Tsuyoshi Takasu

Reactivation of herpes simplex virus type 1 in patients with Bell's palsy

Reactivation of herpes simplex virus type 1 (HSV‐1) has been implicated in the pathogenesis of idiopathic peripheral facial palsy (Bells palsy). The present study used the polymerase chain reaction (PCR) to analyze the saliva of patients with Bells palsy for the presence of shed HSV‐1. The study involved 47 patients with Bells palsy, 24 patients with Ramsay Hunt syndrome, and 16 healthy HSV‐seropositive volunteers. HSV‐1 DNA was not detected in the saliva samples from HSV‐seronegative patients. The prevalence of shed HSV‐1 in patients with Bells palsy (50%) was significantly higher than that in healthy volunteers (19%, p<0.05). When saliva samples were tested within 7 days after the onset of palsy, the prevalence of shed HSV‐1 in patients with Bells palsy (40%) was significantly higher than that in patients with Ramsay Hunt syndrome (7%, p<0.05). Furthermore, HSV‐1 usually became undetectable by the second week after the onset of Bells palsy when HSV‐1 was detected during the acute phase of the disease. These findings strongly suggest that reactivation of HSV‐1 is involved in the pathogenesis Bells palsy, and indicate that PCR is a useful tool for early diagnosis of HSV‐1 reactivation in patients with Bells palsy. J. Med. Virol. 54:162–166, 1998.

Detection of Latent Herpes Simplex Virus DNA and RNA in Human Geniculate Ganglia by the Polymerase Chain Reaction

By using the polymerase chain reaction (PCR) we detected latent herpes simplex virus type 1 (HSV-1) in human geniculate and trigeminal ganglia obtained from autopsy cases. A pair of primers which were specific for a part of the HSV-1 thymidine kinase domain were used for detection of HSV DNA. We also examined the latency-associated transcript (LAT), known as latency-specific RNA, by means of reverse transcription-PCR with a pair of LAT-specific primers. HSV-1 DNA was detected in 16 of 17 (94%) trigeminal ganglia and in 15 to 17 (88%) geniculate ganglia of adults. We also demonstrated HSV-1 RNA derived from the LAT in both types of ganglia. These findings suggest that HSV-1 latently infects the majority of geniculate and trigeminal ganglia of adults, and that PCR and reverse transcription-PCR are useful tools for analysis of HSV latency.

Latent herpes simplex virus type 1 in human geniculate ganglia

SummaryViral infection, especially by reactivation of herpes simplex virus (HSV) has been considered to be a possible explanation for the pathogenesis of idiopathic peripheral facial nerve palsy (Bells palsy). We investigated whether the geniculate ganglia of man contain latent HSV type 1 (HSV-1), and compared the frequency of HSV-infected ganglia and that of latently infected neurons in human geniculate ganglia and in trigeminal ganglia. From autopsy specimens of eight adults 15 geniculate ganglia and 16 trigeminal ganglia were examined by means of in situ hybridization and immunohistochemical staining. The HSV-1 genome was detected in 11 of the 15 (71%) geniculate ganglia and in 13 of the 16 (81%) trigeminal ganglia. No HSV antigen was noted in any of the ganglia. The incidence of latently infected neurons was 0.9% in the trigeminal ganglia and 5.3% in the geniculate ganglia. The difference in percentages between the two types of ganglia was significant. Our results suggest that reactivation of latent HSV in the geniculate ganglia is a probable cause of some cases of herpetic stomatitis and of idiopathic peripheral facial nerve palsy.

Detection of varicella-zoster virus DNA in patients with acute peripheral facial palsy by the polymerase chain reaction, and its use for early diagnosis of zoster sine herpete

Varicella‐zoster virus (VZV) reactivation without cutaneous vesicles (zoster sine herpete) has been demonstrated in 8 to 25% of patients with acute peripheral facial palsy (APFP) by serological methods. To make an early diagnosis of zoster sine herpete, VZV DNA in oropharyngeal swabs from patients with APFP was examined by the polymerase chain reaction (PCR). VZV DNA was detected in oropharyngeal swabs from 6 of 36 (17%) patients with APFP by PCR. VZV DNA was detected in the oropharyngeal swabs from the six patients at their initial visit (2 to 4 days after the onset of APFP), while the anti‐VZV IgM and IgG antibody titers were not increased significantly. In contrast, VZV DNA was undetectable in the oropharyngeal swabs at the time when the VZV specific antibody response appeared. These results indicate that detection of VZV DNA in oropharyngeal swabs by PCR is more useful than currently available serological assays for the early diagnosis of zoster sine herpete in patients with APFP. J. Med. Virol. 52:316–319, 1997.

Latent Herpes Simplex Virus Type 1 in Human Vestibular Ganglia

Viral infection has been considered to be a possible pathogenesis of vestibular neuronitis, and reactivation of the herpes simplex virus (HSV) is one of the most likely causes. However, it remains unknown whether the human vestibular ganglia contain latent HSV. We examined 26 vestibular ganglia from autopsied adults in search of HSV type 1 (HSV-1). To detect HSV-1, we used polymerase chain reaction (PCR), in situ hybridization and immunohistochemical staining. HSV DNA was detected in 6 of 10 vestibular ganglia using the PCR method. However, the latency-associated transcript (LAT) of HSV-1 was negative in all of the 16 vestibular ganglia examined. No HSV antigen was detected in any of the ganglia. These results indicate that HSV-1 is latently infected in the human vestibular ganglia, and that LAT is transcribed weakly or not at all.

