Search

Immune tolerance is established in the eye to prevent permanent blindness associated with destructive damage to the cornea and retina caused by immune cell infiltration; hence, the immune responses and subsequent inflammations are strongly suppressed. While non-infectious uveitis develops from a disruption of immune tolerance in the eye, its onset is a result of accumulating etiologic factors, including genetic predisposition, environmental factors, and aging. Many non-infectious uveitis cases are genetically predisposed to human leukocyte antigen (HLA) as the most substantial disease susceptibility region. HLA class I molecules are critical for natural killer (NK) cells to distinguish between self and non-self. The killer cell Ig-like receptor (KIR) family is one of the essential components of these receptors. Evidence has accumulated that NK cells are involved in innate and acquired immunity by interacting with other immunocompetent cells to develop several autoimmune diseases. This review summarizes the possible role of KIR in the development of non-infectious uveitis.

Jutaro Nakamura,1,2 Tomoyuki Kamao,1 Arisa Mitani,1 Nobuhisa Mizuki,2 Atsushi Shiraishi1 1Department of Ophthalmology, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan; 2Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, JapanCorrespondence: Jutaro Nakamura, Department of Ophthalmology, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan, Tel +8189-960-5361, Fax +8189-960-5364, Email jutaro_n@yokohama-cu.ac.jpPurpose: This study aimed to evaluate the accuracy of the lacrimal syringing test (syringing) in relation to dacryocystography (DCG) and dacryoendoscopy (DE) in lacrimal pathway (LP) obstruction.Methods: We retrospectively reviewed 101 patients (188 LPs) who underwent syringing, cone-beam computed tomography (CBCT)-DCG, and DE to diagnose the degree and site of LP obstruction. The degree of obstruction was classified into patent, partial obstruction, and complete obstruction. The degree of LP obstruction was determined by combining the findings of DE and CBCT-DCG and was designated as DCG+DE. When differentiating complete or partial obstruction on DE was uncertain, complete or partial obstruction was assigned if the DCG showed evidence of contrast media obstruction or passage, respectively. The consistency between syringing and DCG+DE was evaluated by calculating the weighted kappa coefficient.Results: The sensitivity and specificity of syringing were 94% and 89%, respectively. The weighted Cohen’s kappa value of agreement between syringing and DCG+DE was κ = 0.73 (SE = 0.04, 95% confidence interval [CI]: 0.66– 0.80, p < 0.01). When divided into presaccal and postsaccal obstruction categories, the kappa values were κ = 0.40 (SE = 0.11, 95% CI: 0.19– 0.62, p < 0.01) and 0.55 (SE = 0.09, 95% CI: 0.37– 0.73, p < 0.01), respectively. Furthermore, when limited to common canaliculus obstruction (stenoses), which accounted for 78% (46 LPs) of the total presaccal obstructions, the kappa value was κ = 0.29 (SE = 0.12, 95% CI: 0.05– 0.54, p = 0.021), which demonstrated the lowest consistency between syringing and DCG+DE.Conclusion: Syringing was “substantially” in agreement with DCG+DE in detecting the degree of LP obstruction. Moreover, syringing was a sufficiently sensitive and specific test when performed by an experienced clinician. However, distinguishing between complete and partial obstructions by syringing was sometimes difficult, particularly in the common canaliculus obstruction (stenosis).Keywords: epiphora, nasolacrimal duct, lacrimal passage obstruction, stenosis, lacrimal drainage system, lacrimal sac, lacrimal syringing, irrigation, dacryocystography, dacryoendoscopy, weighted kappa coefficient

