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Surgical fixation after recurrent regurgitation following surgical mitral repair has been technically demanding and associated with high morbidity and mortality. Avoiding reopening the adhesive site or limiting the usage of cardiopulmonary bypass are solutions for reducing the operative risk. We report a case of recurrent mitral regurgitation treated by off-pump neochordae implantation via left minithoracotomy. A 69-year-old woman with a history of conventional mitral repair via median sternotomy developed heart failure due to mitral regurgitation from recurrent posterior leaflet P2 prolapse. Four neochordaes were implanted off-pump via left minithoracotomy using a NeoChord DS1000 in the seventh intercostal space. No transfusion was required. The patient was discharged a week after the procedure with no complications. The regurgitation remains trivial 6 months after the NeoChord procedure.

The direct 4-alkoxylation of 4-iodo-1 H -pyrazoles with alcohols was achieved by a CuI-catalyzed coupling protocol. The optimal reaction conditions employed excess alcohol and potassium t -butoxide (2 equiv) in the presence of CuI (20 mol%) and 3,4,7,8-tetramethyl-1,10-phenanthroline (20 mol%) at 130 °C for 1 h under microwave irradiation. The present method was efficiently applied to the synthesis of withasomnine and its six- and seven-membered cyclic homologs.

Purpose: In clinical practice, whether cirrhotic livers in patients with hepatocellular carcinoma (HCC) can withstand repeated stereotactic body radiation therapy (SBRT) remains unclear. This study aimed to evaluate the outcomes and toxicities in these patients., Methods and Materials: This retrospective study included patients with HCC who were treated with SBRT at least twice between January 2012 and June 2019. Local control and overall survival rates were calculated. Liver function before and after irradiation was evaluated using the Child-Pugh score and modified albumin-bilirubin grade. All toxicities were assessed using the Common Terminology Criteria for Adverse Events (version 4.0)., Results: Fifty-two patients underwent 136 courses (148 lesions) of SBRT, which was mostly performed for out-of-field tumors but 3 in-field recurrences. The median follow-up duration from the first SBRT was 52.6 months (range, 15.7-89.3 months). The median gross tumor volume was 4.6 cm 3 (range, 0.8-55.2 cm 3 ) at the second SBRT. The 3-year local control rate was 94.5% (95% confidence interval, 88.0%-97.5%). The 3-year overall survival rate after the second course was 62.8% (95% confidence interval, 45.1%-76.2%). Although the Child-Pugh score did not deteriorate after the second course, deterioration of the modified albumin-bilirubin grade at 6, 12, and 24 months was statistically significant compared with that before the second course. One patient (1.9%) experienced grade 3 hypoalbuminemia and 2 patients (3.8%) had grade 3 thrombocytopenia 6 months after the second course. Mild fatigue and nausea were reported in 9 (17.3%) and 6 (11.5%) patients, respectively. One instance of grade 5 toxicity was observed. Two patients (1.5%) had grade 2 gastric ulcers. No other grade ≥3 gastrointestinal toxicities occurred., Conclusions: Repeated SBRT is feasible and produces minimal toxicity in patients with HCC and Child-Pugh scores of ≤7 and a low normal liver dose., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Objective : The bone scan plays an important role for detecting number of conditions relating to bones, including: bone cancer or bone metastasis, bone inflammation. Extraosseous uptake, in particular, myocardial uptake, was observed in some patients examined with the bone scans. Positive uptake of 99m Tc-labeled bone radiotracers is associated with cardiac amyloidosis. However, the frequency and cause of positive cardiac 99m Tc-MDP uptake have not been fully studied. In this regard, the aim of this study was to assess the frequency and characteristics of patients with high myocardi-al uptake of bone scintigraphy in daily clinical practice setting. Methods : We retrospectively analyzed 4180 bone scintigraphies performed in daily clinical practice during 7-years period. The intensity of the myocardial uptake was graded based on a visual scale ranging from 0 to 3 points. Score 0 indicates the absence of uptake. Score 1 defined uptake less than that of bone (referred to as the adjacent rib). Uptake similar to that of bone was classified score 2. Score 3 was defined as uptake greater than that of reference bone. Positive myocardial uptake included a visual score 2 or 3. Result : Positive 99m Tc-MDP myocardial uptake occurred in 12 patients among 4180 patients (0.3%). 7 of 12 positive scan patients were consistent with amyloidosis confirmed by biopsy. In these patients, the mean age was 75.6 ± 5.2 years old. Ten cases showed biventricular uptake and 2 showed LV uptake only. Conclusion : Positive cardiac uptake of bone scintigraphic agents was present in 0.3% of bone scintigraphies in a clinical practice setting. This may be a sign of cardiac amyloidosis involvement which may give the presence of extraosseous bone tracer uptake its own importance and a new role., Competing Interests: The authors have no financial conflicts of interest to disclose concerning this study., (© The Japanese Society of Nuclear Cardiology 2020.)

