[Giant Coronary Artery Aneurysm in the Main Trunk of the Coronary Artery].

The case is a 76-year-old woman. She was admitted to the hospital because of chest and back pain. Coronary angiography revealed a 62-mm giant coronary artery aneurysm originating from the left main trunk( LMT), and urgent surgery was performed. Coronary artery-pulmonary artery fistula along with coronary artery aneurysm was completely removed by surgery. In this case, the reconstruction strategy for the LMT was crucial. The aneurysm wall was completely resected, allowing the coronary artery to return to its original course, and the length of the LMT defect was <2 cm. We determined that anatomical reconstruction of the LMT was optimal and succeeded in replacing a short great saphenous vein corresponding to the length of the defect. The patient was discharged without any complications.

Chiral Dinuclear Vanadium Complex-Mediated Oxidative Coupling of Resorcinols.

A method for the highly regio- and enantioselective oxidative coupling of resorcinols has been established by using dibrominated dinuclear vanadium(V) catalyst 1c under air. When resorcinols bearing an aryl substituent were applied as substrates to the coupling, axially chiral biresorcinols were obtained as single regioisomers in high yield with up to 98% ee.

[A case of duodenal neuroendocrine carcinoma composed of small- and large-cell types].

A 78-year-old man underwent a detailed examination by upper gastrointestinal endoscopy for the complaint of epigastric pain. The examination revealed a hemicircumferential type 2 tumor in the descending duodenum. A subsequent biopsy led to a diagnosis of neuroendocrine carcinoma. Subtotal stomach-preserving pancreaticoduodenectomy was performed. The lesion was composed of small- and large-cell neuroendocrine carcinomas. The large-cell type component was positive for both caudal homeobox protein 2 and the cluster of differentiation 138, whereas the small-cell type component was negative for both. Our report may provide valuable information regarding the pathogenesis of neuroendocrine carcinoma.

Brassinolide-like activity of castasterone analogs with varied side chains against rice lamina inclination.

Brassinolide (BL) and castasterone (CS) are the representative members of brassinosteroid class of plant steroid hormone having plant growth promoting activity. In this study, eleven CS analogs bearing a variety of side chains were synthesized to determine the effect of the side chain structures on the BL-like activity. The plant hormonal activity was evaluated in a dwarf rice lamina inclination assay, and the potency was determined as the reciprocal logarithm of the 50% effective dose (ED50) from each dose-response curve. The reciprocal logarithm of ED50 (pED50) was decreased dramatically upon deletion of the C-28 methyl group of CS. The introduction of oxygen-containing groups such as hydroxy, methoxy, and ethoxycarbonyl was also unfavorable to the activity. The pED50 was influenced by the geometry of carbon-carbon double bond between C-24 and C-25 (cis and trans), but the introduction of a fluorine atom at the C-25 position of the double bond did not significantly change the activity. The binding free energy (ΔG) was calculated for all ligand-receptor binding interactions using molecular dynamics, resulting that ΔG is linearly correlated with the pED50.

A case of mixed adenoneuroendocrine carcinoma of the stomach.

A 71-year-old man who tested positive in a pepsinogen test also underwent upper gastrointestinal endoscopy. A 0-IIc lesion was identified at the posterior wall of the antrum. Biopsy findings indicated endocrine cell carcinoma. The patient underwent distal gastrectomy, and subsequent histopathological examination of the resected specimens showed a moderately differentiated adenocarcinoma (tub2) in the mucosa with transformation to small cell carcinoma in the submucosal and muscle layers. The final diagnosis was of a mixed adenoneuroendocrine carcinoma. We herein describe a case report of this patient with this rare form of gastric carcinoma.

[A case of large cell neuroendocrine carcinoma of the rectum].