Aim To investigate the consistency of diagnostic findings in lacrimal syringing, dacryocystography (DCG), and dacryoendoscopy in the obstruction of the lacrimal drainage system (LDS). Methods We retrospectively examined 113 patients (211 LDS) who underwent syringing, DCG, and dacryoendoscopy to evaluate LDS obstruction. LDS obstruction was compared by classifying grade and site into three levels, respectively. The diagnostic consistency between the examinations was assessed by determining the weighted kappa value. Results A total of 25 male (49 LDS) and 88 female patients (162 LDS) were included in this study. Obstructions were observed in 77.4%, 60.0%, and 81.3% of LDS by syringing, DCG, and dacryoendoscopy, respectively. Regarding the agreement in obstruction grade, Cohen’s kappa value for DCG and dacryoendoscopy was 0.65 (95% confidence interval [CI]: 0.56–0.74). Although DCG diagnosed as patent in 38.4% of all LDS, 47.9% of them revealed partial or complete obstruction by dacryoendoscopy. Meanwhile, DCG and dacryoendoscopy showed consistency in the obstruction site in 77.9% of LDS. When discrepancies were observed between syringing and dacryoendoscopy in detecting the obstruction site, the combined diagnosis of syringing and DCG reached dacryoendoscopy findings at the 99% level. Conclusions “Substantial” agreements were found among the three examinations in diagnosing obstruction grade and site (Fleiss κ > 0.6 for both). Then, the highest agreement was observed between syringing and dacryoendoscopy in determining the obstruction site (κ = 0.7). The lowest agreements were observed between syringing and DCG in diagnosing the obstruction grade and site (κ = 0.55 for both).

Purpose: To retrospectively investigate the agreement of diagnostic findings in syringing, dacryocystography (DCG), and dacryoendoscopy in the obstruction of the lacrimal drainage system (LDS).Design: Retrospective, analytical observational studyMethods: We examined 113 patients (211 LDS) who underwent syringing, DCG, and dacryoendoscopy to preoperatively evaluate LDS obstruction. Obstruction was compared by classifying the obstruction grade and site into three levels, respectively. The diagnostic agreement between tests was assessed by determining the weighted kappa value.Results: A total of 25 male (49 LDS) and 88 female patients (162 LDS) were included in this study. Obstruction was observed in 77.4%, 60.0%, and 81.3% of LDS by syringing, DCG, and dacryoendoscopy, respectively. Regarding the agreement in obstruction grade, Cohen’s kappa value for DCG and dacryoendoscopy was 0.65 (95% confidence interval [CI]: 0.56–0.74). DCG found no obstruction in 38.4% of all LDS, whereas 47.9% of them showed stenosis or obstruction by dacryoendoscopy. Meanwhile, DCG and dacryoendoscopy showed consistency in the obstruction site in 77.9% of LDS. When discrepancies were observed between syringing and dacryoendoscopy to detect the obstruction site, the combination of syringing and DCG reached dacryoendoscopy findings at the 99% level.Conclusions: “Substantial” agreements were found in the diagnostic findings among the three examinations. Then, the highest agreement was observed between syringing and dacryoendoscopy in determining the obstruction site. The lowest agreements were observed between syringing and DCG in diagnosing the obstruction grade and site.

Purpose: We retrospectively investigated the agreement of the diagnostic findings of syringing, dacryocystography (DCG), and dacryoendoscopy in the obstruction of the lacrimal drainage system (LDS). Methods: We examined 113 patients (211 LDS) who underwent syringing, DCG, and dacryoendoscopy for preoperative evaluation of LDS obstruction. Obstruction was compared by classifying the grade and the site of obstruction into three levels, respectively. The diagnostic agreement between the tests was assessed by determining the weighted Kappa value. Results: 25 male (49 LDS) and 88 female patients (162 LDS) were included in this study. LDS obstruction was observed in 77.4% of the cases by syringing, 60.0% by DCG, and 81.3% by dacryoendoscopy. Regarding the agreement in the obstruction grade, Cohen's Kappa value for DCG and dacryoendoscopy was 0.65 (95%CI: 0.56–0.74). Meanwhile, the DCG and dacryoendoscopy showed consistency in the site of obstruction in 77.9% of the cases. DCG found no obstruction in 38.4% of all cases, whereas 47.9% of them showed stenosis or obstruction by dacryoendoscopy. When discrepancies were observed between syringing and dacryoendoscopy to detect the site of obstruction, the combination of syringing and DCG reached the dacryoendoscopy findings at the 99% level. Conclusions: "Substantial" agreements were found between the diagnostic findings of the three examinations. Among them, the highest agreement was between syringing and dacryoendoscopy in determining the site of obstruction. The lowest agreements were between syringing and DCG in diagnosing the grade and the site of obstruction.

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.

