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Virtual-assisted lung mapping is a bronchoscopic multiple dye marking technique that facilitates sublobar lung resections for unidentifiable pulmonary tumors. Marking failure reportedly occurs in 10% of cases. To overcome this limitation, we developed indocyanine green virtual-assisted lung mapping that uses indocyanine green in addition to indigo carmine. Here, we report our initial experience of indocyanine green virtual-assisted lung mapping.

Background: Various approaches have been used to assist and facilitate segmentectomy with favorable oncological outcomes. We describe a hybrid approach comprising virtual-assisted lung mapping (VAL-MAP), which is a preoperative bronchoscopic dye-marking technique, combined with systemic indocyanine green (ICG) injection., Clinical Presentation: An asymptomatic 64-year-old man was referred to our department because of a lung nodule detected during his annual medical checkup. The chest computed-tomography image revealed a 16-mm, partly solid, ground-glass nodule in the left segment 4. Because the nodule was hardly palpable and deeply located between the left upper division segment and the left lingular segment, we performed VAL-MAP to facilitate extended left lingulectomy. Five dye markings were undertaken preoperatively. Surgery to remove the nodule was then conducted via complete three-port video-assisted thoracic surgery. The VAL-MAP markings were easily identified intraoperatively and helped locate the nodule. The intersegmental plane was identified by the ICG injection. The resection line was determined based on the intersegmental plane identified by the ICG injection and the site of the nodule suggested by the VAL-MAP markings. Following the resection line, we thoracoscopically achieved extended lingulectomy with sufficient surgical margins. The patient was discharged with no complications. The pathological diagnosis was adenocarcinoma in situ., Conclusion: The hybrid technique of VAL-MAP and systemic ICG injection can be useful for accomplishing successful extended segmentectomy.

Background: Pulmonary segmentectomy can be challenging when thoracic surgeons encounter anatomical anomalies. A displaced left apicoposterior bronchus is a rare bronchial anomaly that makes lung anatomical resection challenging. We herein present a case of successful left apicoposterior segmentectomy for lung cancer in a patient with an anomalous segmental bronchus., Case Presentation: A 70-year-old man was clinically diagnosed with early-stage lung cancer for which segmentectomy was indicated. A preoperative image revealed a displaced left apicoposterior bronchus that branched behind the left main pulmonary artery. With the aid of three-dimensional reconstruction imaging and systemic indocyanine green injection, we successfully performed left apicoposterior segmentectomy under complete video-assisted thoracic surgery. The pathological diagnosis was adenocarcinoma. The patient was alive without recurrence 8 months after segmentectomy., Conclusion: Preoperative three-dimensional imaging and systemic indocyanine green injection enabled us to successfully conduct challenging segmentectomy in a patient with an anomalous bronchus.

In intralobar pulmonary sequestrations, vascular changes similar to those in pulmonary hypertension (PH) are generally observed, such as intimal proliferation and plexiform lesions. However, to our knowledge, a sequestrated lung manifesting vascular changes with both arteritis and a plexiform lesion has never been reported. A 25-year-old man was diagnosed with intralobar pulmonary sequestration. Pathologically, both arteritis and a plexiform lesion were observed in the sequestrated lung. Systemic vasculitis syndrome was clinically excluded, and the pathological findings appeared to be associated with local PH. Arteritis is an extremely rare finding; only one case of arteritis associated with local PH has been reported in intralobar sequestration. In this case, the artery near the plexiform lesion had milder inflammation and fibrosis, suggesting that the arteritis formed prior to the plexiform lesion. This is the first case of arteritis and a plexiform lesion co-occurring in intralobar pulmonary sequestration associated with local PH. This case may shed light on the formation of plexiform lesions and their association with arteritis.

In the pursuit of minimally invasive surgery, there is no objection to the replacement of conventional open surgery with robotic surgery in highly difficult cases of pulmonary and mediastinal tumors. However, compared to video-assisted thoracoscopic surgery, the benefits of performing robotic surgery in standard lung cancer cases are few. A surgeon with master robotic skills, in addition to excellent 3-dimensional( 3D) camera control, can effectively use a retraction arm instead of increasing the number of the port. We think that such a surgeon can have an extremely high success rate. We started performing robotic surgery in September 2018 and have had more than 70 cases since then. We developed a manual to promote patient safety and common understanding between the operator and surgical assistants. In this manuscript, we introduce our current robotic surgery technique for lung cancer. The current status, problems, and the future of robotic thoracic surgery are also described.