A 77-year-old woman was referred to our hospital because of blood in feces and anal pain. Colonoscopy revealed a villous semicircular tumor in the rectum. A biopsy showed well-differentiated adenocarcinoma. Miles' operation was performed because of the persistence of anal pain and blood in feces. Histological and immunohistochemical analysis showed coexistent tubulovillous adenoma, tubulovillous adenocarcinoma, and large cell neuroendocrine carcinoma (LCNEC), which was positive for CD56, chromogranin A, and synaptophysin. Pathological examination revealed that most of the lesion was occupied by the LCNEC. The tumor was therefore diagnosed as LCNEC of the rectum. The patient underwent adjuvant chemotherapy with cisplatin (CDDP), irinotecan (CPT-11), and mFOLFOX6, but died because of LCNEC progression 10 months after the operation. LCNEC rarely occurs in the gastrointestinal tract; here we report a case of rectal LCNEC.

Role of polyunsaturated fatty acids in Japanese patients with coronary spastic angina.

BACKGROUND: n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of ischemic heart disease. However, there are few reports of a relationship between n-3 PUFAs and coronary spastic angina (CSA). This study aimed to assess the age-dependent role of serum levels of fatty acid in patients with CSA. METHODS AND RESULTS: We enrolled 406 patients who underwent ergonovine tolerance test (ETT) during coronary angiography for evaluation of CSA. All ETT-positive subjects were diagnosed as having CSA. We categorized the patients by age and results of ETT as follows: (1) young (age ≤ 65 years) CSA-positive (n = 32), (2) young CSA-negative (n = 134), (3) elderly (age > 66 years) CSA-positive (n = 36), and (4) elderly CSA-negative (n = 204) groups. We evaluated the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, and dihomo-gamma-linolenic acid. In the young groups, the serum levels of EPA (64.3 ±â€¯37.7 µg/mL vs. 49.4 ±â€¯28.8 µg/mL, p = 0.015) and DHA (135.7 ±â€¯47.6 µg/mL vs. 117.4 ±â€¯37.6 µg/mL, p = 0.020) were significantly higher in the CSA-positive group than in the CSA-negative group, respectively. However, this was not the case with elderly groups. In the multivariate analysis in young groups, the serum levels of EPA (p = 0.028) and DHA (p = 0.049) were independently associated with the presence of CSA, respectively. CONCLUSION: Our results suggested that the higher serum levels of EPA and/or DHA might be involved in the pathophysiology of CSA in the young population but not in the elderly population.

Investigation of the relationship between ocular sarcoidosis and dry eye.

A relationship between ocular sarcoidosis (OcSar) and dry eye (DE) has previously been reported. Here we investigated the tear function in OcSar, and the other uveitis, Vogt-Koyanagi-Harada disease (VKH), to elucidate the association between OcSar and DE. This study involved 27 eyes of 27 female OcSar patients [mean age: 67.3 ± 13.5 (SD) years], 18 eyes of 18 female VKH patients (53.1 ± 14.1 years), and 17 eyes of 17 female healthy control subjects (59.7 ± 9.6 years). In all examined eyes, tear meniscus height (TMH, mm), fluorescein breakup time (FBUT, s), scoring of keratoconjunctival epithelial damage (ED), and the Schirmer 1 test (ST1, mm/5 min) were analyzed. In the OcSar patients, VKH patients, and control subjects, the respective TMH, FBUT, ED, and ST1 values (mean ± SD) were 0.26 ± 0.10, 0.24 ± 0.09, and 0.24 ± 0.08, 4.3 ± 2.5, 7.3 ± 2.9, and 6.3 ± 3.1, 1.1 ± 1.1, 0.7 ± 0.8, and 0.1 ± 0.3, and 12.9 ± 10.5, 21.5 ± 12.1, and 24.3 ± 10.5. Statistically, the ST1 values were significantly lower in the OcSar patients than in the VKH patients (P = 0.004) and control subjects (P = 0.001). ST1 findings revealed that the neural reflex arc and lacrimal gland system, which attenuate the vicious cycle between the tear film and ocular surface epithelium in DE, are significantly impaired in OcSar cases, thus indicating a possible association between OcSar and DE.

Risk factors for intraocular pressure elevation during the early period post cataract surgery.