Pseudomonas aeruginosa (P. aeruginosa) infection is one of the major causes of keratitis. However, effective prophylactic and therapeutic vaccines against P. aeruginosa keratitis have yet to be developed. In this study, we explored the use of P. aeruginosa membrane vesicles (MVs) as a prophylactic vaccine as well as the use of immune sera derived from P. aeruginosa MV-immunized animals as a treatment for P. aeruginosa corneal infections in C57BL/6 mice., C57BL/6 mice were intramuscularly immunized with P. aeruginosa MVs; the mouse corneas were then scarified and topically infected with several P. aeruginosa strains, followed by determination of corneal clinical score and corneal bacterial load. Next, immune sera derived from P. aeruginosa MV-immunized ICR mice were administered intraperitoneally to naïve C57BL/6 mice, followed by topical P. aeruginosa challenge. Finally, the immune sera were also used as a topical treatment in the mice with established P. aeruginosa corneal infections., P. aeruginosa-specific IgG and IgA antibodies induced by intramuscular immunization were detected not only in the sera but also in the eye-wash solution. Both active and passive immunization significantly inhibited P. aeruginosa corneal infection. Finally, topical treatment with immune sera in the mice with established P. aeruginosa corneal infections notably decreased the corneal clinical score and corneal bacterial load., P. aeruginosa keratitis can be attenuated by vaccination of P. aeruginosa MVs and topical application of P. aeruginosa MV-specific immune sera.

Jutaro Nakamura,1,2 Tomoyuki Kamao,1 Arisa Mitani,1 Nobuhisa Mizuki,2 Atsushi Shiraishi1 1Department of Ophthalmology, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan; 2Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, JapanCorrespondence: Jutaro Nakamura, Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan, Tel +81-89-960-5361, Fax +81-89-960-5364, Email nakamura.jutaro.lt@ehime-u.ac.jpPurpose: The dacryoendoscope is a practical instrument for the examination and the treatment of lacrimal duct obstruction. Nevertheless, as it is a rigid fiberscope, manipulation of the endoscope is somewhat affected by the patient’s lacrimal duct alignment and the skeletal structure of the face. The morphology and inclination of the lacrimal duct vary among individuals and ethnic groups. We aimed to evaluate the alignment of the lacrimal duct from the perspective of endoscopic maneuverability in a Japanese population.Methods: This retrospective study analyzed the cone-beam computed tomography dacryocystography (CBCT-DCG) images of 102 patients diagnosed with unilateral primary acquired nasolacrimal duct obstruction (PANDO) at Ehime University Hospital from December 2015 to May 2021. The following parameters of the lacrimal duct on the contralateral side of unilateral PANDO were investigated: (1) angle formed by the superior orbital rim–internal common punctum–nasolacrimal duct opening, (2) angle formed by the lacrimal sac and the nasolacrimal duct, (3) length of the lacrimal sac, and (4) length of the nasolacrimal duct.Results: Measurements of the above parameters were (1) 10.2° ± 7.8° (range, − 11° to +27°), (2) − 6.3° ± 14.1° (range, − 43° to +40°), (3) 8.9 ± 2.3 mm (range, 4.3– 17.1), and (4) 13.2 ± 2.7 mm (range, 5.7– 20.7), respectively. The Shapiro–Wilk test demonstrated that the values of all parameters, except (3), followed a normal distribution (p = 0.55, 0.30, 0.0002, and 0.39, respectively). No significant difference was found between the female and male groups (p > 0.05).Conclusion: This study reported anthropometric analysis data of the morphology of the lacrimal ducts using CBCT-DCG in a Japanese population. In our cohort, the line from the superior orbital rim through the internal common punctum to the nasolacrimal duct opening inclined anteriorly in 92% of the patients.Keywords: dacryocystography, cone-beam computed tomography, dacryoendoscope, primary acquired nasolacrimal duct obstruction, endoscopic-assisted nasolacrimal duct intubation

