Search

Background: One characteristic of Lynch syndrome, which is caused by germline mutations in a group of genes encoding mismatch repair proteins, is the early onset of colorectal cancer. Here, we report a rare case of juvenile colon cancer, diagnosed based on the onset of intussusception with high microsatellite instability (MSI) and the absence of BRAF mutations, which was suggestive of Lynch syndrome. Case presentation: A 28-year-oldman presented with right lower abdominal pain for approximately 3 months and defecated blacky stool for several weeks. He visited our hospital because of increasingly intense right lower abdominal pain. Computed tomography revealed a contrast-enhanced tumor and lymph nodes with a crab-claw-like fitted image extending into the ascending colon. Colon endoscopy revealed a large submucosal tumor-like lesion with ulceration. Laparoscopy-assisted ileal resection with level 3 lymph node dissection was performed 3 days after the endoscopic reduction of the intussusception. The histological diagnosis was a poorly differentiated adenocarcinoma. Gene analysis of the resected tumor revealed high MSIand KRAS mutations, and the absence of BRAF mutations. Immunohistochemistry indicated the absence of MLH1 and PMS2 expression in tumors. Genetic analysis of peripheral blood and tumors revealed no pathological mutations in MLH1, MSH2, PMS2, or MSH6. Conclusion A rare case of Lynch-like syndrome was diagnosed with intussusception. MSI-high, wild-type BRAF, and the absence of MLH1 and PMS2 expression suggested Lynch syndrome. The absence of pathological mutations in germline and somatic genes suggests the possibility of MLH1 promoter methylation or MLH1 epimutation in the pathogenesis of this case.

Introduction Combined treatment using anti-programmed death-ligand 1 antibody (anti-PD-L1) and platinum-etoposide is the current standard first-line treatment for patients with extensive-stage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ES-SCLC after the first-line treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ES-SCLC, and treatment with irinotecan is well established as both, a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the second- or later-line setting for patients with ES-SCLC who are previously treated with a combination of anti-PD-L1 and platinum-etoposide. Methods Our study will enroll patients who are diagnosed with ES-SCLC and experienced disease progression after treatment of anti-PD-L1 and platinum-etoposide. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4 weeks. Doses of irinotecan (100/80/60 mg/m2) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator’s decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progression-free survival, and safety. Discussion Since the present first-line treatment has been changed to combined treatment with anti-PD-L1 and platinum-etoposide, the second- or later-line treatment should be re-evaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This IRICO study demonstrates and re-evaluates the clinical benefits of irinotecan after combined treatment with anti-PD-L1 and platinum-etoposide for patients with ES-SCLC. Registration details This study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021.

We first measured 4- and 5-photon annihilations in positronium using a multiphoton spectrometer (UNI), which consists of 32 NaI(Tl) scintillators with lead shields, each being located on a surface of an icosidodecahedron. The front face of each scintillator is placed at a distance of L = 262 mm from the center of the UNI. With this setup, the detection efficiency of 4- and 5-photon-annihilation processes are too small to get a sufficient number of events to analyze the physics. To obtain a larger detection efficiency, we must set the NaI(Tl) scintillators closer to the target. The original principle in designing the UNI was to suppress backgrounds (BG) and make them as low as possible allowing modest efficiencies for 4- and 5-photon-annihilation events, i.e., to get the highest signal-to-noise ratio (S/N). The new concept is to get the highest S/σ where σ is an error of one standard deviation of the signal including BG effects. A higher S/σ means a larger number of events with smaller BG taking into account a statistical effect. The detection efficiencies with BG effects are studied with respect to L using a detector simulator based on the EGS4 code in which 2- to 5-photon-annihilation events are generated by quantum-electrodynamic processes based on GRACE and BASES/SPRING codes. As a result, the detection efficiency and S/σ of 5-photon annihilations at L = 136 mm are 529 and 17 times larger than those at L = 262 mm, respectively. PACS Nos.: 36.10Dr, 12.20Fv, 13.10+q

We focused on the presence of water absorbed in the grain boundary of a polycrystalline transition metal oxide (TMO) film in an EL/poly-TMO/EL structure. The effect of supplying water to resistive random access memories (ReRAMs) of Pt/NiO/Pt structure on switching voltages and data retention characteristics was investigated. As a result, switching voltages were decreased by supplying water and reset switching was confirmed to be strongly induced by supplying water even at room temperature without applying voltage. These results suggest that water enhances resistive switching effect by providing reducing species and oxidizing species respectively such as H+ and OH-.