PURPOSE: To assess the risk factors for intraocular pressure (IOP) elevation during the early period post cataract surgery. STUDY DESIGN: Retrospective study. METHODS: This study involved 1587 eyes that underwent cataract surgery at the Baptist Eye Institute, Kyoto, Japan between April 2020 and May 2021. In all subjects, risk factors for early postoperative IOP elevation (i.e., an increase of IOP of 10 mmHg or more at 1-day postoperative compared with that at baseline, or a postoperative IOP of 28 mmHg or more) were analyzed by multivariate logistic regression analysis. RESULTS: Of the 1587 treated eyes in this study, 100 (6.3%) experienced early-postoperative IOP elevation. Of those 100 eyes, 78.0% were men, 27.0% had an axial length (AL) of ≥ 26.5 mm, 23.0% had a history of glaucoma treatment, 11.0% had poor mydriasis and 10.0% had intraoperative floppy iris syndrome (IFIS). Multivariate analysis findings revealed that male [odds ratio (OR) 4.36; 95% confidence interval (CI) 2.63-7.23; P < 0.001], AL of ≥ 26.5 mm (3.11; 1.83-5.30; P < 0.001), a history of glaucoma treatment (2.83; 1.63-4.91; P < 0.001), poorly mydriasis (2.63; 1.16-6.01; P = 0.02), IFIS (4.37; 1.78-10.74; P = 0.001) and baseline high IOP (1.09; 1.01-1.18; P = 0.03) were associated with increased IOP during the early period post cataract surgery. CONCLUSIONS: The findings in this study reveal that male sex, high myopia, a history of glaucoma treatment, poor mydriasis, IFIS and baseline high IOP are risk factors for IOP elevation during the early period post cataract surgery.

Current Evidence for Corynebacterium on the Ocular Surface.

Corynebacterium species are commonly found in the conjunctiva of healthy adults and are recognized as non-pathogenic bacteria. In recent years, however, Corynebacterium species have been reported to be potentially pathogenic in various tissues. We investigated Corynebacterium species on the ocular surface and reviewed various species of Corynebacterium in terms of their antimicrobial susceptibility and the underlying molecular resistance mechanisms. We identified a risk for Corynebacterium-related ocular infections in patients with poor immunity, such as patients with diabetes or long-term users of topical steroids, and in those with corneal epithelial damage due to trauma, contact lens wear, lagophthalmos, and trichiasis. The predominant strain in the conjunctiva was C. macginleyi, and the species associated with keratitis and conjunctivitis were C. macginleyi, C. propinquum, C. mastitidis, C. pseudodiphtheriticum, C. accolens, C. striatum, C. xerosis, and C. bovis. Overall, Corynebacterium species present on the ocular surface were resistant to quinolones, whereas those in the nasal cavity were more susceptible. The prevalence of fluoroquinolone-resistant Corynebacterium has not changed in the past 10 years; however, Corynebacterium species remain susceptible to third-generation cephems. In conclusion, the use of third-generation cephems should be a reasonable and pragmatic approach for treatment of ocular infections caused by Corynebacterium species.

A Case of Black Fungal Keratitis Caused by Biatriospora mackinnonii.

PURPOSE: To report a novel case of fungal keratitis caused by Biatriospora mackinnonii (Pyrenochaeta mackinnonii), a dematiaceous fungus (black fungus) that rarely causes dermatological infection, in a patient treated for ocular cicatricial pemphigoid. METHODS: An 81-year-old patient with ocular cicatricial pemphigoid was referred to our hospital because of persistent corneal epithelial defects in his left eye. On examination, a slightly elevated dark lesion in the middle of the erosion and hypopyon was observed in that eye, with smear examination of the obtained specimen revealed a filamentous fungal-like material. Initially, treatment included miconazole and fluconazole ophthalmic solution eye drops, natamycin ophthalmic ointment, and systemic voriconazole, followed surgical scraping of the mass, an anterior chamber lavage, and a subconjunctival injection of miconazole. However, the focus had resistance to the treatment and finally led to corneal perforation; hence, therapeutic penetrating keratoplasty (PKP) was subsequently performed. RESULTS: Mycological testing revealed that the lesions were Candida parapsiliosis and black fungus, with the black fungus classified as B. mackinnonii via DNA sequencing of the internal transcribed spacer and the D1/D2 domains of the 28S rRNA gene. Fungal keratitis caused by B. mackinnonii was resistant to the antifungal drugs, yet was ameliorated by PKP, with no recurrence of fungal keratitis for more than 2 years postoperative. CONCLUSIONS: To the best of our knowledge, this is the first reported case of fungal keratitis caused by B. mackinnonii; however, in this case, PKP surgery resulted in a favorable outcome.