Purpose: To broaden the current understanding of radiation exposure and risk and to provide concrete evidence of radiation safety related to (125)I seed implantation., Methods and Materials: Direct radiation exposure measurements were obtained from dosimeters provided to 25 patients who underwent (125)I seed implantation, along with their family members. The estimated lifetime exposure dose and the precaution time for holding children near the patient's chest were calculated in two study periods., Results: During the first and second study period, the mean estimated lifetime exposure doses were, respectively, 7.61 (range: 0.45, 20.21) mSv and 6.84 (range: 0.41, 19.20) mSv for patients, and 0.19 (range: 0.02, 0.54) mSv and 0.25 (range: 0.04, 1.00) mSv for family members. The mean ratios of first and second period measurements were 1.05 (range: 0.44, 3.18) for patients and 1.82 (range: 0.21, 7.04) for family members. The corresponding absolute differences between first and second period measurements were -0.77 (range: -11.40, 7.63) mSv and 0.06 (range: -0.26, 0.79) mSv, respectively. Assuming a dose limit of 1 mSv, the precaution times for holding a child every day of the first and second periods were 250.9 (range: 71.3, 849.4) min and 275.2 (range: 75.0, 883.4) min, respectively. Assuming a dose limit of 0.5 mSv, the corresponding precaution times were 179.0 (range: 35.6, 811.5) min and 178.9 (range: 37.5, 1131.8) min, respectively., Conclusions: Our study demonstrated low radiation exposures to family members of patients undergoing (125)I prostate implantation. It was clear that (125)I seed implantation did not pose a threat to the safety of family members., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the structural changes of the choroid in eyes with central serous chorioretinopathy (CSC) by enhanced depth imaging optical coherence tomography (EDI-OCT)., Methods: A retrospective comparative study was performed at two academic institutions. Forty eyes with CSC, their fellow eyes, and 40 eyes of age-matched controls were studied. Subfoveal cross sectional EDI-OCT images were recorded, and the hypo reflective and hyperreflective areas of the inner and outer choroid in the EDI-OCT images were separately measured. The images were analyzed by a binarization method to determine the sizes of the hyporeflective and hyperreflective areas., Results: In the inner choroid, the hyperreflective area was significantly larger in the CSC eyes (35,640±10,229 μm2) than the fellow eyes (22,908±8,522 μm2) and the control eyes (20,630±8,128 μm2; P<0.01 vs control for both, Wilcoxon signed-rank test). In the outer choroid, the hyporeflective area was significantly larger in the CSC eyes (446,549±121,214 μm2) than the control eyes (235,680±97,352 μm2, P<0.01). The average ratio of the hyporeflective area to the total choroidal area was smaller in the CSC eyes (67.0%) than the fellow eyes (76.5%) and the control eyes (76.7%) in the inner choroid (P<0.01, both). However, the ratio was larger in the CSC eyes (75.2%) and fellow eyes (71.7%) than in the control eyes (64.7%) in the outer choroid (P<0.01, both)., Conclusions: The larger hyperreflective area in the inner choroid is related to the inflammation and edema of the stroma of the choroid in the acute stage of CSC. The larger hyporeflective areas in the outer choroid is due to a dilatation of the vascular lumens of the larger blood vessels. These are the essential characteristics of eyes with CSC regardless of the onset.