Effects of day and night temperatures on the growth and the tuber formation of Sandersonia aurantiaca plants were investigated. Seedlings with 1 or 2 leaves were transferred to growth chambers, controlled at day/night temperatures of 17/12°C, 24/17°C, and 30/24°C under natural daylength. On plants kept at 30/24°C, the unfolding of leaves, stem elongation, and the branching from the main stem were enhanced, whereas those at 17/12°C were retarded. At 24/17°C, intermediate vegetative growth and optimum growth for flower stalk elongation and flowering were educed. At the time of shoot die back, the fresh and dry weights of new tubers were greatest at 24/17°C, moderate at 30/24°C, and smallest at 17/12°C. At 17/12°C and 24/17°C, normal fingerlike or fork shaped tubers developed, while at 30/24°C, secondary tubers formed and developed. These results indicate that 24/17°C is optimum for tuber and flower development of sandersonia plants.

Positronium (Ps) is a bound state of an electron and a positron, which annihilates into photons. It is a suitable place to study the quantum electrodynamics (QED) since strong and weak interactions are negligibly small in the annihilation processes. Our experimental group has been measuring rare annihilation processes from Ps using a multi-γ-ray spectrometer called UNI which consists of 32 NaI(Tl) (3 in. φ ×4 in.) scintillation counters. We had detected the 4γ and 5γ annihilation processes for the first time in the world. In the experiment, ∼200 4-γ events and one 5-γ event have been collected, respectively, until today. Since these processes do not include any lower order of Feynman graphs, we can study α 7 and α 8 ( α : fine structure constant) processes almost purely, which is unexplored region of the QED higher order processes. We are planning to utilize a positron beam line using permanent magnets. By employing EGS4 code system for simulating electromagnetic processes and Runge–Kutta method for solving equations of motion, detection efficiency of our detector and transport efficiency of the beam line have been simulated.

How different day/night temperature affect the growth and development of the vegetative and reproductive parts, including the bulbs of amaryllis (Hippeastrum hybridum) plants in growth chambers for two years was investigated. One-year-old, 2-leafed seedlings were transferred to growth chambers set at 17 °/12°C (low, L plot), 24°/17°C (middle, M plot) and 30/24°C (high, H plot) under natural daylength.1. High temperatures (H plot) hastened the unfolding and elongation of leaves, and increased markedly the growth of mother bulb and daughter bulbs, but the plants did not flower.2. In plants exposed to low temperature (L plot), the leaves were the slowest of the three plots to unfold and elongate; the mother bulbs were slow to enlarge but produced the most daughter bulbs. The temperature favored floral development.3. Middle temperature (M plot) educed intermediate vegetative growth and the enlargement of mother and daughter bulbs. This condition was optimum for flower stalk elongation and flowering.Thus, comparing the responses of amaryllis grown under low, middle, and high day/night temperatures, high temperature favored promotion of mother bulb enlargement, but the moderate and low temperatures were optimum for bulb and flower production.

