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During the 2020–2021 winter season, we detected 6 gamma‐ray glows at Kanazawa University, Japan. Negative surface electric fields (E‐fields; in the sign convention of atmospheric electricity) were observed by a field mill during all the glow cases. In five of the six cases, the peak E‐field reached around −12 kV m−1, and the E‐field during the glow detection was the strongest in the interval including 3 hr before and after the detection time. Therefore, negative charges should have been dominant in the thunderclouds that produced the gamma‐ray glows, and electrons were probably accelerated and multiplied by the E‐fields between a predominantly negative charge layer and a localized positive charge layer below. In addition, we extracted 8 non‐detection cases in the 2020–2021 winter season, in which surface E‐fields were stronger than −12 kV m−1. In 5 of the 8 cases, radar echoes were inadequately developed, suggesting insufficient charge accumulation. On the other hand, the remaining 3 cases had well‐developed radar echoes, and there was no significant difference from the detection cases. Plain Language Summary: Gamma‐ray glow is a minute‐lasting burst of high‐energy photons associated with thunderclouds. High‐energy photons are considered to originate from high‐energy electrons accelerated and multiplied in strong electric fields inside thunderclouds. When a gamma‐ray glow is detected on the ground, electrons are considered to be accelerated downward by upward electric fields. In the 2020–2021 winter season, we detected a total of 6 gamma‐ray glows during winter thunderstorms at Kanazawa University, Japan. An electric‐field monitor recorded negative electric fields at the surface during all the glow detections, indicating negative charges overhead. It suggests that the thunderclouds that produced the gamma‐ray glows were strongly charged negatively, and a localized positive charge layer existed in the lower part to produce an upward electric field for downward electron acceleration. Key Points: In the 2020–2021 winter season, 6 gamma‐ray glows were detected at Kanazawa University, Japan, with electric‐field measurementSurface electric fields were negative during the detection of all the gamma‐ray glowsHigh‐energy electrons seemed to be produced between a well‐developed negative charge region and a localized positive charge region below [ABSTRACT FROM AUTHOR]

Relativistic Runaway Electrons Avalanches (RREAs) development depends on the applied electric field and the environment's air density. This dependency controls the RREA exponential growth length scale. The RREA development affects the bremsstrahlung excess occurring due to the passage of charged particles through the thundercloud's electric fields, the gamma‐ray glow. We used Monte Carlo simulations to develop an empirical model showing the RREA behavior in a realistic atmospheric density profile. The new formulation shows how the density variation modulates the electron population under electric field strengths near the RREA electric field threshold. The model limits the initial RREA altitude range as a function of the electric field strength. The new model is valid between ∼0.6 and ∼18 km, covering the relevant heights to investigate the generation of ground‐detected gamma‐ray glows. Plain Language Summary: Thunderclouds are energy sources for trespassing charged particles from cosmic rays. This extra energy gain may induce electron avalanches, known as Relativistic Runaway Electron Avalanches (RREAs), resulting in an enhanced gamma‐ray flux via bremsstrahlung, the gamma‐ray glow. Recent studies relate this enhancement to electric field strengths close to the RREA requirement. The atmospheric density variations affect avalanche development by modifying the RREA requirement, resulting in isolated avalanches by imposing limits to the avalanche's initial altitude. We show how RREAs develop in a realistic atmospheric density profile. We present a modification on the characteristic avalanche length under this condition. The initial avalanche altitude is crucial because it completely modifies the density profile trespassed by a downward electron shower. Finally, we discuss the consequences of isolated RREAs for high‐energy emissions and show that the electric field strength constrains the possible initial altitudes for the gamma‐ray glow. Key Points: A new empirical model quantifies how electron avalanches vanish because of atmospheric density variations with ∼10% accuracyThe model limits the initial altitude of electron avalanche development for electric field strengths near the avalanche thresholdWe narrow the possible gamma‐ray glow source height range with the new model which is valid through ∼0.6–18 km [ABSTRACT FROM AUTHOR]

A gamma‐ray glow, a minute‐lasting burst of high‐energy photons from a thundercloud, was detected by ground‐based apparatus at Kanazawa University, Japan, in a winter thunderstorm on 18 December 2018. The gamma‐ray glow was quenched by a lightning flash within a brief time window of 40 ms. The lightning flash produced several low‐frequency (LF) E‐change pulses that were temporally coincident with the termination of the gamma‐ray glow, and that were located within 0.5 km from the observation site by the Fast Antenna Lightning Mapping Array. The LF pulses had the same polarity as a positive cloud‐to‐ground current and a normal‐polarity in‐cloud current. Since this polarity is against the upward electric field for producing the gamma‐ray glow (accelerating electrons to the ground), we infer that the glow was terminated by a normal‐polarity in‐cloud discharge activity between a middle negative layer and an upper positive layer. Plain Language Summary: Strong electric fields inside thunderclouds may accelerate electrons to relativistic energy, and cause a burst of high‐energy photons called gamma‐ray glow. Gamma‐ray glows are sometimes terminated with a lightning flash as it discharges electric fields responsible for electron acceleration. In this study, we observed the termination of a gamma‐ray glow with a detailed lightning mapping observation in the radio‐frequency band. An in‐cloud lightning flash between two charge layers inside a thundercloud reduced an electric field that accelerated electrons. Radio‐frequency observations of glow termination are a powerful tool to investigate the charge structure associated with electron acceleration. Key Points: A gamma‐ray glow was terminated by a lightning flash within a brief time window of 40 msPositive‐polarity low‐frequency pulses were located within 0.5 km of the detection siteThe glow was ceased by a normal‐polarity in‐cloud discharge activity between a middle negative layer and an upper positive layer [ABSTRACT FROM AUTHOR]