Purpose: We examined the factors associated with urinary toxicities because of brachytherapy with iodine-125 with or without supplemental external beam radiotherapy (EBRT) for prostate cancer., Methods and Materials: We investigated 1313 patients with localized prostate cancer treated with iodine-125 brachytherapy with or without supplemental EBRT between 2003 and 2009. The International Prostate Symptom Score (IPSS) and Common Terminology Criteria for Adverse Events data were prospectively determined. Patients, treatment, and implant factors were investigated for their association with urinary toxicity or symptoms., Results: IPSS resolution was not associated with biologically effective dose (BED). Baseline IPSS, total needles, and the minimal dose received by 30% of the urethra had the greatest effect according to multivariate analysis (MVA). Urinary symptom flare was associated with baseline IPSS, age, BED, and EBRT on MVA. Urinary symptom flare and urinary Grade 2 or higher (G2+) toxicity occurred in 51%, 58%, and 67% (p = 0.025) and 16%, 22%, and 20% (p = 0.497) of the <180, 180-220, and >220 Gy BED groups, respectively. Urinary G2+ toxicity was associated with baseline IPSS, neoadjuvant androgen deprivation therapy (NADT), and seed density on MVA. When we divided patients into four groups according to prostate volume (<30 cc or ≥30 cc) and NADT use, urinary G2+ toxicity was most commonly observed in those patients with larger prostates who received NADT, and least in the patients with smaller prostates and no NADT., Conclusions: NADT was associated with urinary G2+ toxicity. Higher dose and supplemental EBRT did not appear to increase moderate to severe urinary toxicities or time to IPSS resolution; however, it influenced urinary symptom flare., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To report outcomes for men treated with iodine-125 ((125)I) prostate brachytherapy (BT) at a single institution in Japan., Methods and Materials: Between 2003 and 2009, 1313 patients (median age, 68 years) with clinically localized prostate cancer were treated with (125)I BT. Median prostate-specific antigen level was 7.6 ng/mL (range, 1.1-43.3). T-stage was T1c in 60%, T2 in 39%, and T3 in 1% of patients. The Gleason score was <7, 7, and >7 in 49%, 45%, and 6% of patients, respectively. Neoadjuvant androgen deprivation therapy was used in 40% of patients and combined external beam radiotherapy of 45 Gy in 48% of patients. Postimplant dosimetry was performed after 30 days after implantation, with total doses converted to the biologically effective dose. Survival functions were calculated by the Kaplan-Meier method and Cox hazard model., Results: Median followup was 67 months (range, 6-126). The 7-year biochemical freedom from failure for low-, intermediate-, and selected high-risk prostate cancers were 98%, 93%, and 81%, respectively (p < 0.001). Multivariate analysis identified the Gleason score, initial prostate-specific antigen level, positive biopsy rate, dose, and neoadjuvant androgen deprivation therapy as predictors for biochemical freedom from failure. The 7-year actuarial developing Grade 3+ genitourinary and gastrointestinal toxicity was 2% and 0.3%, respectively. Forty-four percent patients with normal baseline potency retained normal erectile function at 5 years., Conclusions: (125)I prostate BT is a highly effective treatment option for low-, intermediate-, and selected high-risk prostate cancers. Side effects were tolerable. An adequate dose may be required to achieve successful biochemical control., (Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

A 59-year-old man with inferior acute myocardial infarction underwent an urgent coronary angiography and as a result a total occlusion of the ostial right coronary artery (RCA) was observed. Interestingly, the thrombus in the RCA clearly shortened within 2.3 s during the contrast media injection. While we prepared for percutaneous coronary intervention (PCI) of the RCA, ventricular fibrillation occurred and pulseless electrical activity continued in spite of repeated cardioversion. Despite no stenosis in the left main trunk (LMT) in the initial coronary angiography, the LMT was totally occluded. Following aspiration therapy on the LMT with percutaneous cardiopulmonary support, PCI of the RCA was performed. A coronary angiography should be carefully performed if a lot of thrombi exist in the coronary ostium because LMT embolism may have been caused by thrombus extraction from the RCA by contrast media injection.