To make clear factors of flowering in Chinese yam (Dioscarea opposita Thunb.), effects of seed tuber size and seed tuber removal on flowering were determined. Growth patterns of plants with or without flowering were analyzed.1. Plants of D. opposita Thunb. 'Ichoimo' planted in late May, 1994, initiated flower bud from late June to early July.2. Minimum fresh seed tuber weights for flowering were 40 g in 'Ichoimo' and 75 g for 'Nagaimo' in 1993; their dry weights were 10.8 and 9.8 g, respectively. Flowering occurred on plants started from seed tubers which weighed 10 g or more in dry weight.3. When seed tubers were excised early from the mother plants, the number of flowering plants decreased significantly. Conversely, when the seed tubers were removed later, an increased frequency of flowering plants was observed.4. Although there were no differences in the lengths of the main stem, dry weights of roots and new tuber between plants with and without flowers, total length of lateral branches on flowering plants was longer than that of plants without flowers.

The effects of brassinosteroid on growth parameters of two day-neutral strawberries (Fragaria × ananassa Duch. 'Miyoshi' and 'Enrai') grown in a greenhouse were investigated. In both cultivars, brassinosteroid increased total leaf areas by 150-180% and the number of leaves, petiole length, and number of crowns by 110-140% over the untreated control plants. Runner formation was unaffected by the brassinosteroid. Dry weights of leaves, petioles, crowns, and total organs of plants treated with brassinosteroid were heavier than those of untreated plants, whereas the dry weights of roots from treated plants were equally heavy as those of the control. Brassinosteroid significantly increased the total number of flowers and number of inflorescences per plant, but not the number of flowers per inflorescence. Brassinosteroid significantly increased total marketable berries and total yield per plant in 'Miyoshi', but it did not increase yields of 'Enrai'.

Treatment with 300 μM cycloheximide (CHI), an inhibitor of protein synthesis, decreased length, fresh and dry weights, total soluble sugar (TSS), and protein contents ofperianths on cut spikes of 'Fujinoyuki' gladiolus. The treated florets remained folded.CHI did not affect acid invertase activity but it inhibited protein synthesis other thanacid invertase while lowering TSS contents in the perianths.CHI treatments of excised, fully open florets prevented fresh and dry weight losses, and the reduction of TSS and protein in the perianths.CHI also inhibited an increase ofthe ion leakage from perianth tissues and delayed the onset of wilting. Relationship between CHI and changes in these parameters are discussed.

Viable mesophyll protoplasts were isolated from in vitro grown leaves of grapes (Vitis labruscana cv. Kyoho and V. vinifera cv. Cabernet Sauvignon). The best yield of mesophyll protoplasts (1.8 × 107 and 2.4 × 107 • g -1 leaf fresh weight, 'Kyoho' and 'Cabernet Sauvignon', respectively) was obtained in a combined enzyme solution of 0.5% Cellulase YC, 0.2% Macerozyme R -10 and 0.1% Driselase. More than 85% of the isolated protoplasts were viable. Most protoplasts regenerated the cell wall within first 5 days of culture. Cell division occurred after 5 to 10 days of culture in Gamborg's B5 liquid medium supplemented with 5μM 2, 4 - D, 2.5μM BA and 0.6 M sorbitol. In 'Kyoho', 12% of cell division frequency was found in the protoplasts isolated with 0.5% Cellulase YC, 0.2% Macerozyme R -10, 0.1% Driselase and 0.01% Pectolyase Y -23. In 'Cabernet Sauvignon', the frequency of cell division was low (1.4%) when the same enzyme solution was used for the protoplast isolation.

Export of soluble sugar, changes in all membrane permeability, and production rate of ethylene in the perianths of the lower florets on the gladiolus spikes were determined as related to physiological events affecting the wilting of perianths after they were fully unfolded.1. Perianths appeared to be wilting between 2 and 3 days after unfolding fully (DAU). Concurrent with the onset of wilting, perianths rapidly decreased in fresh and dry weights.2. Between 1 and 2 DAU, one day before perianths started to wilt, total soluble sugar contents began to decrease. Between 2 and 3 DAU, the largest loss of total soluble sugars occurred, most of which was possibly due to export from perianths to other parts.Concurrent with the export of sugars, an increase in leakage of ions from perianth tissues was observed.3. Rates in ethylene production of perianths did not show a significant change in relation to the time of wilting.Depletion of sugars was discussed as related to the disintegration of membranes, which could cause perianths to wilt.