Purpose: The dacryoendoscope is a practical instrument for the examination and the treatment of lacrimal duct obstruction. Nevertheless, being a rigid fiberscope, manipulation of the endoscope is somewhat affected by the patient's lacrimal duct alignment and the skeletal structure of the face. The morphology and inclination of the lacrimal duct differ among individuals and ethnic groups. We aimed to evaluate the alignment of the lacrimal duct from the perspective of endoscopic maneuverability in a Japanese population.Methods: We retrospectively analyzed the CBCT-DCG images of 102 cases diagnosed with unilateral primary acquired nasolacrimal duct obstruction (PANDO) at Ehime University Hospital from December 2015 to May 2021. We investigated the following parameters of the lacrimal duct on the contralateral side of unilateral PANDO: 1) the angle formed by the superior orbital rim–internal common punctum–nasolacrimal duct opening, 2) the angle formed by the lacrimal sac and the nasolacrimal duct, 3) the length of the lacrimal sac, 4) the length of the nasolacrimal duct.Results: The measurement results were as follows: 1) 10.2 ± 7.8° (range, −11° to +27°); 2) −6.3 ± 14.1° (range, −43° to +40°); 3) 8.9 ± 2.3 mm (range, 4.3–17.1); 4) 13.2 ± 2.7 mm (range, 5.7–20.7). Of these parameters, values of all except 3) followed a normal distribution.Conclusions: We reported anthropometric data analyzing the morphology of the lacrimal ducts using CBCT-DCG in a Japanese population. In our cohort, the line from the superior orbital rim through the internal common punctum to the nasolacrimal duct inclined anteriorly in 92% of cases. In such cases, a probe with a bent or curved tip was considered more appropriate than a straight-type probe.

Purpose: We compared the difference in postoperative patency rates due to the differences in the diameter of silicone tubes used for bicanalicular intubation for the treatment of nasolacrimal duct obstruction (NLDO). Methods: Patients diagnosed with NLDO at Ehime University Hospital between August 2013 and November 2020 who underwent endoscopic-assisted nasolacrimal duct intubation (ENDI) were included in the study. The patients involved were 130 cases and 157 sides (age 72.6 ± 11.3 years) who were eligible for follow-up for more than six months after the removal of the lacrimal silicone tube. The postoperative recurrence rate was compared retrospectively based on the difference in tube caliber. The patients were divided into two groups: those intubated with a 1.5-mm large diameter tube (Group LD) and those with a 1.0-mm normal diameter tube (Group ND). The survival rates of the two groups at one year after tube removal were compared by Kaplan-Meier's curve and Restricted mean survival time (RMST) method with τ = 365 days. Results: There were no significant differences in age, gender, or observation period after tube removal between the two groups. Meanwhile, the preoperative occlusion period was significantly longer in the ND group. The recurrence rate after tube removal was significantly lower in the LD group (12 / 85 sides, 14.1%) compared to the ND group (27 / 72 sides, 37.5%) (p = 0.001). The patency rate at one year after removal of the lacrimal tube was 0.857 (0.754-0.919) in the LD group and 0.739 (0.617-0.828) in the ND group. In comparing patency rates by the RMST method at τ = 365 days, the RMST difference, RMST ratio, and RMTL ratio were significantly higher in the LD group at p = 0.045, 0.052, and 0.046, respectively. Conclusion: Regarding the bicanalicular silicone tube intubation, the patency rate at one year after removal was significantly higher in the thicker tubes with a diameter of 1.5 mm compared with that of a diameter of 1.0 mm for the treatment of NLDO.

The strongest genetic risk factor of Behçet’s disease (BD) is HLA-B*51. Our group previously reported that HLA-A*26 is independently associated with the risk of the onset of BD apart from HLA-B*51. Here, we re-evaluated the association between HLA-A*26 and BD in the Japanese population. We also performed a comprehensive literature search and meta-analyzed the extracted published data concerning the relationship between HLA-A*26 and BD to estimate the odds ratio (OR) of HLA-A*26 to BD. In this study, we genotyped 611 Japanese BD patients and 2,955 unrelated ethnically matched healthy controls. Genotyping results showed that the phenotype frequency of HLA-A*26 was higher in BD patients than in controls (OR = 2.12, 95% CI: 1.75–2.56). Furthermore, within the HLA-B*51-negative populations, the phenotype frequency of HLA-A*26 was significantly higher in BD patients than in controls (OR = 3.10, 95% CI: 2.43–3.95). Results obtained from meta-analysis combined with our data showed that the modified OR of HLA-A*26 became 1.80 (95% CI:1.58–2.06), whereas within the HLA-B*51-negative population, the modified OR became 4.02 (95% CI: 2.29–7.05). A subgroup analysis arranged by the geographical regions showed HLA-A*26 is in fact associated with the onset of BD in Northeast Asia (OR = 2.11, 95% CI: 1.75–2.56), but not in the Middle East or in Europe.