Electric field of thunderclouds modifies components and energy spectra of the cosmic‐ray air shower. In particular, thunderstorms accelerate charged particles, resulting in an enhancement of gamma‐ray fluxes on the ground, known as a gamma‐ray glow. This phenomenon has been observed in recent years by the Gamma‐Ray Observation of Winter THunderclouds collaboration from winter thunderstorms in the Hokuriku area of Japan. The present work examines the ambient conditions required to produce spectral features of the previously detected gamma‐ray glows, by using Monte Carlo simulations of particle interactions in the atmosphere. We focus on three parameters, the strength and length of the electric field, and the length of a null‐field attenuation region below the electrified region. The average spectrum of observed gamma‐ray glows in winter thunderstorms of Japan requires an electric field intensity close to 0.31 MV/m, slightly exceeding the Relativistic Runaway Electron Avalanche threshold of 0.284 MV/m. The vertical size of the electric field region should be comparable to 1 km. The estimated attenuation region size is 300–500 m, necessary to reduce the low‐energy photon flux of the average gamma‐ray glows. There is still a wide range of acceptable parameter sets with degeneracy to make a similar spectrum. Plain Language Summary: Thunderclouds modify the incident cosmic‐ray flux due to their electric field. In particular, thunderstorms accelerate charged particles inducing enhancement of the gamma‐ray flux at the ground, known as the gamma‐ray glow. Throughout recent years, the community observes gamma‐ray glows on the Japanese Hokuriku coast. This paper examines the ambient conditions required to produce the characteristic gamma‐ray glow spectrum using Monte Carlo simulation. We focus on the electric field strength, and electric field length and introduced a null‐field attenuation region following previously reported features of Japanese winter thunderclouds. We conclude that most observed gamma‐ray glows at the Hokuriku region require electric fields close to 0.32 MV/m along approximately 1 km and an attenuation region of 300–500 m to reproduce the observations. Finally, the three studied variables can be differently combined to generate similar spectra regarding a space of phase of three coordinates being electric field strength, electric field length, and attenuation space length. Key Points: We use Monte Carlo simulations of electron and gamma‐ray interactions in thunderstorms to explain observed gamma‐ray glowsWe successfully simulated gamma‐ray glow spectra and extracted an acceptable set of ambient atmospheric factors of the glowFit configurations have electric fields as ∼0.30 MV/m with a ∼1 km size scale and a null field region of ∼0.5 km below that [ABSTRACT FROM AUTHOR]

Gamma‐ray glows associated with thunderclouds have been observed since the 1980s, however it remains unclear how, and at which thunderstorms gamma‐ray glows are generated in dense atmospheres. In this study, we report the first Compton camera imaging of a gamma‐ray glow from a winter thundercloud. On 14 January 2022, using two identical Bi4Ge3O12 scintillators in energy range of 0.05–5 MeV, we detected two gamma‐ray glows lasting ∼4 min in a mountain area 25 km from the Japan Sea and 410 m above sea level. The same events were also observed by the Compton camera, where the first glow we observed suggested statistically significant (4.0 and 5.9 σ level) signals of two enhanced concentrations in gamma‐ray photon images in a range of 0.15–1.5 MeV. These concentrations were most clearly observed in a time window of Δt = 50 s around the peak intensity of the gamma‐ray glow. Plain Language Summary: Observations of gamma rays from thunderclouds started in 1980s, leading to intensive studies in the last 40 years. However, the question of where and how such gamma rays are produced in thunderclouds remains unclear, as no gamma‐ray images have been obtained to date. This paper presents the first successful gamma‐ray imaging of a thundercloud in a winter of Japan. In particular, we installed a Compton camera of 10 × 10 cm2 in size, that is a compact but high sensitivity camera originally developed in the field of astronomy to observe gamma‐ray sky. At the peak of a gamma‐ray emission, we detected significant enhancements in the gamma‐ray photon image. The image provides the source position and beam pattern of the gamma‐ray emission, thus may be connected to highly electrified region and electron acceleration inside thunderclouds. Key Points: Gamma‐ray glows were observed in a mountainous area 25 km from the Japan Sea and 410 m above sea level on 14 January 2022, during winterOne of the glows suggested two enhanced concentrations in gamma‐ray images, which was taken for the first time with a Compton cameraThe first successful gamma‐ray imaging provides a new means of investigating radiation beam pattern of gamma‐ray glows in thunderclouds [ABSTRACT FROM AUTHOR]