Adenosine-to-inosine (A-to-I) microRNA editing is associated with tumor phenotypes in various cancer types. Recent analyses of The Cancer Genome Atlas (TCGA) dataset have shown several microRNAs that undergo A-to-I editing in human cancers, some of which have been reported to be associated with prognosis. Herein, we examined published small RNA deep sequencing data of 74 cases of lung adenocarcinoma (AD) and the corresponding normal counterpart (NC) specimen in silico in order to identify A-to-I microRNA editing events. Editing levels of miR-379-5p, miR-99a-5p, and miR-497-5p were lower in AD than in NC and, in a large number of cases, the editing level of miR-200b-3p was higher in AD than in NC. Difference in the editing level between AD and NC was largest for miR-99a-5p. Then, we examined the editing level of miR-99a-5p in 50 surgically resected lung adenocarcinoma cases at our institution by a conventional sequence-based method, and its association with clinical outcomes. The editing level of miR-99a-5p was significantly lower in 19 cases of AD (38%) than in corresponding NC. These cases showed a shorter overall survival as assessed using the log-rank test (P = .047). This trend was consistent with previous analyses of TCGA dataset. The altered editing level of microRNAs in lung adenocarcinoma could serve as a potential biomarker., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objectives: Women are the minority among patients with spontaneous pneumothorax, but catamenial pneumothorax (CP) is unique to them. We aimed to clarify the clinical characteristics of female patients with spontaneous pneumothorax using a nationwide database., Methods: Medical records from the Japanese Diagnosis Procedure Combination database for inpatients with pneumothorax between July 2010 and March 2016 were retrospectively reviewed. Age, underlying diseases, body mass index, smoking status, laterality, number of hospitalizations and treatments were studied., Results: We identified 157 087 patients with pneumothorax, including 27 716 (17.6%) women and 129 371 (82.4%) men. The age distribution of female patients with pneumothorax had 3 peaks: 18 years, around 40 years and 80 years; male patients had 2 peaks: 18 years and 79 years. We identified 873 patients with CP; this number was not sufficient to account for the female-specific peak around 40 years. The characteristics of female patients of reproductive age were significantly different between those with and without CP. The patients with CP were older (average age: 37.9 ± 7.7 years vs 31.3 ± 11.5 years, P < 0.001), were right side dominant (right: 64.9%, left: 6.5%), had more hospitalizations (average number of hospitalizations: 1.6 ± 0.9 vs 1.3 ± 0.6, P < 0.001) and had more frequently undergone surgery (57.1% vs 37.3%, P < 0.001)., Conclusions: The age distribution of women with pneumothorax had 3 distinct peaks while that of men had 2. CP has different characteristics from other types of pneumothorax, thus requiring different treatment strategies for women of reproductive age.

Background and Purpose- Endovascular therapy is effective against acute cerebral large vessel occlusion (LVO). However, many patients do not receive such interventions because of the lack of timely identification of the type of stroke. If the types of stroke (any stroke, LVO, intracranial hemorrhage [ICH], and subarachnoid hemorrhage [SAH]) were to be predicted at the prehospital stage, better access to appropriate interventions would be possible. Japan Urgent Stroke Triage (JUST) score was clinical prediction rule to classify suspected patients of acute stroke into different types at the prehospital stage. Methods- We obtained information for signs and symptoms and medical history of consecutive suspected patients of acute stroke at prehospital stage from paramedics and final diagnosis from the receiving hospital. We constructed derivation cohort in the historical multicenter cohort study from June 2015 to March 2016 and validation cohort in the prospective multicenter cohort study from August 2016 to July 2017. The derivation and the validation cohorts included 1229 and 1007 patients, respectively. We constructed multivariate logistic regression models with 21 variables to develop clinical prediction rules, which distinguish between different types of stroke: any stroke, LVO, ICH, and SAH. Results- Among the 1229 patients (median age, 72 years; 55% men) in the derivation cohort, 533 stroke, 104 LVO, 169 ICH, and 57 SAH cases were observed. The developed rules showed that the areas under the receiver operating curves were 0.88 for any stroke, 0.92 for LVO, 0.84 for ICH, and 0.89 for SAH. The validation cohort of 1007 patients (median age, 75 years; 56% men) showed that the areas under the curves of any stroke, LVO, ICH, and SAH were 0.80, 0.85, 0.77, and 0.94, respectively. Conclusions- These clinical prediction rules can help paramedics classify the suspected patients of stroke into any stroke, LVO, ICH, and SAH groups with excellent accuracy.

