Use of a high-throughput umu-microplate test system for rapid detection of genotoxicity produced by mutagenic carcinogens and airborne particulate matter

In the present study, we developed a rapid umu-microplate test system that uses the nitroreductase- and O-acetyltransferase-overproducing Salmonella typhimurium strain NM3009 and the O-acetyltransferase-overproducing S. typhimurium strain NM2009 to detect genotoxic activity in small volume samples. The assay was used to test the genotoxicity of several standard mutagens and environmental samples. Exponentially growing cultures of NM3009, NM2009, and the parental strain TA1535/pSK1002 were incubated in 96-well microplates with test chemicals both in the presence and in the absence of rat liver S9. The relative beta-galactosidase activities were then determined colorimetrically using either chlorophenol red-beta-D-galactopyranoside (CPRG) or O-nitrophenyl-beta-D-galactopyranoside (ONPG) as a measure of umuC gene induction activity. The sensitivities of NM3009 without S9 mix and NM2009 with S9 mix to nitroarenes and aromatic amines were up to 24- to 75-fold higher than those of the parent strain. Induction of umuC gene expression was detected more readily with CPRG than ONPG. The umu-microplate assay also detected genotoxicity in organic extracts of particulate matter from air samples collected in Osaka City, Japan. The pattern of the responses suggested that the genotoxic activity of the particulate extract was due primarily to nitrated polycyclic aromatic hydrocarbons. Our results indicate that the umu-microplate assay may be a useful way of carrying out rapid screens for genotoxicity in small-volume environmental samples.     

Mediastinal lymph node metastasis of colon cancer: Report of a case

We herein describe a patient with mediastinal lymph node metastases which occurred after both a primary sigmoid colon cancer and metachronous ovarian metastasis had been resected. The most likely route of metastases to the mediastinum in this case is the paravertebral venous plexus probably connected to the ovarian metastasis, or so-called remetastasis. This case illustrates that the mediastinum is thus a possible metastatic site in patients with colon cancer. Surgeons should therefore pay attention to the mediastinum as well as the lung fields when checking chest X-ray films during a follow-up of patients after a resection of colon cancer.     

The fertilizing ability of human epididymal sperm

Purpose: Membrane cofactor protein (MCP), CD46, whose primary function is to protect host cells from homologous complement, has been presumed to serve as a sperm adhesion molecule for oocytes. The purpose of this study was to clarify the relationship between the properties of MCP expressed on epididymal sperm and their fertilizing ability in a recently developed strategy for assisted reproduction. Methods: We collected ejaculated sperm from normal subjects and epididymal sperm from vasectomized subjects and patients with congenital absence of the vas deferens. Western blotting and cofactor activity assay were performed to investigated the structural and functional properties of MCP. Results: Epididymal spermatozoa which showed a reduced fertilizing ability tended to react poorly with antibodies against MCP and also showed low cofactor activity, indicating weak complement regulatory activity compared to that of ejaculated spermatozoa. Conclusions: MCP is sufficiently expressed in ejaculated sperm in men with a normally developed epididymis but is diminished in epididymal sperm from men with congenital or acquired obstruction of the vas deferens.     

Circadian Changes in Urine Volume and Frequency In Elderly Men

Purpose

Circadian changes in urinary frequency, diuresis and bladder capacity were evaluated in middle-aged and elderly patients.

Materials and Methods

A total of 2,703 urinations from 50 men (median age 66 years) was recorded with a 24-hour uroflowmetry system.

Results

During a 24-hour period the elderly group showed increased frequency and decreased bladder capacity. No difference was observed in diuresis between the 2 age groups. From midnight to 6 a.m. frequency in the elderly group was significantly greater (p less than 0.01) than that in the middle-aged group.

Conclusions

Increased frequency in the elderly group during these hours was primarily due to an increase in diuresis.     

Quality of life (QOL) and nutrition

We thought that nutritional parameters in laboratory data might be able to express quality of life (QOL). Therefore, in 70 patients with malignant chest diseases (NSCLC, 42 patients; SCLC, 15; lung metastasis, 7; others, 6), the correlation between nutritional parameters of total protein (Tp), serum albumin (Alb), and serum (cholinesterase (ChE] and Karnofsky Performance Status scale (KPS) was investigated. Then, in 24 patients with them (NSCLC, 12; SCLC, 6; lung metastasis, 4; others 2), Alb and ChE were compared to the EORTC Core Quality of Life Questionnaire and Lung Cancer-Specific Questionnaire Module (QS). Results were as follows: 1) KPS and nutritional parameters correlated (Tp. r = 0.55, p less than 0.001; Alb, r = 0.60, p less than 0.001, ChE, r = 0.60; p less than 0.001). 2) The cores for Functional Status (FS) and Disease and Treatment-related symptoms (Sym) in QS and parameters of Alb and ChE correlate (FS v.s. Alb, p less than 0.01; Sym v.s. Alb, p less than 0.01; FS v.s. ChE, p less than 0.05; and Sym v.s. ChE, p less than 0.05). Moreover, the scores of Psychological Distress in QS and Alb showed a correlation (p less than 0.05). It is considered that nutrition and part of QOL (KPS and FS + Sym in QS, that is to say, "objective" functional activity and "subjective" functional activity and symptoms) correlate, and that nutritional parameters are useful to evaluate QOL.     

