acute ocular infections in two adults were caused by type 2 herpes simplex virus (HSV) ("genital herpesvirus"). One patient had an acute blepharoconjunctivitis, the other an acute keratoconjunctivitis. Genital infections had preceded the eye infections, and type 2 HSV was isolated from the eyes of both patients and from the genital lesions of one patient. This strongly suggests transmission of type 2 HSV from the genital site to the eye.

Acute Disease

Herpesvirus hominis encephalitis and retinitis.

A previously healthy 44-year-old man died three weeks after the simultaneous onset of encephalitis and retinitis. Fundus changes were bilateral and included papillitis, rapidly progressive central retinal vein obstruction, and massive exudative retinal detachment. A 16-fold rise in herpesvirus hominis antibodies occured between the 10th and 20th days of illness. At autopsy, the brain showed changes characteristic of herpetic encephalitis, and cultures of the brain yielded Herpesvirus hominis type I. Intranuclear inclusion bodies typical of those produced by Herpesvirus were found by light microscopy in brain, optic nerves, retina, and choroid. Herpesvirus particles were found by electron microscopy in brain, optic nerve, and retina.

Adult

Herpes simplex virus types 1 and 2: therapeutic response to antiviral drugs.

In vitro studies have demonstrated a relative resistance of herpes simplex virus type 2 to antiviral therapy when compared with herpes simplex virus type 1. The in vivo studies, however, show an excellent therapeutic response to both antiviral drugs in experimentally induced viral keratoconjunctivitis.

Animals

Herpes simplex virus in human cornea, retrocorneal fibrous membrane, and vitreous.

A case of recurrent herpes simplex virus keratouveitis was studied using both electron microscopic and viral culture techniques. We describe a patient who had a particularly violent course, including three failed grafts, endophthalmitis, and wound leak. We report the identification of virus in a quiescent failed corneal graft and retrocorneal membrane; persistence of virus enabling its culture from the vitreous; and electron microscopic identification in the cornea removed at the third transplant. The identification of cases in which viral proliferation occurs is necessary for a greater understanding of the pathogenesis of herpetic corneal disease and for determining in which particular patient steroid therapy should be avoided.

Cornea

Herpesvirus in sensory and autonomic ganglia after eye infection.

In herpesvirus hominis (HVH) infections, virus harbored in the sensory ganglia is now thought to be the main source of recurrent infection at peripheral sites. Experimental HVH infection of the external eye in rabbits produces an acute infection and then latent infection of the trigeminal ganglion. In this study, acute infection of the automatic ganglia serving the eye (superior cervical and ciliary) as well as trigeminal ganglia occurred after HVH inoculation of rabbits' corneas with a herpes type 1 strain (RE). Latent virus infection was detected in the trigeminal ganglion of one of five animals tested six months after initial infection. Since the superior cervical and other autonomic ganglia serving the eye become infected during acute herpes simplex virus infection of the external eye in rabbits, it is possible that these ganglia are also sources of reinfection in recurrent herpetic disease of the eye. Following the initial eye disease with this virus strain, HVH shedding could not be demonstrated even after induction attempts by topically applied epinephrine or systemic use of cyclophosphamide. Thus, establishment of latent HVH infection in the ganglia and chronic shedding of virus into the external eye is not a constant feature of this animal model, but may depend on the specific strain of herpesvirus used.

Animals