Prediction Error of Intraocular Lens Power Calculation in Very Elderly Patients over 90 Years Old.

BACKGROUND: To investigate the influence of age on prediction error (PE) after cataract surgery in very elderly (VE) patients aged more than 90 years. METHODS: We retrospectively analyzed 66 eyes of patients aged ≥90 years (VE group) who underwent phacoemulsification and intraocular lens (IOL) implantation. As the control group (CG), we investigated 121 eyes of patients aged 70-89 years who underwent the same surgery. PE was calculated 1 month post-surgery as the actual postoperative spherical equivalent minus the target diopter, which was calculated using the Sanders-Retzlaff-Kraff/T formula. The absolute and arithmetic PE were compared between the two groups. The factors affecting absolute PE outside ±0.5 diopter (D) and ±1.0 D were determined through logistic regression analysis with the variables age, sex, axial length (AL), average corneal power, preoperative best-corrected visual acuity, target diopter, and coexisting pseudoexfoliation syndrome. RESULTS: The absolute PE was significantly larger in the VE group than that in the CG (0.60 ± 0.52 D and 0.34 ± 0.25 D, respectively; P < .001). There was no significant difference in terms of arithmetic PE between the two groups (-0.06 ± 0.79 D and -0.07 ± 0.42 D, respectively; P = .653). In the logistic regression analysis, age was significantly associated with absolute PE outside ±0.50 D (Odds ratio [OR]: 1.05). Age and AL were significantly associated with absolute PE outside ±1.0 D (OR: 1.24 and 0.20, respectively). CONCLUSIONS: Absolute PE tended to increase in the cataract surgery of VE patients.

Risk Factors for Corneal Endothelial Cell Loss in Patients with Pseudoexfoliation Syndrome.

This study investigated corneal endothelial cell density (ECD) in pseudoexfoliation (PEX) syndrome patients and evaluated the clinical factors associated with ECD for 51 eyes of 41 phakic patients with pseudoexfoliation (PEX group) and 201 eyes of 117 patients with age-related cataracts (control group) as an age-matched control to the PEX group. Variable clinical factors, including ECD, central corneal thickness (CCT), anterior chamber depth (ACD), number of anti-glaucoma eye drops and severity of PEX, were examined using multivariate analyses. Severity of PEX was as follows: Mild in 28 eyes, Moderate in 16 eyes, and Severe in 7 eyes. The mean ECD was 2,548 ± 409 cells/mm2 in the PEX group and 2,757 ± 282 cells/mm2 in the control group, respectively, and ECD in the PEX group was significantly lower than that in the control group (P = 0.02). Multivariate analyses revealed that the severity of PEX [-176.8, 95% confidence interval (CI) (-244.5, -109.2), P < 0.01] was significantly associated with lower ECD. Accumulation of PEX materials contributed to early corneal endothelial decompensation.

Publisher Correction: Risk Factors for Corneal Endothelial Cell Loss in Patients with Pseudoexfoliation Syndrome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Metabolism-dependent hepatotoxicity of amodiaquine in glutathione-depleted mice.

We investigated the hepatotoxicity induced by AQ using a glutathione (GSH)-depleted mice model. Although sole administration of either AQ or L-buthionine-S,R-sulfoxinine (BSO), a well-known GSH synthesis inhibitor, produced no significant hepatotoxicity, combined administration of AQ with BSO induced hepatotoxicity characterized by centrilobular necrosis of the hepatocytes and an elevation of plasma alanine aminotransferase activity. Pretreatment of aminobenzotriazole, a nonspecific inhibitor for P450s, completely suppressed the above hepatotoxicity caused by AQ co-treatment with BSO. Administration of radiolabeled AQ in combination with BSO exhibited significantly higher covalent binding to mice liver proteins than that observed after sole dosing of radiolabeled AQ. The results obtained in this GSH-depleted animal model suggest that the reactive metabolite of AQ formed by hepatic P450 binds to liver proteins, and then finally leads to hepatotoxicity. These observations may help to understand the risk factors and the mechanism for idiosyncratic hepatotoxicity of AQ in humans.