Background: Cisplatin is a key drug for treating lung adenocarcinoma, and its sensitivity to cisplatin is directly related to prognosis. We aimed to reveal the roles of genes related to glutathione synthesis (glutamate-cysteine ligase catalytic subunit, GCLC) and cystine uptake (cystine/glutamate transporter, xCT and CD44v8-10) in cisplatin resistance and prognosis in lung adenocarcinoma., Methods: We established cell lines stably expressing GCLC, xCT, standard isoform of CD44, and CD44v8-10, and investigated their sensitivities to cisplatin. We also measured mRNA expression levels of these genes in the tumor tissues from 92 lung adenocarcinoma patients. Patients were divided into high-expression (upper quartile, N = 23) and low-expression groups (remaining patients, N = 69). Recurrence-free survival, overall survival (N = 92), and post-recurrence survival (N = 22) were selected as endpoints., Results: Compared with the control green fluorescent protein-expressing cell line (inhibitory concentration 50:6.9 μM), all the stable cell lines were more resistant to cisplatin (12.9 μM, P = 0.025; 13.9 μM, P = 0.028; 26.7 μM, P = 0.001; 17.7 μM, P = 0.008, respectively). In contrast, there was no significant difference in recurrence-free or overall survival between the high- and low-expression groups for any of the genes. However, high expression of GCLC was a risk factor for poorer post-recurrence survival (hazard ratio, 6.26; 95% confidence interval, 1.37-28.7; P = 0.018)., Conclusion: High expression levels of genes related to glutathione synthesis and cystine uptake promote cisplatin resistance in lung adenocarcinoma cell lines. High expression of GCLC in tumor tissue may be a potential predictor of treatment failure.

An asymptomatic 26-year-old man received an annual medical check-up, and chest X-ray showed a protrusion of the aortopulmonary window. Chest computed tomography (CT) revealed an anterior mediastinal tumor and cysts with thin wall and septum enhancement. The preoperative diagnosis was cystic thymoma or malignant lymphoma. We performed total resection of the tumor through a median sternotomy. The pathological findings revealed seminoma, positive for c-kit stain, and multilocular thymic cysts. Cysts were lined by normal squamous epithelium and no seminoma cells were located on their surface. So, cysts were probably secondary changes caused by seminoma cells themselves or inflammatory stimulations. No invasion to adjacent structures was seen. After the surgery, testicular ultrasound imaging and abdominal, pelvic, and cerebral CT showed no apparent tumor or enlarged lymph nodes; however, an abnormal uptake in the right mesenteric lymph node was pointed out by 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan. The patient received four courses of bleomycin, etoposide, and cisplatin (BEP) as adjuvant chemotherapy. Follow-up PET scan revealed no uptake in the right mesenteric lymph node. To date, no recurrence or metastasis has been identified for 16 months.

Objective: Recent reports have shown that endoplasmic reticulum stress is associated with cancer. However, the impacts of endoplasmic reticulum stress on the prognosis of lung cancer are unknown. Therefore, in this study, we sought to reveal the relationship between the expression of endoplasmic reticulum stress-related genes (endoplasmic reticulum oxidoreductase 1L, protein kinase RNA-like endoplasmic reticulum kinase, activating transcription factor 6 and inositol-requiring kinase 1) and the outcome of lung adenocarcinoma., Methods: One hundred and twenty-six patients with surgically resected lung adenocarcinomas were subjected to an endoplasmic reticulum stress-related mRNA expression analysis using quantitative RT-PCR. The following parameters were analyzed for all the study patients: age, sex, disease stage, smoking status, lymph node invasion (ly), vascular invasion (v) and EGFR mutation status. We assigned patients to either a high-expression group or a low-expression group according to the expression levels of endoplasmic reticulum stress-related genes., Results: High expressions of endoplasmic reticulum stress-related genes were observed in patients with lower stages of lung adenocarcinoma and minimal vascular invasion. A Kaplan-Meier analysis showed significant differences in recurrence-free survival and overall survival between high-expression group and low-expression group. High inositol-requiring kinase 1 expression was an independent predictor of recurrence-free survival among patients with lung adenocarcinoma (hazard ratio, 0.396; 95% confidence interval, 0.188-0.834; P = 0.015)., Conclusions: Inositol-requiring kinase 1 may be a useful biomarker to predict recurrence in surgically resected lung adenocarcinoma patients., (© The Author 2017. Published by Oxford University Press.)