Winter thunderstorms in Japan have been recognized as an ideal target to observe high‐energy atmospheric phenomena thanks to low‐charge‐center cloud structures. During four winter seasons in Japan (from 2016 October to 2020 March), seven downward terrestrial gamma‐ray flashes (TGFs) were detected by gamma‐ray and broadband low‐frequency (LF: 0.8–500 kHz) monitors. All the detected TGFs took place at the initial stage of lightning flashes. Based on the LF observation, the seven downward TGFs in the present study can be classified into two types: energetic‐bipolar and small‐bipolar types. Three of them are energetic‐bipolar events, coincident with a high peak‐current LF pulse that originates from a negative return stroke with a peak current larger than 100 kA. The others are small‐bipolar events, followed by a negative bipolar LF pulse with a moderate peak current. Three of the four small‐bipolar events are multi‐pulse TGFs, while all of the energetic‐bipolar events in this study are single‐pulse TGFs. Plain Language Summary: Terrestrial gamma‐ray flashes (TGFs) are a transient high‐energy emission from lightning discharges. While a lot of upward TGFs have been detected by satellites, a few downward TGF have been detected by ground‐based experiments. Our detection network in Japan has detected seven downward TGFs in winter thunderstorms for 4 years. Lightning discharges associated with the downward TGFs were also monitored in the low‐frequency radio band. The low‐frequency pulses associated with the downward TGFs can be classified into two types. Correlation analysis of downward TGFs with gamma‐ray and low‐frequency observations is a powerful approach to reveal the production mechanism of TGFs. Key Points: Downward terrestrial gamma‐ray flashes (TGFs) in winter thunderstorms of Japan can be classified into two types based on low‐frequency (LF) observationsThree events were single‐pulse TGFs coincident with high peak‐current LF pulses of return strokesFour events were followed by moderate peak‐current LF pulses, and three of them are multi‐pulse TGFs [ABSTRACT FROM AUTHOR]

Cosmic‐ray shower, hitting the atmosphere all the time, includes high‐energy electrons. Electric fields in thunderstorms accelerate these electrons so that they can reach farther distances with producing secondary electrons. The strong field above 0.284 MV m−1 causes the Relativistic Runaway Electron Avalanches (RREA) process with an exponential increase of electrons. Even with lower electric fields below this RREA threshold which are usually measured in thunderstorms, an increase in electrons' kinetic energy and production of secondary electrons can occur without avalanche processes, known as Modification Of Spectra (MOS) of the cosmic‐ray shower. Both phenomena are related to observed gamma ray glow, which is bremsstrahlung emission from accelerated electrons in thunderstorms. We calculate an extended range and kinetic energy of electrons below the RREA threshold using an analytical evaluation and Geant4 Monte Carlo simulations. For example, at 0.280 MV m−1 slightly below the RREA threshold, 3 MeV electrons gain 100% of their original kinetic energy through the passage of the continuous slowing down approximation (CSDA) range defined at the null electric field, which is consistent with results in previous studies as the transition to the RREA process. Even at a lower field of 0.260 MV m−1, the energy recovery by the field allows an injected 20 MeV electron beam to extend its average electron range from 73 m, in the null field configuration, to 562 m. We have performed analytical calculation and Geant4 simulations of atmospheric electron behavior for initial electron energy of 0.1–100 MeV and an electric field below 0.290 MV m−1. Key Points: We develop calculations for e− spatial range with electric fields up to the avalanche threshold, 0.284 MV/m, related to gamma ray glowOur particle simulation shows that thunderstorm fields below avalanche level extend the range of 1–100 MeV electrons by a factor of 2–10The calculations indicate a transition to avalanche regime with 3 MeV electron under 0.280 MV/m that extends the spatial range to infinity [ABSTRACT FROM AUTHOR]

Around 17:00 on January 12, 2020 (UTC), radiation detectors installed at two locations with a 1.35 km separation in Kanazawa City, Japan, captured a total of four gamma‐ray enhancements. The first pair was simultaneously observed at the two locations at 17:03 and were abruptly terminated by a lightning discharge. The remaining two enhancements were also nearly simultaneously observed ∼3 min later, and one of them was also terminated by another lightning discharge. At the last termination, a downward terrestrial gamma‐ray flash and a negative energetic in‐cloud pulse were observed. Both pairs were associated with thundercloud cells. In the first pair, simultaneous detection in two locations 1.35 km apart suggests either a gamma‐ray glow emerged in‐between and time variability of its intensity were directly observed or there were two (or more) gamma‐ray glows in the cell which reached the two detectors coincidentally. In the latter pair, the peak time in the downwind detector was ∼40 s later than that of the upwind detector. If the irradiation region moved with the cell, it would have taken ∼110 s. The discrepancy suggests either the glow moved 2.5 times faster than the cell or there were two (or more) glows in the cell. Also, the fact that the thunderstorm cell hosting the latter glows experienced the lightning discharge ∼3 min before suggests that the strong electric field in the cell can develop within a few minutes. Plain Language Summary: Thunderclouds sometime emit gamma rays with a duration of minutes, which are called "gamma‐ray glow". It is bremsstrahlung emission from high‐energy electrons accelerated in the cloud. At around 17:00 (UTC) January 12, 2020, two radiation detectors installed 1.35 km apart in Kanazawa City, Japan, captured a total of four count rate enhancements. The first two disappeared with a lightning discharge, and the last one with another lightning, in this case accompanied by an intense gamma ray flash called a "downward terrestrial gamma‐ray flash" (TGF). The overall behavior is similar to another gamma‐ray glow observed in the same location on January 2018 (e.g. Wada et al. 2019, https://doi.org/10.1038/s42005-019-0168-y). This is also the third report of gamma‐ray glow termination associated with both lightning discharges and TGFs. However, while the 2018 event can be explained well by assuming that the electron acceleration region moves with the thundercloud cell (monitored by rainfall map) and then terminated by a lightning discharge, the time profiles of the four current events cannot. To explain the behavior of the 2020 data, new models such as electron acceleration region(s) rapidly emerging in a thundercloud cell, and/or multiple electron acceleration regions co‐existing in a single cell, are discussed. Key Points: Four gamma‐ray enhancements were observed at two locations 1.35 km apart along the wind direction, and their time profiles were analyzedThe termination of three of them was also recorded. The last one was associated with a downward terrestrial gamma‐ray flash and a negative energetic in‐cloud pulseThe acceleration region of gamma‐ray glows in a thundercloud can develop within a few minutes after experiencing a discharge [ABSTRACT FROM AUTHOR]