Background: We report a case of intraocular lymphoma that developed macular edema and cotton wool spots after treatment with intravitreal methotrexate., Case: A 56-year-old woman presented with blurred vision OU. Twelve months prior, she had been diagnosed with primary central nervous system lymphoma. She was in remission after high-dose methotrexate therapy and whole brain radiation therapy. Fundus examination demonstrated bilateral vitreous opacities and subretinal lesions and she was diagnosed with intraocular lymphoma by vitreous biopsy. After treatment with intavitreal methotrexate the subretinal lesions disappeared, but corneal epitheliopathy, macular edema, and cotton wool spots appeared in both eyes. After stopping the intravitreal methotrexate, the corneal epitheliopathy resolved rapidly, but the macular edema and cotton-wool spots remained. These findings disappeared gradually after a posterior sub-Tenon injection of triamcinolone acetonide. Although there was no recurrence of the intraocular lymphoma for 16 months, the patient died from a relapse of the central nervous system lymphoma., Conclusions: The use of intravitreal methotrexate after radiation therapy may be associated with adverse events in the retina, including possible radiation retinopathy.

We report a case of unresectable gastric cancer, who had been treated with S-1 alone for 3 years without cancerous symptoms. The patient was a 66-year-old male. His diagnosis was advanced gastric cancer based on gastrofiberscopy. He underwent surgery on April 15, 2003. The tumor proved to be unresectable due to direct invasion of the pancreatic head, so only gastrojejunostomy was performed. On day 14 after surgery, the administration of S-1 alone was commenced at a dose of 100 mg per day in a 4-week course of medication at 2-week intervals. No side effects were noted. Moreover, his quality of life (QOL) was not disturbed, and he led an active social life throughout the course. Long survival was achieved by S-1 alone.

Carbon nanotubes hold great promise for use in biomedical fields. Among numerous potential applications, including DNA and protein sensors, bioseparators, biocatalysts, and tissue scaffolds, this article emphasizes the use of carbon-nanotube-filled polymer composites as medical devices, namely, microcatheters. The currently hot topic of the biocompatibility (e.g., toxic properties) of carbon nanotubes is discussed. In addition, critical issues that must be clarified for the full utilization of current carbon-nanotube science and technology in biomedical fields are discussed.

We applied serological analysis of recombinant cDNA expression libraries (SEREX) to cases of esophageal squamous cell carcinoma (SCC) to identify tumor antigens. One of the clones identified was TROP2, which is known as calcium signal transducer. To evaluate the clinical significance of serum anti-TROP2 antibodies (s-TROP2-Abs) in patients with esophageal SCC, the presence of s-TROP2-Abs was analyzed by Western blotting using bacterially expressed TROP2 protein. We found that 23 of 75 (31%) patients were positive for s-TROP2-Abs. Positivity in terms of s-TROP2-Abs showed a significant association with tumor size but not with other clinicopathological features. The protein expression levels of TROP2 were much higher in esophageal SCC cell lines as compared to those in normal esophageal mucosa and its immortalized cells although the mRNA expression levels were not necessarily elevated in malignant cell lines and tissues. Immunohistochemical studies showed that the expression of TROP2 protein in esophageal SCC specimens was noticeably higher than that found in mild hyperplasia of esophageal mucosae. Thus, s-TROP2-Abs seemed useful in the diagnosis of SCC and may be a candidate for serum tumor markers., ((c) 2004 Wiley-Liss, Inc.)

A second lysyl endopeptidase gene (lepB) was found immediately upstream of the previously isolated lepA gene encoding a highly active lysyl endopeptidase in Lysobacter genomic DNA. The lepB gene consists of 2,034 nucleotides coding for a protein of 678 amino acids. Amino acid sequence alignment between the lepA and lepB gene products (LepA and LepB) revealed that the LepB precursor protein is composed of a prepeptide (20 amino acids [aa]), a propeptide (184 aa), a mature enzyme (274 aa), and a C-terminal extension peptide (200 aa). The mature enzyme region exhibited 72% sequence identity to its LepA counterpart and conserved all essential amino acids constituting the catalytic triad and the primary determining site for lysine specificity. The lepB gene encoding the propeptide and mature-enzyme portions was overexpressed in Escherichia coli, and the inclusion body produced generated active LepB through appropriate refolding and processing. The purified enzyme, a mature 274-aa lysine-specific endopeptidase, was less active and more sensitive to both temperature and denaturation with urea, guanidine hydrochloride, or sodium dodecyl sulfate than LepA. LepA-based modeling implies that LepB can fold into essentially the same three-dimensional structure as LepA by placing a peptide segment, composed of several inserted amino acids found only in LepB, outside the molecule and that the Tyr169 side chain occupies the site in which the indole ring of Trp169, a built-in modulator for unique peptidase functions of LepA, resides. The results suggest that LepB is an isozyme of LepA and probably has a tertiary structure quite similar to it.