This study analyzed the efficacy and safety of the "drip, ship, and retrieve (DSR)" approach used to improve patient access to thrombectomy for acute stroke., Methods: The study participants were 45 patients who underwent thrombectomy following intravenous tissue plasminogen activator between September 2013 and August 2015. Patients were divided into two groups according to whether they were transferred from another hospital (DSR group; n = 33) or were brought in directly (Direct group; n = 12). The two groups were compared based on their baseline characteristics, time from stroke onset to reperfusion, outcome, and adverse events., Results: There were no significant differences in baseline characteristics. Time from onset until admission to our facility was significantly shorter in the Direct group (56.9 min) than in the DSR group (163.5 min) (P <0.0001). Conversely, time from arrival at the hospital to arterial puncture was significantly shorter in the DSR group (25.0 min) than in the Direct group (109.5 min) (P <0.0001). Time from onset to reperfusion did not differ significantly between the groups. There was no significant difference in patient outcomes, with a modified Rankin scale score of 0-2 (44.8% in DSR group versus 48.7% in Direct group). Moreover, there was no difference in the incidence of adverse events., Discussion: Despite the time required to transfer patients in the DSR group between hospitals, reducing the time from arrival until commencement of endovascular therapy meant that the time from onset to reperfusion was approximately equivalent to that of the Direct group., Conclusion: Time-saving measures need to be taken by both the transferring and receiving hospitals in DSR paradigm., Competing Interests: N. Hiyama, M. Shirakawa, K. Uchida, Y. Oki, S. Shindo, and K. Tokuda have no conflicts of interest. S. Yoshimura received a research grant from Takeda Pharmaceutical Co., and Terumo, Speakers’ Bureau/Honoraria from Bayer, Otsuka Pharmaceutical Co., Nippon Boehringer Ingelheim Co. Ltd. NH, SY, MS, KU, YO, and KT have registered online Self-reported COI Disclosure Statement Forms through the website for JNS members.

Introduction: Two strategies for selecting neoantigens as targets for non-small cell lung cancer vaccines were compared: (1) an "off-the-shelf" approach starting with shared mutations extracted from global databases and (2) a personalized pipeline using whole-exome sequencing data on each patient's tumor., Methods: The Catalogue of Somatic Mutations in Cancer database was used to create a list of shared missense mutations occurring in more than 1% of patients. These mutations were then assessed for predicted binding affinity to HLA alleles of 15 lung cancer patients, and potential neoantigens (pNeoAgs) for each patient were selected on this basis. In the personalized approach, pNeoAgs were selected from missense mutations detected by whole-exome sequencing of the patient's own samples., Results: The list of shared mutations included 22 missense mutations for adenocarcinoma and 18 for squamous cell carcinoma (SCC), resulting in a median of 10 off-the-shelf pNeoAgs for each adenocarcinoma (range 5-13) and 9 (range 5-12) for each SCC. In contrast, a median of 59 missense mutations were identified by whole-exome sequencing (range 33-899) in adenocarcinoma and 164.5 (range 26-232) in SCC. This resulted in a median of 46 pNeoAgs (range 13-659) for adenocarcinoma and 95.5 (range 10-145) for SCC in the personalized set. We found that only one or two off-the-shelf pNeoAgs were included in the set of personalized pNeoAgs-and then in only three patients, with no overlap seen in the remaining 12 patients., Conclusions: Use of an off-the-shelf pipeline is feasible but may not be satisfactory for most patients with non-small cell lung cancer. We recommend identifying personal mutations by comprehensive genome sequencing for developing neoantigen-targeted cancer immunotherapies., (Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