During three winter seasons from November 2016 to March 2019, 11 gamma‐ray glows were detected at a single observation site of our ground‐based gamma‐ray monitoring network in Kanazawa, Japan. These events are analyzed with observations of an X‐band radar network, a ceilometer, a disdrometer, and a weather monitor. All the detected glows were connected to convective high‐reflectivity regions of more than 35 dBZ, developed up to an altitude of >2 km. They were also accompanied by heavy precipitation of graupels. Therefore, graupels in the lower layer of thunderclouds that correspond to high‐reflectivity regions can form strong electric fields producing gamma‐ray glows. Also, these events are compared with a limited sample of nondetection cases, but no significant differences in meteorological conditions were found between detection and nondetection cases in the present study. Plain Language Summary: Strong electric fields inside thunderclouds can accelerate electrons to relativistic energies, and gamma‐ray photons from the accelerated electrons can be observed as minute‐lasting "gamma‐ray glows." During winter thunderstorms in Japan, we detected eleven gamma‐ray glows at sea level. The observations were combined with meteorological measurements such as atmospheric temperature, cloud bases, types of precipitation particles, and radar‐echo measurements. All the detected gamma‐ray glows were taking place during a passage of tall and well‐developed radar‐echo regions, and accompanied by heavy precipitation of graupel/hail pellets. The graupel/hail particles in the lower layer of thunderclouds could have contributed to gamma‐ray glows production. Key Points: Eleven gamma‐ray glows were observed during three winter seasons at a single observation site in JapanAll the detected gamma‐ray glows were associated with tall and well‐developed radar‐echo structures of thunderstormsGraupel pallets in the lower layer of thunderclouds could be related to downward electron acceleration for the gamma‐ray glows [ABSTRACT FROM AUTHOR]

Relativistic runaway electron avalanches (RREAs) imply a large multiplication of high‐energy electrons (∼1 MeV). Two factors are necessary for this phenomenon: a high electric field sustained over a large distance and an energetic particle to serve as a seed. The former sustains particle energies as they keep colliding and lose energy randomly; and the latter serves as a multiplication starting point that promotes avalanches. RREA is usually connected to both terrestrial gamma‐ray flashes (TGFs) and gamma‐ray glows (also known as Thunderstorm Ground Enhancement (TGE) when detected at ground level) as possible generation mechanism of both events, but the current knowledge does not provide a clear relationship between these events (TGF and TGE), beyond their possible common source mechanism, still as they have different characteristics. In particular, their timescales differ by several orders of magnitude. This work shows that chain reactions by TGF byproducts can continue for the timescale of gamma‐ray glows and even provide energetic particles as seeds for RREAs of gamma‐ray glows. Key Points: Photonuclear reactions triggered by a terrestrial gamma‐ray flashes (TGF) will sustain a gamma‐ray emission level that can promote new relativistic runaway electron avalanches (RREAs)Both photonuclear reactions and their induced RREA can extend TGF effects to minute timescaleWe evaluate the possibility of gamma‐ray glows promoted by RREAs originating from photonuclear‐induced nuclides decays [ABSTRACT FROM AUTHOR]

We report simulation results of photonuclear reactions in the atmosphere triggered by a downward terrestrial gamma ray flash in lightning. Possible channels of reactions in the atmosphere and their cross‐sections are verified with the ENDF/B‐VII.1 library. Monte Carlo simulations with two stages are then performed with the Geant4 framework. In the first stage, electrons following the relativistic runaway electron avalanche spectrum are produced in a mass model of the atmosphere, and production of photoneutrons and β+‐decay nuclei is calculated based on the nuclear data library. In total 1 × 1013 neutrons and 4 × 1012β+‐decay nuclei are produced by 1018 energetic electrons above 1 MeV. In the second stage, propagation of the photoneutrons and positrons from the β+‐decay nuclei in the previous stage is calculated. As a result, we model on‐ground distributions of fluxes and energy spectra for neutrons, neutron‐related gamma rays, and annihilation ones. The simulation model is to be compared with photonuclear events detected in low‐charge‐center winter thunderstorms. Plain Language Summary: Lightning discharges occasionally emit a powerful flash of gamma rays called terrestrial gamma ray flashes. Gamma rays in terrestrial gamma ray flashes have high energies enough to react with atmospheric nuclei such as nitrogen and oxygen. The nuclear reactions in the atmosphere produce neutrons and unstable isotopes that emit positrons. In this paper, we utilize a Monte Carlo simulation framework, calculate a series of reactions and processes in the atmosphere, and then construct a distribution model of neutrons, neutron‐related gamma rays, and positron‐related ones at ground level. The obtained model can be compared with recent observations of nuclear reactions during winter thunderstorms in Japan. Key Points: Possible channels of atmospheric photonuclear reactions in lightning are surveyed from a nuclear‐reaction data libraryMonte Carlo calculations are performed to simulate photoneutron and β+‐decay‐nuclide productions in the atmosphereOn‐ground distributions of fluxes and spectra for neutrons, neutron‐related gamma rays, and annihilation gamma rays are modeled [ABSTRACT FROM AUTHOR]