In this study, the effects of root temperatures on flower formation and fruit yield of tomato plants were investigated.1. Roots of young tomato seedlings were bathed in containers of nutrient solution kept at temperatures ranging from 10°to 35°C at 5°C intervals. The experiments ran from 14 to 21 days beginning at cotyledon expansion. Shoot and root growths of seedlings kept at root temperatures 25°and 30°C were greater than those of seedlings grown at other root temperatures. The number of flowers on the first truss of plants whose roots were exposed to 25°C was greater than those on trusses of seedlings grown at other root temperatures, whether the air temperature remained constant at 20°or fluctuated between 20°and 30°C. No difference in the number of nodes on the primary axes among plants was found in this experiment.2. In experiments conducted during three different times of the year; spring, late spring to early summer, and late fall to early winter, roots of plants were exposed to various temperatures from anthesis of flowers on the first truss to fruit harvest on the third truss. Shoot growth of plants grown at root temperatures between 20°and 30°C was better than that of plants grown at other root temperatures. Root temperatures favorable for root growth have a range lower than that for optimum shoot growth. Fruit production from plants grown at root temperatures of 10°and 35°C was very low because of poor fruit set and growth, especially on those of second and third trusses.3. Fruit ripening was accelerated on plants grown at root temperature of 10°and 15°C, especially in the 15°C treatment if the nutrient solution was low in nitrogen.4. These results confirm that the optimum range of root temperatures for the growth of tomato vines widens with increasing size and age of plants from the young seedling stage to mature producing vines, that is 25°30°C during the flower differentiation period in the first truss, 20°30°C for the vegetative growth stage, and 15°30°C during fruit production.

This study was conducted to clarify the rooting ability of 6 willow species, and the relationship between seasonal changes in the rooting ability of cuttings and the content of endogenous factors in comparison of easy- and difficult-to-root willows.Among easy-to-root willows there were Salix koriyanagi, S. gilgiana, S. babylonica and S. alba, and among difficult-to-root willows there were S. bakko and S. vulpina. Cuttings of S. koriyanagi, an easy-to-root willow, rooted readily throughout the year irrespective of NAA treatment. Cuttings of S. bakko, a difficult-to-root one, rooted poorly without NAA treatment. With NAA treatment, however, they rooted well from July to October, but did poorly thereafter.No differences in the activity of extracted auxin, nor in the content of total phenols were found between the easy- and difficult-to-root willows. The root promoting activity of water extract was always higher in the easy- than difficult-to-root willows, but it did not seem to participate in the seasonal changes in rooting ability in both the easy- and difficult-to-root willows, because of the lack of the correlation between them. In S. koriyanagi with and without NAA treatment and S. bakko without NAA treatment, there were no significant correlations between seasonal changes in the rooting ability and in the activity or content of endogenous factors. Only in S. bakko with NAA treatment, however, a significant correlation was recognized between the rooting ability and the activity of extracted auxin.

The effect of light on anthocyanin production in apple (Malus pumila Mill. cv. Jonathan) skin disks was investigated, with prolonged irradiation from different light sources. High fluence rates of white light provided from a xenon lamp were unable to produce large amounts of anthocyanin, and anthocyanin production became saturated at about 30 W m−2. When UV-B light, provided by a fluorescent lamp which had an emission peak at 312 nm, was combined with the white light, anthocyanin production was synergistically stimulated and increased up to the highest fluence rates of white light tested (44 W m−2). This UV-B light was more effective than red and blue light provided from fluorescent lamps, but anthocyanin production became saturated at about 1.7 W m−2. However, simultaneous irradiation with red and UV-B light had a synergistic effect. UV-B light was also effective in increasing anthocyanin production in whole fruit. Therefore this synergism seemed to have an important role in the development of the desirable red skin color under field light conditions. The results of aminoethoxyvinylglycine treatment suggested that ethylene was not involved in the stimulative effect of UV-B light.