[A case in which intra-arterial chemotherapy for simultaneous hepatic metastases markedly improved AFP-producing gastric cancer].

The prognosis of most hepatic and lymph node metastases in AFP-producing gastric cancer is poor, and despite the use of multimodal therapy, the average survival period is reported to be approximately one year. Described here is one example in which intra-arterial chemotherapy for simultaneous hepatic metastases in AFP-producing gastric cancer achieved a marked improvement. The patient is a 65-year-old female. Distal gastrectomy was performed for Type II gastric cancer. L, type 2, 5.5x2.4 cm, tub 2>por 1, pT2 (MP), int, INF b, ly2, v1, pN1, pPM (-), pDM (-), pH1: stage IV. The AFP level before surgery was 801.4 ng/mL and lowered to 65.8 ng/mL after surgery, AFP-producing gastric cancer and simultaneous hepatic metastases (S4, single lesion) was diagnosed based upon imaging examinations. 5-FU+epirubicin+MMC (FEM)intra-arterial chemotherapy was started one month following surgery, but because CT showed multiple new hepatic lesions(S4, S5)four months following surgery, DSM therapy was performed with hepatic arterial injections of MMC 10 mg, DSM 300 mg. Dynamic CT showed a reduction in size of the tumors in both S4 and S5, and at five months following surgery, hepatic arterial infusion chemotherapy FP (CDDP 5 mg+5-FU 250 mg weekly) was started and performed 45 times in a 14-month period. During therapy, CR was achieved for the hepatic metastases and tumor marker levels were also normal. Because an introduction of contrast medium into the hepatic reservoir showed a narrowing of the hepatic artery and inflow of contrast medium into the splenic artery, arterial infusion was terminated. Following this, from the 20th month following surgery, S-1 (100 mg/day: 4 weeks administration, 2 weeks rest) was started and from the third course (50 mg/ day: 4 weeks administration, 2 weeks rest), and the patient is currently undergoing a sixth course. Currently, 2 years and 4 months after surgery, there have been no recurrences. This suggests the possibility that intra-arterial chemotherapy is an effective treatment method for hepatic metastases in AFP-producing gastric cancer.

[S-1+gemcitabine (GEM) therapy was effective in a case of unresectable pancreatic head carcinoma].

OBJECTIVE: Treatment results of pancreatic head carcinoma are not good and long-term survival, especially in nonresectable cases is extremely difficult to obtain. The case reported here is of nonresectable pancreatic head carcinoma in which S-1+gemcitabine (GEM) proved to be effective. CASE: A 70-year-old male. The patient initially complained of epigastralgia. Jaundice was also noted and upon further study, pancreatic head carcinoma, portal vein and common hepatic artery infiltration along with duodenal infiltration were diagnosed. Gastrojejunostomy and cholecystectomy were performed with a preoperative diagnosis of Phb, TS2 infiltrative type T4, CH (+), DU (+), S (+), RP (-), PV (+), Ach (+), PLX, OO (-), N0, M0, and Stage IVa. Perioperative findings showed no hepatic or peritoneal metastases. Following surgery, S-1+ GEM (S-1 100 mg/day, day 1-14; GEM 1,000 mg/m(2) was administered on day 8 and day 15 for 2 weeks followed by one week of no administration) was started. After completing 2 courses, there was no change in the tumor, but after finishing the sixth course, there was a notable reduction in tumor size, and after finishing the 10th course, a further reduction was noted. Currently at the end of the 14th course, the tumors are unidentifiable upon imaging. At 1 year and 5 months from the initial diagnosis, there has been no recurrence and chemotherapy is being continued. In the case reported here, there have been no adverse side-effects from the S-1+GEM therapy, it is a safe method which does not lower QOL in patients with unresectable pancreatic carcinoma, and we can look forward to the possibility of extended survival times. CONCLUSION: In the case of unresectable pancreatic carcinoma, S-1+GEM therapy may be able to provide an improved long-term prognosis.