We have developed a method that we call 'drug-sensitivity pattern analysis', or DSPA, for analysis of protein function. Cells are transfected with cDNA of the test molecule, followed by analysis of the sensitivity of the transfected cells to multiple growth-inhibitory drugs. If two cDNA products have similar functions, their transfected cells should show similar drug-sensitivity patterns. The cDNAs of some signaling molecules were transfected into NIH3T3 or Ha-ras-transformed NIH3T3 (ras-NIH) cells and stable transfectants, which expressed high amounts of the gene product, were isolated. Chemosensitivity of the transfected clone was compared with the parental cells by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method using more than 40 drugs. The chemosensitivity changes caused by the transfected gene were calculated and expressed numerically as 'drug chemosensitivity index' (DCI). When the DCI values were analyzed by regression analysis, a significant positive relationship between IkappaBalpha superrepressor and dominant-negative IKKbeta and an inverse relationship between p53 and Mdm2 were consistent with previous reports. Thus, the DSPA method is useful for identifying functional similarities between gene products.

Thymidine kinase (TK) is a protein closely associated with DNA replication. Here we show that, in contrast with the variation of TK activity, which changed parallel with S phase cell distribution during asynchronous culture of rat hepatoma JB1 cells, the serine residues of cytosolic TK protein was phosphorylated continuously in response to increasing G0/G1 phase cell distribution. The shifting of phosphorylation of TK protein during different cell growth conditions was further confirmed with the examination of the elution profile of cytosolic TK activity by anion-exchange high performance liquid chromatography (HPLC). HPLC analysis revealed that the rapid proliferating (62 h after asynchronous culture) rat hepatoma JB1 cells showed only the hyperphosphorylated form of cytosolic TK activity, while synchronously M phase-arrested JB1 cells showed hypo- and hyper-phosphorylated forms of cytosolic TK activity. These results suggested that the modulation of phosphorylation of cytosolic TK protein was cell cycle-dependent, and that the phosphorylation of cytosolic TK protein might be involved in the negative regulation of TK activity in vivo.

A nuclear criticality accident occurred in Japan on September 30, 1999, which resulted in severe exposure of three victims to mixed flux of neutrons and gamma-rays. Estimated average doses for the three victims were 5.4 Gy of neutrons and 8.5 Gy of gamma-rays for Patient A, 2.9 Gy of neutrons and 4.5 Gy of gamma-rays for Patient B, and 0.81 Gy of neutrons and 1.3 Gy of gamma-rays for Patient C. They then suffered the consequences of the effects of ionizing radiation resulting in acute radiation syndrome. In Patients A and B, bone marrow failure was so severe that they received haematopoietic stem cell transplantation. The graft initially took successfully in both patients, although in Patient B it was later taken over by his own haematopoietic cells. They also suffered from severe skin lesions, later exhibited gastrointestinal bleeding and eventually died of multiple organ failure 82 and 210 days after the accident, respectively. The survival of these patients beyond the period of agranulocytosis means that bone marrow failure per se caused by exposure to ionizing radiation may now be overcome. Patient C also developed bone marrow failure and was treated with granulocyte colony-stimulating factor as well as supportive care. He recovered without major complications and is now under periodical follow-up. Remarkably, during the prodromal phase, all the patients exhibited hypoxaemia, two of whom also showed interstitial oedema of the lungs. In Patient C these manifestations improved within a week. The circumstances of the accident and the initial medical treatment of the victims are described.