During a winter thunderstorm on 6 February 2017 in Japan, photonuclear reactions such as 14N(γ, n)13N were triggered by a downward terrestrial gamma‐ray flash (TGF), as reported by Enoto et al. (2017, https://doi.org/10.1038/nature24630). In the present paper, we compare the observation with a simulation model of downward TGFs and subsequent photonuclear reactions constructed by the first paper of the series and Wada, Enoto, Nakazawa, et al. (2019, https://doi.org/10.1103/physrevlett.123.061103). The observation and model consist of three components: annihilation gamma rays from positrons produced by β+‐decay nuclei, deexcitation gamma rays originating from neutron captures, and radiation doses by TGF photons. Each component of the observation is reproduced by the simulation model, and we constrain a relation between the number of avalanche electrons and their production altitude of the downward TGF. The constraints by three components match within an order of magnitude. The downward TGF is estimated to comprise (0.5–2.5) × 1019 avalanche electrons above 1 MeV produced at an altitude of 1.4–2.7 km. Despite differences in altitude, direction, and season, downward TGFs in winter thunderstorms are thought to have the same mechanism of electron acceleration and multiplication in lightning as TGFs observed by in‐orbit satellites. Plain Language Summary: Lightning flashes are sometimes accompanied by strong high‐energy emission called "terrestrial gamma‐ray flashes" (TGFs). The energy of gamma rays in TGFs is high enough to trigger nuclear reactions with atmospheric nuclei such as nitrogen and oxygen. The nuclear reactions produce neutrons and unstable isotopes that emit positrons. In the companion paper of this series, we calculated the nuclear reactions and propagation processes of their products such as positrons and neutrons and modeled their characteristics at ground level by simulations. In the present paper, the simulation model is compared with the actual observation of a TGF and nuclear reactions during winter thunderstorms in Japan. The model successfully reproduces the observation and estimate the production altitude the number of energetic electrons involved in the TGF. Key Points: A simulation model of photonuclear reactions in lightning is compared with an observation during a winter thunderstorm reported by Enoto et al. (2017, https://doi.org/10.1038/nature24630)Three detected signatures originating from positrons, neutrons, and TGF photons are reproduced by the simulation modelA downward TGF triggering photonuclear reactions comprised 1018 to 1019 avalanche electrons produced at 1.4–2.7 km above sea level [ABSTRACT FROM AUTHOR]

Global hydrological models (GHMs) have become an established tool to simulate water resources worldwide. Most of the GHMs are however uncalibrated and typically use a set of basic hydrological parameters, that could potentially lead to unrealistic projections of the terrestrial water cycle. The calibration of hydrological models is usually performed by using and comparing modeled to observed discharge. Accurate station data and reliable time series data of discharge are, however, often not available for many parts of the world and classic calibration approaches are therefore not feasible. In this paper, we aim to develop a new calibration approach that requires no additional data, is easy to implement, and substantially improves model performance, especially in regions where uncalibrated model performance is rather poor. This is achieved by using the Budyko framework, which provides a conceptual representation of the long‐term water and energy balance. We use a state‐of‐the‐art GHM and calibrate the model within nine river catchments of different sizes and characteristics. Since observed river discharge is available for these catchments, we are able to compare the Budyko‐based calibration approach to a classic discharge‐based calibration scheme and the uncalibrated model version. In all catchments, the Budyko‐based calibration approach decreases biases and increases model performance compared to the uncalibrated model version although performance improvements obtained through a classic calibration approach are greater. Nonetheless, a Budyko‐based calibration is a valuable, intermediate approach between use of a basic set of a priori hydrological parameters and classical calibration against discharge data. Key Points: Most global hydrological models are uncalibrated using predefined sets of basic hydrological parametersWe developed a simple calibration approach that requires no additional data and substantially improves model performanceThe new approach is based on the Budyko framework providing a conceptual representation of the long‐term water and energy balance [ABSTRACT FROM AUTHOR]