Rectal mucocele in the anterior wall of the rectum.

An 84-year-old man presented in 2009 with a sensation of discomfort in his anus, combined with difficulty in urination. He had previously undergone a haemorrhoidectomy in 1964. After examination, he was diagnosed with a rectal mucosal cyst and followed up for observation. In 2015, he presented to our hospital complaining that the cyst was prolapsing from his anus. CT revealed a 48×41 mm cystic mass in the anterior wall of the rectum. Tumour extirpation, via a transanal route, was performed. The postoperative pathological diagnosis confirmed a rectal mucocele. Rectal mucoceles are extremely rare, with no prior report of a mucocele in the anterior wall of the rectum. In this case, we believe the mucocele developed from an invagination of the mucous membrane or obstruction of the anal gland during suturing during the previous haemorrhoid surgery.

Tissue inhibitors of metalloproteinases-1 (TIMP-1) and -2(TIMP-2) are major serum factors that stimulate the TIMP-1 gene in human gingival fibroblasts.

We demonstrate in this study that both TIMP-1 and TIMP-2 are major serum factors that stimulate the induction of TIMP-1 mRNA in quiescent human gingival fibroblasts (Gin-1 cells) at mid-G1 (6-9 h after serum stimulation) of the cell cycle, but not that of TIMP-2. When we chased the secretion of both TIMP proteins into culture medium containing 10% FCS freed of both TIMPs, TIMP-2 secretion rose to the level in 10% FCS after 24 h, but TIMP-1 secretion remained at a fairly low level even after 3 days, thus reflecting a contrastive difference in the induction of both TIMP mRNAs. The stimulating activity of TIMP-1 on the expression of the TIMP-1 gene switched over to inhibitory activity, when the TIMP-1 concentration in the culture medium exceeded about 30 ng/ml. The depletion of TIMP-1 and TIMP-2 from FCS affected remarkably the induction of c-jun and c-fos mRNAs, but not that of c-ets-1 mRNA. TIMP-1 and TIMP-2-dependent expression of AP-1 protein was further demonstrated by using nuclear extracts of Gin-1 cells in an electrophoretic mobility shift assay.

Tumor targeting of doxorubicin by anti-MT1-MMP antibody-modified PEG liposomes.

Immunoliposomes are potent carriers for targeting of therapeutic drugs to specific cells. Membrane type-1 matrix metalloproteinase (MT1-MMP), which plays an important role in angiogenesis, is expressed on angiogenic endothelium cells as well as tumor cells. Then, the MT1-MMP might be useful as a target molecule for tumor and neovascularity. In the present study, we addressed a utility of antibodies against the MT1-MMP as a targeting ligand of liposomal anticancer drug. Fab' fragments of antibody against the MT1-MMP were modified at distal end of polyethylene glycol (PEG) of doxorubicin (DXR)-encapsulating liposomes, DXR-sterically stabilized immunoliposomes (DXR-SIL[anti-MT1-MMP(Fab')]). Modification with the antibody significantly enhanced cellular uptake of DXR-SIL[anti-MT1-MMP(Fab')] into the HT1080 cells, which highly express MT1-MMP, compared with the non-targeted liposomes (DXR-stealthliposomes (DXR-SL)), suggesting that MT1-MMP antibody (Fab') is a potent targeting ligand for the MT1-MMP expressed cells. In vivo systemic administration of DXR-SIL[anti-MT1-MMP(Fab')] into the tumor-bearing mice showed significant suppression of tumor growth compared to DXR-SL. This is presumably due to the active targeting of immunoliposomes for tumor and neovascularity. However, tumor accumulation of DXR-SIL[anti-MT1-MMP(Fab')] and DXR-SL were comparable, suggesting that both liposomal formulations accumulated in tumor via enhanced permeation and retention (EPR) effect, but not via targeting to the MT1-MMP expressed on both the endothelial and tumor cells. It appears that the enhanced antitumor activity of DXR-SIL[anti-MT1-MMP(Fab')] resulted from acceleration of cellular uptake of lioposomes owing to the incorporated antibody after extravasation from capillaries in tumor.