Arginase in salivary glands is potentially involved in the synthesis of proline, glutamate, and polyamines that play specific physiological roles in the glands, and also in depletion of arginine in the oral cavity to protect teeth from microorganisms. We detected protein and mRNA for the type I isoform of arginase in mouse salivary glands. Enzymes of the arginine-biosynthetic pathway were also detected. Immunohistochemical analysis revealed that arginase I was enriched in the striated duct, and was also present in the acinus, demilune and granulated duct. Mice with targeted disruption of the gene for C/EBPalpha, which is a transcription factor essential for expression of the arginase I gene in the liver, showed dramatically reduced immunoreactivity for arginase I in the parotid gland but not in the submandibular and sublingual glands. Therefore, C/EBPalpha is specifically required for expression of the arginase I gene in the parotid gland.

A criticality accident occurred on September 30, 1999, at the uranium conversion plant in Tokai-mura (Tokai-village), Ibaraki Prefecture, Japan. When the criticality occurred, three workers saw a "blue-white glow," and a radiation monitor alarm was sounded. They were severely exposed to neutron and gamma-ray irradiation, and subsequently developed acute radiation syndrome (ARS). One worker reported vomiting within minutes and loss of consciousness for 10-20 seconds. This worker also had diarrhea an hour after the exposure. The other worker started to vomit almost an hour after the exposure. The three workers, including their supervisor, who had no symptoms at the time, were brought to the National Mito Hospital by ambulance. Because of the detection of gamma-rays from their body surface by preliminary surveys and decreased numbers of lymphocytes in peripheral blood, they were transferred to the National Institute of Radiological Sciences (NIRS), which has been designated as a hospital responsible for radiation emergencies. Dose estimations for the three workers were performed by prodromal symptoms, serial changes of lymphocyte numbers, chromosomal analysis, and 24Na activity. The results obtained from these methods were fairly consistent. Most of the data, such as the dose rate of radiation, its distribution, and the quality needed to evaluate the average dose, were not available when the decision for hematopoitic stem cell transplantation had to be made. Therefore, prodromal symptoms may be important in making decisions for therapeutic strategies, such as stem-cell transplantation in heavily exposed victims.

Clofibrate-induced retrograde Golgi membrane movement was blocked or retarded when NRK cells were treated with sodium azide/2-deoxyglucose, nocodazole, taxol, and destruxin B, indicating that it depends on energy, and the dynamic state of microtubules, and being acidic or vacuolar-type ATPase function. PDMP and phospholipase A2 inhibitors also blocked it. These characteristics are similar to those of brefeldin A (BFA) and nordihydroguaiaretic acid (NDGA), inducers of retrograde Golgi membrane movement. However, clofibrate was distinguished from BFA in that BFA action was insensitive to phospholipase A2 inhibitors and from NDGA in that NDGA stabilized microtubules against nocodazole and its action was almost insensitive to taxol. The trans Golgi network (TGN) was resistant to clofibrate, while BFA and NDGA dispersed it. To our knowledge, clofibrate is the first drug to show such different effects on the Golgi and TGN and, therefore, is expected to be a useful tool to distinguish their architecture and/or membrane dynamics.

Anti-TK monoclonal antibodies (mAbs) were raised against recombinant human cytosolic thymidine kinase (rhTK) and characterized by Western immunoblotting, enzyme-linked immunosorbent assay (ELISA) and immunostaining of tumor cells. Twenty-three clones of TK mAbs were characterized to recognize specifically not only rhTK produced by Escherichia coli but also TK subunit of 25 kDa in human lung cancer. The anti-TK mAbs reacted specifically with cytosolic TK but not with mitochondrial TK. Only one clone of the mAbs inhibited the catalytic activity of TK. By solid phase sandwich enzyme immunoassay using these mAbs, we could quantitate the cytosolic TK content in tissues. Immunohistochemical staining analysis using one of the TK mAbs showed that human lung adenocarcinoma and squamous cell carcinoma exhibited much higher staining intensity than stromal cells. These mAbs are useful for biochemical studies on the regulation of human TK in proliferating cells such as tumor cells and for diagnosis of highly proliferating tumors.