During 2017–2018 winter operation of the Gamma‐Ray Observation of Winter Thunderclouds experiment in Japan, two downward terrestrial gamma‐ray flashes (TGFs) that triggered atmospheric photonuclear reactions were detected. They took place during winter thunderstorms on 5 December 2017 and 9 January 2018 at Kanazawa, Ishikawa Prefecture, Japan. Each event coincided with an intracloud/intercloud discharge, which had a negative‐polarity peak current higher than 150 kA. Their radio waveforms in the low‐frequency band are categorized as a distinct lightning type called "energetic in‐cloud pulse" (EIP). Negative‐polarity EIPs have been previously suggested to be highly associated with downward TGFs, and the present observations provide evidence of the correlation between them for the first time. Furthermore, both of the downward TGFs followed "gamma‐ray glows," minute‐lasting high‐energy emissions from thunderclouds. It is suggested that the negative EIPs took place with downward propagating negative leaders or upward positive ones developed in highly electrified regions responsible for the gamma‐ray glows. Plain Language Summary: We observed, on the ground, intense and brief gamma‐ray emissions, called "downward terrestrial gamma‐ray flashes," twice during winter thunderstorms in Japan. They coincided with a kind of in‐cloud lightning discharges called "negative energetic in‐cloud pulses." They have been previously predicted to have a connection to downward terrestrial gamma‐ray flashes, and we observationally confirm the prediction for the first time. Furthermore, the two downward terrestrial gamma‐ray flashes were preceded by weak and minute‐lasting gamma‐ray emissions coming from thunderclouds, called "gamma‐ray glows." High electric fields inside thunderclouds required to produce gamma‐ray glows were thus related to the downward terrestrial gamma‐ray flashes and the negative energetic in‐cloud pulses. Key Points: Two downward terrestrial gamma‐ray flashes detected in Japan were coincident with high peak‐current lightning dischargesThe lightning discharges can be categorized as negative energetic in‐cloud pulsesBoth cases took place in highly electrified regions responsible for production of gamma‐ray glows [ABSTRACT FROM AUTHOR]

Abstract: An on‐ground observation program for high‐energy atmospheric phenomena in winter thunderstorms along the Japan Sea has been performed via measurements of gamma ray radiation, atmospheric electric field, and low‐frequency radio band. On 11 February 2017, the radiation detectors recorded gamma ray emission lasting for 75 s, and then abruptly terminated with a nearby lightning discharge. The gamma ray spectrum extended up to 20 MeV and was reproduced by a cutoff power law model with a photon index of 1 . 3 6 − 0 . 04 + 0 . 03, being consistent with Bremsstrahlung radiation from a thundercloud (known as a gamma‐ray glow or a thunderstorm ground enhancement). The low‐frequency radio monitors, installed ∼50 km away from the gamma ray observation site recorded leader development of an intracloud/intercloud discharge spreading over ∼60 km area with a ∼300‐ms duration. The timing of the gamma ray termination coincided with the moment when the leader development of the intracloud/intercloud discharge passed 0.7 km horizontally away from the radiation monitors. The intracloud/intercloud discharge started ∼15 km away from the gamma ray observation site. Therefore, the glow was terminated by the leader development, while it did not trigger the lightning discharge in the present case. [ABSTRACT FROM AUTHOR]

SUMMARY The Si resonator is applied for measuring the voltage in a highly isolated manner. The working principle is based on the resonant frequency shift caused by the electrical field from the electrode connected to the high-voltage source (supposing the battery). Here, the resonator is electrically floated, and its potential is decided by the relative position against the electrodes which are connected to the high voltage and the driving voltage. The induced voltage on the resonator is analyzed against the driving frequency. The resonance is found by the paired peaks in the amplitude curve. The setup for the electrical measurement can make the sensor system compact. A new sensor design for avoiding the electrical field concentration realizes the measurement over 400 V without the breakdown. This will match with the high-voltage dc power supply system. [ABSTRACT FROM AUTHOR]

Congenital disorders of glycosylation (CDG) are a group of hereditary metabolic diseases characterized by abnormal glycosylation of proteins and lipids. Often, multisystem disorders with central nervous system involvement and a large variety of clinical symptoms occur. The main characteristics are developmental delay, seizures, and ataxia. In this paper we report the clinical and biochemical characteristics of a 5-year-old girl with a defective galactosylation of N-glycans, resulting in developmental delay, muscular hypotonia, epileptic seizures, inverted nipples, and visual impairment. Next generation sequencing revealed a de novo mutation (c.797G > T, p.G266V) in the X-chromosomal gene SLC35A2 (solute carrier family 35, UDP-galactose transporter, member A2; MIM 300896). While this mutation was found heterozygous, random X-inactivation of the normal allele will lead to loss of normal SLC35A2 activity in respective cells. The functional relevance of the mutation was demonstrated by complementation of UGT-deficient MDCK-RCA and CHO-Lec8 cells by normal UGT-expression construct but not by the mutant version. The effect of dietary galactose supplementation on glycosylation was investigated, showing a nearly complete normalization of transferrin glycosylation. [ABSTRACT FROM AUTHOR]

The conserved oligomeric Golgi (COG) complex is involved in intra-Golgi retrograde trafficking, and mutations in six of its eight subunits have been reported in congenital disorders of glycosylation (CDG). Here we report a patient showing severe acquired microcephaly, psychomotor retardation, seizures, liver dysfunction, hypocupremia, and hypoceruloplasminemia. Analysis of his serum glycoproteins revealed defects in both sialylation and galactosylation of glycan termini. Trio-based whole-exome sequencing identified two heterozygous mutations in COG2: a de novo frameshift mutation [c.701dup (p.Tyr234*)] and a missense mutation [c.1900T > G (p.Trp634Gly)]. Sequencing of cloned reverse-transcription polymerase chain reaction (RT-PCR) products revealed that both mutations were located on separate alleles, as expected, and that the mutant transcript harboring the frameshift mutation underwent degradation. The c.1900T > G (p.Trp634Gly) mutation is located in a domain highly conserved among vertebrates and was absent from both the public database and our control exomes. Protein expression of COG2, along with COG3 and COG4, was decreased in fibroblasts from the patient. Our data strongly suggest that these compound heterozygous mutations in COG2 are causative of CDG. [ABSTRACT FROM AUTHOR]