A 63-year-old male patient was referred to our department for an abnormal shadow in the left middle lung field. The patient underwent trans bronchial lung biopsy and pathological finding was adenocarcinoma. Computed tomography( CT) showed mass in the left lower lobe, nodules in the bilateral adrenal glands, liver, pancreas and lumbar bone. When he was admitted to our hospital for chemotherapy, chest X-ray showed left pneumothorax and a chest tube was placed. Several days later, he complained of sudden abdominal pain and abdominal CT revealed free air around small intestine. Emergency operation was done and the perforation of the small intestine due to metastasis was found. He underwent partial resection of small intestine and left lower lobectomy. Pathological diagnosis was pulmonary pleomorphic carcinoma and small intestine metastasis.

Mixed squamous cell and glandular papilloma (mixed papilloma) of the lung is an extremely rare neoplasm, with only 10 cases reported so far in the English literature. We present a case study of endobronchial mixed papilloma with immunohistochemical and etiological investigations. A 49-year-old male with a smoking history complained of hemoptysis, presented with a lung mass closely adjacent to large vessels in the computed tomography findings, and underwent lobectomy. The 3.0-cm sized polypoid tumor was histologically diagnosed as endobronchial mixed papilloma. Immunohistochemically, intracellular mucin was positive for MUC5AC, which is expressed in tracheobronchial goblet cells. CAM5.2 and CK19 were diffusely positive, indicating that the tumor originated from the columnar epithelium by squamous metaplasia. CEA and CA19-9 were focally positive. A human papillomavirus (HPV) investigation with in situ hybridization using a wide spectrum probe and a newly-developed PCR system did not detect any HPV infection. Including this case with a detailed HPV investigation, all of the reported cases of mixed papilloma were HPV-negative, and a literature review including newly-reported cases indicated a high frequency of smoking in such cases. Endobronchial mixed papillomas might have a smoking-related etiology., (© 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.)

In order to clarify relationships among genetic diversity, virulence, and other characteristics of conidia, 46 isolates of Verticillium lecanii from various hosts and geographical locations were examined. The internal transcribed spacer (ITS) and intergenic spacer (IGS) regions of ribosomal DNA (rDNA), mitochondrial small subunit rDNA (mt-SrDNA) and beta-tubulin were analyzed by PCR-RFLP. PCR-single stranded conformational polymorphism (SSCP) was performed on regions of the mitochondrial large subunit rDNA, mt-SrDNA, beta-tubulin and histone 4. There were no relationships among the results of RFLP, SSCP, isolation source, and location. However, amplified product size of IGS did have relationships with conidia size and sporulation. Six isolates with 4.0-kb IGS products had large conidia dimensions, and yielded low numbers of conidia compared with other isolates. Three out of the six isolates were high virulence (over 90%) against green peach aphids. Furthermore, double-stranded RNA (dsRNA) was detected in 22 out of 35 V. lecanii isolates and related with the amplicon sizes of IGS, though not with virulence or isolation location. Isolates containing dsRNA were divided into six distinct types based on banding pattern. These data demonstrate the level of genetic diversity of V. lecanii, and suggest relations among the genetic properties and conidial morphology.

Conditions necessary for the precise measurement of free L-fucose in urine by an enzymic method using L-fucose dehydrogenase have been studied. The normal urinary levels of L-fucose were 16.4 /+- 9.1 micrograms/ml in children (22.2 /+- 6.5 micrograms/mg of creatinine) and 17.7 /+- 8.5 micrograms/ml in adults (16.6 /+- 5.7 micrograms/mg of creatinine). There was a close correlation between the concentration of free L-fucose and that of creatinine. A close correlation was also found between the concentration of free L-fucose and alpha-L-fucosidase activity. Thus, it was suggested that the free L-fucose in urine reflected the metabolism of L-fucose or L-fucose-containing glycoconjugates. In a preliminary screening test, several urine samples which showed high concentrations of free L-fucose, namely cases of "fucosuria" were found.

We applied the direct immunoperoxidase method to estimate the susceptibility to IDU of 17 strains of the virus which were isolated from the patients with active epithelial lesions of herpetic keratitis. All the strains were found to be sensitive below the IDU concentration of 5 micrograms/ml. The findings obtained by this method were in good agreement with those by the fluorescent antibody technique. The present method is specific and simple. It offers clear-cut interpretation and a permanent record of the results.