The Significance of Herpes Viral Latency in the Spiral Ganglia

To better understand the pathogenesis of idiopathic sudden hearing loss (ISHL), the possibility of latent virus infection in the spiral ganglion cell was considered. Only few spiral ganglion cells showed positive viral antigen after systemic guinea pig-specific cytomegalovirus (GPCMV) inoculation indicating the absence of hearing loss but the possibility of a subsequent latent infection. By using a modern molecular biological technique we have detected the herpes simplex virus type-1 (HSV-1) DNA in human spiral ganglia. The concept of establishing viral latency in the spiral ganglion cells with periods of reactivation fits with the clinical picture seen in ISHL, even though the mechanism of reactivation still remains unclear.

Distribution of herpes simplex virus types 1 and 2 genomes in human spinal ganglia studied by PCR and in situ hybridization.

Clinical data indicate that the recurring herpes simplex virus (HSV) from oro‐labial lesions is HSV subtype 1 and that the virus from genital lesions is HSV‐2. This suggests that HSV‐1 and HSV‐2 reside in latent forms in the trigeminal ganglia and sacral ganglia, respectively. However, the distribution of latent HSV‐1 and HSV‐2 infections in human spinal ganglia has not been fully examined. This report concerns the application of polymerase chain reaction (PCR) and in situ hybridization (ISH) to such a study. By using PCR and employing the respective primers, HSV‐1 and HSV‐2 DNAs were detected in 207 of 524 samples from 262 spinal ganglia (from the cervical to the sacral ganglia) examined on both sides. The percentages of HSV‐1 and HSV‐2 detected in a given set of ganglia were similar, indicating an absence of site preference. By ISH, few but positive hybridization signals were detected evenly in sacral ganglia sections. The data suggest that regional specificity of recurrent HSV infections is not due to regional distribution of latent virus, but that local host factors may be important for recurrences. J. Med. Virol. 52:136–142, 1997.

Detection of latent varicella-zoster virus infection in human vestibular and spiral ganglia

Varicella‐zoster virus (VZV) becomes latent in the sensory ganglia after primary infection and VZV DNA has been found in human trigeminal, thoracic, and geniculate ganglia. In this study, human vestibular and spiral ganglia, which do not receive innervation from the skin, were examined for VZV DNA using the polymerase chain reaction. VZV DNA was detected in 2 of 10 (20%) vestibular ganglia and in 2 of 10 (20%) spiral ganglia from five adults. VZV DNA was undetectable in either type of ganglion from a newborn and from two of the five adults. These two adults were VZV seronegative. The results indicate that VZV becomes latent in several types of sensory ganglion after primary infection and suggest the possibility that reactivation of the virus from the vestibular and spiral ganglia may cause disorders in the labyrinth. J. Med. Virol. 51:214–216, 1997.

Detection of human papillomavirus DNA in carcinomas of the nasal cavities and paranasal sinuses by polymerase chain reaction

The authors retrospectively searched for human papillomavirus (HPV) types 16 and 18 in 60 cases of carcinoma arising from the nasal cavities (NC) and paranasal sinuses (PS) by using the polymerase chain reaction (PCR) on DNA extracted from formalin‐fixed, paraffin‐embedded tissues. In cases of SCC (n = 49), the authors also compared the clinical features of patients with HPV‐positive and HPV‐negative results to determine the clinical significance of HPV. HPV 16 and 18 were detected in 7 of the 49 cases (14%) of SCC. In the other histologic types of carcinoma (n = 11), neither HPV 16 nor HPV 18 was detected. No significant differences in the clinical features were observed between patients with SCC with HPV‐positive and HPV‐negative results. The results suggest that HPV 16 and 18 are implicated in the pathogenesis of SCC arising from the NC and PS. However, the presence of HPV is not related to local progression, occurrence of metastases, or the prognosis of the patients.

Clinical significance of the epidermal growth factor receptor gene in m squamous cell carcinomas of the nasal cavities and paranasal sinuses

The authors retrospectively analyzed epidermal growth factor receptor (EGFR) gene amplification in 49 cases of squamous cell carcinoma (SCC) arising from the nasal cavities (NC) and paranasal sinuses (PS) by using slot‐blot analysis of DNA extracted from formalin‐fixed, paraffin‐embedded tissues. Also, the relationship between the results of gene analysis and the clinical features of the patients was studied to investigate the clinical significance of the EGFR in SCC of the NC and PS. Amplification of the EGFR gene was detected in 5 of the 49 cases (10%). No significant difference was observed between EGFR gene amplification and the presence of lymph node metastases, local recurrence, or prognosis. This suggests that EGFR gene amplification is not related to the local progression or metastasis of the SCC in the NC and PS. In addition, it appears that amplification of the EGFR gene is not a prognostic indicator for SCC in the NC and PS.