Aim To investigate the relationship between plasma betatrophin concentrations and insulin secretion capacity in people with Type 2 diabetes. Methods Glucagon stimulation tests (1 mg) were performed in 70 people with Type 2 diabetes after an overnight fast. Plasma betatrophin concentrations were measured using an enzyme-linked immunosorbent assay. Insulin secretion capacity was evaluated by measuring increments of C-peptide concentration in response to glucagon stimulation, and creatinine clearance was determined by comparing creatinine concentrations in serum and 24-h urine samples. Results Plasma betatrophin concentrations were positively correlated with duration of Type 2 diabetes ( r = 0.34, P = 0.003), and negatively correlated with increments of C-peptide concentration ( r = 0.37, P = 0.001) and creatinine clearance ( r = 0.37, P = 0.001). The correlation with increments of C-peptide concentration remained significant after adjustment for age and duration of Type 2 diabetes ( r = 0.25, P = 0.037). Multivariate analysis identified age and increments of C-peptide concentration as independent factors associated with plasma betatrophin levels. Conclusion Plasma betatrophin levels inversely correlate with insulin secretion capacity, suggesting that betatrophin levels are regulated by insulin secretion capacity in humans. [ABSTRACT FROM AUTHOR]

The first stainless-steel microchannel (MC) emulsification chips with grooved MC arrays, each consisting of uniform-sized parallel channels and a terrace, were developed. These chips enabled successful spontaneous-transformation-based generation of uniformly sized droplets of soybean oil and silicone oil. As for the influence of the dispersed-phase velocity in a channel, the critical velocity below which uniform-sized droplets were obtained from the channels depended on the interfacial tension between two phases. The maximum productivity of uniform-sized oil droplets for the stainless-steel MC emulsification chips was estimated to be several milliliters per hour. An adapted capillary number that considers the wettability of the dispersed phase of two different oils could be useful for understanding the flow state of the dispersed phase during droplet generation. [ABSTRACT FROM AUTHOR]

Neuro-Behçet's disease (NBD) is a serious complication of Behçet's disease. Generally, NBD patients with a chronic course are refractory to immunosuppressive treatment, resulting in the deterioration of personality. In this study, levels of B cell-activating factor belonging to the TNF family (BAFF) were measured in the cerebrospinal fluid (CSF) from 18 patients with NBD, 27 patients with epidemic aseptic meningitis (AM), 24 patients with multiple sclerosis (MS) and 34 healthy controls. BAFF levels in patients with NBD were significantly elevated compared with healthy controls, but showed no statistically significant elevation compared with either of the disease controls. In contrast, CSF IL-6 levels were slightly elevated in patients with NBD and significantly elevated in patients with AM and MS compared with healthy controls. Patients with NBD were subdivided into two groups according to their clinical course (eight patients with a slowly progressive course presenting with psychosis and dementia and 10 patients with an acute course including aseptic meningitis, brainstem involvement and myelopathy). BAFF levels were significantly increased in those with a slowly progressive course compared with those with an acute course. CSF BAFF levels did not correlate with serum BAFF levels, CSF cell counts or CSF IL-6 levels in patients with NBD. These data suggested that BAFF was produced within the central nervous system and may be associated with the development of NBD, particularly with a progressive course. [ABSTRACT FROM AUTHOR]

The purpose of this study was to establish a method for imaging the process of gastrointestinal (GI) absorption and subsequent biodistribution in the human body after oral drug administration, using positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). First, we developed a method to deliver the radiotracer safely into the stomach using soft gelatin capsules to avoid any significant exposure to the pharyngoesophageal region. Second, we performed pharmacokinetic (PK) analyses on time-radioactivity profiles in GI tissues and blood to calculate the gastric emptying and intestinal elimination rate constants and to estimate the fluid volume in the lumen of the small intestine from PET image analysis. This is the first study involving oral administration of a PET probe in humans, and the results demonstrate the high potential of PET technology to investigate the GI absorption and PK profiles of drugs in humans. [ABSTRACT FROM AUTHOR]

Cutaneous Malassezia is an exacerbating factor in patients with atopic dermatitis. We analysed the Malassezia microbiota of adult patients with head and neck atopic dermatitis of different severities (mild, moderate and severe). Of the nine human-associated Malassezia species, the number detected was similar (3.5-4.2 species per case) among the members of all severity groups. However, the ratio of the two major Malassezia species, M. globosa and M. restricta, was different in the severe group. [ABSTRACT FROM AUTHOR]