Long-lasting renal dysfunction following tacrolimus induction therapy in ulcerative colitis patients

Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of −34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (β = −0.3242, p = 0.0103) and peak serum trough level during TAC treatment (β = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation.     

Case of follicular mucinosis showing brownish yellow and red dots via dermoscopy

We herein describe a 68‐year‐old man with follicular mucinosis. A dermoscopic examination showed multiple, round, brownish yellow dots with a whitish rim in the follicular ostium and red dots in the interfollicular area. This case report is the first to suggest that follicular mucinosis shows these dermoscopic findings.     

Effectiveness of a new triple-row circular stapler in reducing the risk of colorectal anastomotic leakage: A historical control and propensity score–matched study

Anastomotic leakage (AL) after colorectal surgery is a serious complication. This study aimed to evaluate the effectiveness of the EEA™ circular stapler, a new triple-row circular stapler (TCS), relative to a conventional, double-row circular stapler (DCS).A total of 285 patients who underwent anastomosis with the double stapling technique at the Tokyo Medical University Hospital between 2017 and 2021 were included in this nonrandomized clinical trial with historical controls using a propensity score (PS) analysis. The primary endpoint was the risk of AL.We performed a 1:2 PS matching analysis. Before case matching, AL occurred in 15 (7.4%) and 2 (2.4%) patients in the DCS and TCS groups, respectively, with no significant difference (P = .17). After case matching, AL occurred in 13 patients (11.6%) and 1 patient (1.8%) in the DCS and TCS groups, respectively, revealing a significant difference (P = .04). Cox models were created by applying PS to adjust for group differences via regression adjustment. Odds ratios for AL in the DCS group versus the TCS group were 0.31 (95% confidence interval [CI]: 0.07–1.38) in the entire cohort, 0.15 (95% CI: 0.02–0.64) in the regression adjustment cohort, and 0.14 (95% CI: 0.02–1.09) in the 1:2 PS-matched cohort.PS analysis of clinical data suggested that the use of TCS contributes to a reduced risk of AL after colorectal anastomosis CTwith the double stapling technique.     

Dosimetric effect of set-up error in accelerator-based boron neutron capture therapy for head and neck cancer

The dosimetric effect of set-up error in boron neutron capture therapy (BNCT) for head and neck cancer remains unclear. In this study, we analyzed the tendency of dose error by treatment location when simulating the set-up error of patients. We also determined the tolerance level of the set-up error in BNCT for head and neck cancer. As a method, the distal direction was shifted with an interval of 2.5 mm, from 0.0 mm to +20.0 mm and compared with the dose at the reference position. Similarly, the horizontal direction and vertical direction were shifted, with an interval of 5.0 mm, from −20.0 mm to +20.0 mm. In addition, cases with 3.0 mm and 5.0 mm simultaneous shifts in all directions were analyzed as the worst-case scenario. The dose metrics of the minimum dose of the tumor and the maximum dose of the mucosa were evaluated. From unidirectional set-up error analysis, in most cases, the set-up errors with dose errors within ±5% were Δdistal < +2.5 mm, Δhorizontal < ±5.0 mm and Δvertical < ±5.0 mm. In the simulation of 3.0 mm shifts in all directions, the errors in the minimum tumor dose and maximum mucosal dose were −3.6% ±1.4% (range, −5.4% to −0.6%) and 2% ±1.4% (range, 0.4% to 4.5%), respectively. From these results, if the set-up error was within ±3.0 mm in each direction, the dose errors of the tumor and mucosa could be suppressed within approximately ±5%, which is suggested as a tolerance level.     

Determining a methodology of dosimetric quality assurance for commercially available accelerator-based boron neutron capture therapy system

The irradiation field of boron neutron capture therapy (BNCT) consists of multiple dose components including thermal, epithermal and fast neutron, and gamma. The objective of this work was to establish a methodology of dosimetric quality assurance (QA), using the most standard and reliable measurement methods, and to determine tolerance level for each QA measurement for a commercially available accelerator-based BNCT system. In order to establish a system of dosimetric QA suitable for BNCT, the following steps were taken. First, standard measurement points based on tissue-administered doses in BNCT for brain tumors were defined, and clinical tolerances of dosimetric QA measurements were derived from the contribution to total tissue relative biological effectiveness factor-weighted dose for each dose component. Next, a QA program was proposed based on TG-142 and TG-198, and confirmed that it could be assessed whether constancy of each dose component was assured within the limits of tolerances or not by measurements of the proposed QA program. Finally, the validity of the BNCT QA program as an evaluation system was confirmed in a demonstration experiment for long-term measurement over 1 year. These results offer an easy, reliable QA method that is clinically applicable with dosimetric validity for the mixed irradiation field of accelerator-based BNCT.