To elucidate the characteristics of color development in apple cvs ‘Starking Delicious’ (‘SD’), ‘Fuji’ and‘ Mutsu’, the effeccts of light on anthocyanin synthesis and L-phenylalanine ammonia-lyase (PAL) activity were investigated. Irradiation with white light and simultaneous irradiation with white and ultraviolet light with an emission peak at 312nm (white+UV 312) were used. When the whole fruit skin was examined, ‘SD’ produced higher anthocyanin levels than ‘Fuji’especially under white light. In skin disks, however, anthocyanin synthesis was increased in ‘Fuji’to the same level as in ‘SD’. The yellow-colored cultivar, ‘Mutsu’, did not respond to white light, and only produced a small amount of anthocyanin under white+UV 312 light. In whole fruit skin at least, there was a close correlation between anthocyanin synthesis and PAL activity. In skin disks, PAL activity was far higher than in whole fruit skin, however, anthocyanin synthesis did not show a similar increase in PAL activity. In ‘Mutsu’, white light did not induce anthocyanin synthesis although it stimulated PAL activity to the same extent as the white+ UV 312 light.

The investigations on manganese deficiency and its control were carried out from 1955 to 1957 on different kinds of citrus growing in Kanagawa Prefecture.The manganese deficiency symtoms were clear in June when the spring-flush leaves had reached the full size. The interveinal tissues of the leaves turned yellow, leaving a band of green tissues on both sides of the main veins and the mid rib. The contrast in the color of the main veins and adjacent tissues with the interveinal chlorotic portion was not so clear as in zinc deficient leaves. Such leaves were observed throughout the tree, irrespective of the directions in which the orchards were sloping.The severity of manganese deficiency seems to vary from variety to variety, i.e., Naruto (C. medioglobosa Hort.) and Natsudaidai (C. natsudaidai HAYATA) showed the severest symptoms, Unshiu (C. unshiu MARCOV.) showed them moderately, while early Unshiu and sweet oranges were slightly affected.Manganese content in spring-flush leaves increased till August, and thereafter remained fairly constant. Leaf analyses were done in order to find out the manganese content of leaves in 150 Unshiu orchards located in Kanagawa Prefecture. Close relationship between the severity of deficiency symptoms and the manganese content of leaves was recorded. All orchards with leaf manganese less than 15ppm on dry weight basis showed the deficiency symptoms, and 77 per cent of the orchards with leaf manganese less than 20ppm also showed these symptoms.Manganese content in citrus leaves of Kanagawa Prefecture were comparatively lower than those of the other districts, i.e., 71 per cent or more of the orchards in this Prefecture had manganese content lower than 25ppm on dry wight basis. Manganese deficiency symptoms were found in 67 per cent orchards on volcanic ash soils, where average leaf manganese content was 16.01ppm; in 27.3 per cent of the orchards on volcanic gravelly sandy soils the average leaf manganese content was 20.91ppm; and in 36.8 per cent of the orchards on gravelly clay soils it was 21.5ppm.Contents of different elements in leaves collected from 100 orchards in 1956 ranged as follows; nitrogen, 2.88-4.14 per cent; phosphorus, 0.14-0.24 per cent; potassium, 0.762-44 per cent; iron, 95-375ppm. A positive correlation was noted between manganese and phosphorus contents in the leaves and it was statistically significant at 1 per cent level.To contral manganese deficiency, one or two sprayings of 0.4 per cent solution of manganese sulfate before the leaves of spring-flush reached the full size were found effective. Mixture of lime and the above solution appears to be less effective in controlling the manganese deficiency.The soil applications of manganese fertilizers showed no favourable effect on the plants. Foliar applications of manganese to the deficient trees increased manganese content in young spring flush leaves sampled a year after spraying as compared with leaves of the same age from unsprayed trees.