Changes in viral morphology and localization of viral antigens induced by 5-iodo-2'-deoxyuridine (IDU) were studied using herpes simplex virus-infected monolayers of cultured rabbit corneal cells. A direct antibody enzyme method was employed for immunoelectron and light microscopy. There was no significant difference between the control and the IDU groups in the intracellular distribution of antigen up to 2 hours after infection. At 2 hours after infection, intracytoplasmic antigen began to appear in control and IDU-treated cells either in patchy distributions or in association with rough endoplasmic reticulum. Intranuclear staining appeared also at 2 hours after infection as a diffuse fine granular reaction. At 3 hours after infection, the intracytoplasmic reaction became more or less diffuse and there was slightly more cytoplasmic staining in the untreated group. At 6 hours after infection, reaction products increased in the cytoplasm and the nuclei in both groups but IDU-treated cells showed less intracytoplasmic and more intranuclear staining. The nuclear envelope was stained positive in both groups but IDU-treated cells showed a decreased reaction in the cytoplasmic membranous structure and fewer reaction deposits on the cell surface. At 12 and 18 hours after infection, the intranuclear accumulation of reaction products after IDU treatment became more evident. Progeny virus particles were significantly fewer in the presence of IDU: Nucleocapsids were found but in a greatly reduced number and only one incompletely enveloped particle was found. The morphology of the individual nucleocapsid, however, was not significantly altered by treatment with IDU. The preponderance of reaction substances in the nuclei compared to the cytoplasm in treatment groups may reflect distorted protein synthesis and may provide morphological evidence of the biochemical hypothesis of IDU efficacy: IDU exerts its antiviral effects through abnormal protein synthesis and the resultant defects in capsid assembly. Decreased reaction substances in the membranous structures of the cytoplasm may be related to reduced or abnormal production of envelope-associated viral antigens.

L-Fucose dehydrogenase [EC 1.1.1.122] was isolated from a rabbit liver extract and purified about 390-fold with a yield of approximately 13%. The purification procedures included treatment with protamine, ammonium sulfate fractionation, treatment with acid, DE-32 celluose colum chromatography, gel filtration on Sephadex G-100, preparative polyacrylamide gel electrophoresis, and affinity chromatography on 5' AMP-Sepharose 4B. The last procedure, affinity chromatography on 5' AMP-Sephadex 4B, was useful for the removal of other dehydrogenases. The eznyme which was homogeneous, as shown by polyacrylamide gel electrophoresis, had a molecular weight of about 92,000. The optimum pH was at 10.0 and isoelectric point at 5.2. The enzyme accepted both L-fucose and D-arabinose as substrate, but was specific for NAD+ as coenzyme. Km values were 0.15 mM, 1.4 mM, and 0.7 mM for L-fucose, D-arabinose, and NAD+, respectively. A single enzyme catalyzed the oxidation of L-fucose and D-arabinose, which had the same configurations of hydroxyl groups from C-2 to C-4. The reaction products obtained with L-fucose as substrate were L-fucono-lactone and L-fuconic acid. The L-fucono-lactone was an immediate product of oxidation and was hydrolyzed to L-fuconic acid spontaneously. This reaction was irreversible. Therefore, it is likely that L-fucose dehydrogenase is involved in the initial step of the catabolic pathway of L-fucose in rabbit liver.

C3H/He and BALB/c mice were inoculated with herpes simplex virus (HSV) by corneal or intraperitoneal route. The mouse splenocytes were analyzed to determine the level and mode of cytotoxic T lymphocyte (CTL) induction by a cytotoxicity test, using HSV-infected L929 cells and 3T3 cells as the target cells. To enhance the activities of CTL, mouse splenocytes were restimulated by lipopolysaccharide-induced lymphoblasts (LPS-blasts) infected with HSV before assay. HSV infection by both corneal and intraperitoneal routes induced H-2 restricted T lymphocyte responses specific for HSV. This CTL response became detectable on day 6 in mice with herpetic keratitis and on day 4 with intraperitoneal infection, but 10 days after infection the CTL activities of both groups reached the same level. A high response level persisted as long as 28 days. These results suggest that the protective mechanism in herpetic keratitis is similar to the mechanism in intraperitoneal infection.