We discuss the use of pluripotent stem cell lines carrying fluorescent reporters driven by retinal promoters to derive three-dimensional (3-D) retina in culture and how this system can be exploited for elucidating human retinal biology, creating disease models in a dish, and designing targeted drug screens for retinal and macular degeneration. Furthermore, we realize that stem cell investigations are labor-intensive and require extensive resources. To expedite scientific discovery by sharing of resources and to avoid duplication of efforts, we propose the formation of a Retinal Stem Cell Consortium. In the field of vision, such collaborative approaches have been enormously successful in elucidating genetic susceptibility associated with age-related macular degeneration.

We aimed to develop a new treatment against antibi- otic-resistant bacteria by focusing on cytoplasm of Kumazasa bamboo leaf. The cytoplasmic extract displ ays potent bactericidal action against Gram-positive ba cte- ria such as Staphylococcus aureus, Enterococci and Strep- tococcus pneumoniae and also multi-antibiotic resis tant MRSA (methicillin-resistant Staphylococcus aureus) and VRE (vancomycin-resistant Enterococci) strains. It in- duced bacteriolysis by firmly aggregating MSSA (me- thicillin-susceptible Staphylococcus aureus) and MR SA, and by lysis of VSE (vancomycin-susceptible Entero- cocci) and VRE. Clinical isolates of MRSA (30 strai ns in total) were susceptible to this extract, which g ave MICs of Kumazasa-cytoplasmic extract ranging from 1.6 to 6.3%. The antibacterial action was bactericidal on scan- ning electron microscopy (SEM) analysis. A synergis tic effect of this extract with ampicillin (ABPC) was obvi- ously observed in all MRSA strains. The synergistic ef- fect with vancomycin (VCM) was observed against VRE . The combination with clarithromycin (CAM) or tetrac y- cline (TC) additively enhanced the antibacterial ac tivity of CAM against CAM-susceptible Enterococci strains, and also that of TC against TC-resistant VRE strain s. The present results should encourage research on an ti- bacterial–hydrophilic ingredients derived from Kuma zasa for use against antibiotic-resistant bacteria. The combi- nation of Kumazasa-cytoplasmic extract with a cell wall synthesis inhibitor (ABPC or VCM) will be a highly ef- ficient treatment for infections caused by multidru g-re- sistant MRSA and VRE strains

PURPOSE Sarcoidosis is a heterogeneous and multisystem granulomatous disorder. The etiology still is uncertain, but the disease currently is thought to be triggered by various genetic as well as environmental factors. Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene located in close proximity to the HLA-DRB1 gene was reported. The purpose of our study was to verify the relationship between BTNL2 and HLA risk alleles for the susceptibility to sarcoidosis, and to assess whether the BTNL2 association is independent of the HLA risk alleles. METHODS In our study, 11 single nucleotide polymorphisms (rs28362677, rs2076533, rs2076530, rs2076529, rs2294881, rs3763304, rs2076523, rs28362682, rs3806156, rs9268499, rs3763317), including the functional rs2076530 (G > A) of the BTNL2 gene, and HLA-DRB1 and -DQB1 alleles, were genotyped in 237 Japanese patients diagnosed with sarcoidosis and 287 healthy Japanese control subjects. RESULTS In the patient group, the HLA-DRB1*08:03 (P = 6.15 × 10(-5), odds ratio [OR] = 2.43) and BTNL2 rs2076530_A (P = 6.90 × 10(-6), OR = 1.84) were associated with disease susceptibility. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium between BTNL2 rs2076530_A and HLA-DRB1*08:03, our results suggested that the risk-bearing allele of these two loci interact negatively. No significant differences were observed in allele frequencies for alleles in patients with ocular and other systemic sarcoidosis. CONCLUSIONS Our studies implicated that the HLA-DRB1 allele is a major contributing genetic factor in the development of sarcoidosis in Japan. However, further studies are needed to verify how HLA or BTNL2 alleles confer the disease phenotype, severity of sarcoidosis.

石灰乳ならびに無水塩化アルミニウムを脱塩化水素剤として,液相において各種の塩素化エタンを脱塩化水素し,その生成物ならびに反応性を調べた。CH2Cl・CHCl2を石灰乳で脱塩化水素すると,CH2=CCl2になるが,無水塩化アルミニウムで行なうと,CHCl=CHClとなる。その他の塩素化エタンは脱塩化水素剤として,塩基または酸のいずれを用いても,その分解生成物は同じである。脱塩化水素反応における塩素化エタンの反応性は脱塩化水素剤として塩基を用いた場合には,水素のとれる側の水素が少ないほど,また,塩素のとれる側の塩素が多いほど,増大する。また,脱塩化水素剤として酸を用いた場合には,塩素のとれる側の塩素が多いほど, また, 水素のとれる側の水素が多いほど, 反応性が増大する。

酸化銅-酸化亜鉛触媒を用い,アンモニア:水素:シクロヘキサノール=4:1:1,シクロヘキサノールの仕込み速度0.3～1.0ml/ hr・触媒充てん層ml,温度180～270℃ の条件でシクロヘキサノールの気相アミノ化反応を行なった。主生成物のシクロへキシルアミンの他に,シクロヘキサノン,ジシクロヘキシルアミン,シクロヘキサノンシクロヘキシルイミド等が生成した。これらの副生成物は上記の反応条件では,すべてシクロヘキシルアミンに転化し得る物質であることを確かめた。この気相アミノ化反応は多種類の反応の組合せであるが,まずシクロヘキサノールがシクロヘキサノンに脱水素され,つぎにこのものの還元アミノ化によってシクロヘキシルアミンが生成するものと考えることができる。またシクロヘキサノンとシクロヘキシルアミンの脱水縮合によってシクロヘキサノンシクロヘキシルイミドが生成し,このものの水素添加によってジシクロヘキシルアミンが生成する。さらにジシクロヘキシルアミンとアンモニアとから,2分子のシクロヘキシルアミンの生成する反応もみられる。

シクロヘキサノンをアンモニア水もしくはアルコールのアンモニア溶液中で,ニッケル触媒を用い,温度60～160℃,水素による加圧5kg/cm2以上にて反応せしめると,シクロヘキシルアミンが95%以上の収率で得られた。温度,圧力,反応溶媒の種類と量などの条件の反応速度ならびに生成物の組成に及ぼす影響について詳細に検討した結果,反応速度は,反応液中のシクロヘキサノンの濃度にはほとんど影響されず,触媒濃度と水素分圧とに影響されることを知った。反応機構としては,アンモニアとシクロヘキサノンとが触媒に吸着され,つきに水素添加が進むという考え方が合理的であろう。水溶媒の代りにアルコール溶媒を用いて反応せしめると,反応途中の液にはシクロヘキサノンシクロヘキシルイミドが多量に存在していることを確認した。しかしこのものは,反応終了時にはすべてシクロヘキシルアミンに転化している。

塩化ベンジルを常圧,沸点において,酢酸溶媒中で酸化した場合,臭化コバルト触媒を使用すると,安息香酸を生じ,酢酸ベンジルはほとんど生成しない。一方,酢酸コバルド触媒を使用すると,安息香酸と酢酸ベンジルの混合物が得られる。反応系から酸素をしゃ断すると,塩化ベンジルはコバルトイオン存在のもとで酢酸と反応し,酢酸ベンジルのみを与える。この反応の速度は臭素イオンの存在で低下する。酢酸ベンジルの酸化は酢酸コバルト触媒のみでは進行しない。また,触媒成分として,塩化水素を添加した場合も反応は進行しない。触媒成分として,塩素,臭化水素あるいは,臭素のいずれかを添加すると,反応は進行する。臭化水素および臭素は塩素より触媒効果が強い。

フェニルシクロヘキサンを液相で,常圧あるいは加圧の下に酸素または空気で酸化し,フェニルシクロヘキサンヒドロペルオキシドを得る方法について研究した。フェニルシクロヘキサンは,クメンに比較して酸化を受け難く,またそのヒドロペルオキシドも不安定であるが,水酸化カルシウムあるいは炭酸水素ナトリウム等の弱アルカリ性物質の存在の下では,ヒドロペルオキシドが95%以上の収率でえられた。反応温度は120～100℃の範囲がよいが,反応系のヒドロペルオキシドの濃度の低いうちは,温度は幾分高い方がよい。反応開始剤として,ヒドロペルオキシド自身が役立つ。フェニルシクロヘキサン液相と酸素を含むガスとの接触面を大きくする必要があり,反応系のかきまぜは特に重要である。反応液中のヒドロペルオキシド濃度は10～20%にとめる。これ以上ヒドロペルオキシドの濃度を高くすると,その分解反応が激しくなり,高い収率を得ることが困難であった。

ニッケル触媒を用いるケトン類の還元アミノ化にさいし,シクロヘキサノンやアセトンの場合の反応速度は,ケトンの濃度にはほとんど影響を受けないことはすでに報告した。今回, メチルエチルケトン, メチルイソブチルケトンおよびジエチルケトンについて検討したところ, 反応速度はいずれの場合もケトンの濃度に比例することを知った。主生成物は第一アミンであるが, ジエチルケトンの場合にのみ第ニアミンが多かった。上記ケトンのそれぞれの還元アミノ化反応速度の比はつぎのようであった。シクロヘキサノン:アセトン:メチルエチルケトン:メチルイソブチルケトン:ジエチルケトン=10:10:5.4:5.0:3.8。またこれらのケトンの混合物を還元アミノ化した場合,どのケトンから先に反応するかについてしらべた。この反応性の順位は反応速度の順位とまったく同じで,その比は10:7.1:3.5:2.3:1.3であった。これらの結果から,ケトンの還元アミノ化反応の機構を推定した。

フェニルシクロヘキサンの合成を目的とし,塩化シクロヘキシルとベンゼンとのフリーデル・クラブツ縮合反応を,工業的見地から研究した。フェニルシクロヘキサンの収率に及ぼす反応の条件,たとえば反応系に加えられる塩化シクロヘキシル対ベンゼンのモル比,触媒の濃度,温度,時間などについて検討した。また,この反応の副生物であるジシクロヘキシルベンゼン, トリシクロヘキシルベンゼンなどを, ジスプロポーショネーション反応によって, フェニルシクロヘキサンに変換することができるので,その反応条件を検討した。

アセトンを,水あるいはアルコールを溶媒として,これにアンモニアとニッケル触媒を加え,温度100～180℃,水素による加圧20kg/cm2以上にて反応せしめると,イソプロピルアミンが,90%以上の収率で得られた。温度,触媒量,水素分圧,アンモニア量等の反応条件が,反応速度ならびに反応生成物の組成に及ぼす影響について検討した結果,反応速度は反応液中のアセトンの濃度にはほとんど関係なく,触媒濃度と水素分圧とにほぼ比例することを知った。このことからこの還元アミノ化反応の機構は,すでに報告したシクロヘキサノンの還元アミノ化の場合と同じく,触媒にアンモニアとケトンとが吸着され,それに水素が接触してアミンになるものと考えることができる。また溶媒の種類によって,ニッケル触媒の寿命に差がでてくる。反応液へ触媒のニッケル分が溶出する現象が観察されたが,ニッケル溶出量の多い水溶媒において,触媒の寿命が短かかった。

塩化シクロヘキシルの合成を目的とし,シクロヘキサンの光化学的塩素化反応を研究した。シクロヘキサンおよびその塩素誘導体,(塩化シクロヘキシル,ジクロルシクロヘキサン,トリクロルシクロヘキサン等)は,いずれも反応系において光化学的に塩素化されるが,シクロヘキサン核に塩素原子が1個導入されるごとに,塩素化反応の速度は1/1.7に下がる。塩化シクロヘキシルの収率を高くするためには,反応系において塩素と塩素化誘導体とが衝突する機会を少なくする必要があり,それ以外の反応条件は効果がないことを知った。塩素-シクロヘキサン溶液を暗所で調製し,これを光の照射されている傾斜面に流下させる方法,あるいは,反応生成液中に急速に流入する方法,あるいは,塩酸中に2相に分かれるままに供給する方法が,いずれもよい成績を示した。15%の塩素を含むシクロへキサン溶液をこれらの方法によって処理し,シクロヘキサン基準で,塩化シクロヘキシル収率95%をえることができる。