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The current status of replacement therapy for haemophilia and the role played by nurses in Japan were investigated at 16 facilities (17 specialties) each providing care to 20 or more haemophilia A or B patients without inhibitor. The questionnaire was mailed to the nurse or physician in charge of haemophilia at each facility in August 2006, asking the nurse to fill in the questionnaire. Responses were collected on 1318 patients (haemophilia A: 1078 patients; haemophilia B: 240 patients). About 70% of these patients were reported to be severe haemophilia A or B. Overall, 26% were receiving regular prophylaxis while 74% received on-demand therapy with or without temporary prophylaxis before special events. The percentage of patients receiving primary prophylaxis was only 2%. The percentage of adherence to prophylaxis decreased with age (lowest at age 19–29) but this percentage for each age group in Japan was higher than that in the western countries. Of the nurses working at the facilities surveyed, 88% considered prophylaxis as an optimal therapy for severe haemophilia patients, although the percentage of patients receiving prophylaxis for the entire population surveyed was lower than that in the western countries. The main factor precluding introduction of prophylaxis was ‘difficulty in venous access’ for infants and small children. On the other hand, ‘unwillingness of family members’ and ‘poor adherence’ were the main factors precluding introduction of this therapy for those aged over 6 years. [ABSTRACT FROM AUTHOR]

Nine of 250 cows on a dairy farm initially developed severe dermatitis on parts of their bodies that touched the floor, and it then spread over their entire body. The cause was suspected to be calcium cyanamide, which had been added to the material spread on the floor to prevent environmental mastitis. Experimental exposure of the skin of a cow to calcium cyanamide induced the same type of contact dermatitis, and histopathological investigations showed that it caused irritant and allergic reactions. To identify the cause of the dermatitis, a patch test with calcium cyanamide and its breakdown products, cyanamide, urea and ammonium bicarbonate, was carried out on four cows. Three of them had a positive reaction to calcium cyanamide and cyanamide; delayed and amplified reactions suggesting an allergic response were observed. [ABSTRACT FROM AUTHOR]

Studies with green fluorescent protein (GFP) have revealed the subcellular distribution of many steroid hormone receptors to be much more dynamic than previously thought. Fluorescence resonance energy transfer (FRET) and fluorescence recovery after photobleaching (FRAP) are powerful techniques with which to examine protein–protein interaction and the mobility of tagged proteins, respectively. FRET analysis revealed that steroid treatment (with corticosterone or testosterone) induces direct interaction of the glucocorticoid receptor (GR) and importin α in the cytoplasm and that, shortly after nuclear entry, the GR detaches from importin α. The mineralocorticoid receptor (MR) and androgen receptor (AR) show the same trafficking. Upon oestradiol treatment, ERα and ERβ in the same cell are relocalised to form a discrete pattern and are localised in the same discrete cluster (subnuclear foci). FRAP analysis showed that nuclear ERα and ERβ are most dynamic and mobile in the absence of the ligand, and that mobility decreases slightly after ligand treatment. Genomic as well as non-genomic actions of steroid hormones influence the cellular function of target tissues spacio-temporally. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the neuroprotective effect of chronically or acutely administered lithium against hypoxia in several brain regions. Furthermore, we investigated the contribution of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and cAMP response element binding protein (CREB) to the neuroprotective effect of lithium. Methods: Brain slices were prepared from rats that had been treated chronically or acutely with lithium. The cerebral glucose metabolic rate (CMRglc) before and after hypoxia loading to brain slices was measured using the dynamic positron autoradiography technique with [18F]2-fluoro-2-deoxy-d-glucose. The changes of expression of proteins were investigated using Western blot analysis. Results: Before hypoxia loading, the CMRglc did not differ between the lithium-treated and untreated groups. After hypoxia loading, the CMRglc of the untreated group was significantly lower than that before hypoxia loading. However, the CMRglc of the chronic lithium treatment group recovered in the frontal cortex, caudate putamen, hippocampus and cerebellum, but not in the thalamus. In contrast, the CMRglc of the acute lithium treatment group did not recover in any analyzed brain regions. After chronic lithium treatment, the levels of expression of BDNF and phospho-CREB were higher than those of untreated rats in the frontal cortex, but not in the thalamus. However, the expression of NGF did not change in the frontal cortex and thalamus. Conclusions: These results demonstrated that lithium was neuroprotective against hypoxia only after chronic treatment and only in specific brain regions, and that CREB and BDNF might contribute to this effect. [ABSTRACT FROM AUTHOR]

To investigate the effects of castration on the expression of endothelins (ETs), ET receptors and ET converting enzyme-1 (ECE-1) in the rat seminal vesicle (RSV). Sprague-Dawley rats (3 months old) were surgically castrated or sham-operated, and then killed 7 days after surgery. Biochemical and pharmacological properties and the location of ET receptors in the RSV were determined by a series of binding experiments with [125I]ET-1, using membrane particulates and slide-mounted frozen sections of RSV. Expression levels of ETA and ETB receptor subtypes, ET-1, ET-3 and ECE-1 mRNAs were assessed by relative multiplex reverse-transcription polymerase chain reaction (RT-PCR). The density of total ET receptors increased significantly in the seminal vesicle of the castrated rat. The predominance of the ETA receptor subtype in the RSV did not change with castration. Autoradiographic studies showed the presence of ET receptors on the smooth muscle and epithelium of the RSV. In addition, RT-PCR showed an up-regulation in the expression of ETA and ETB receptor subtypes, ET-1 and ECE-1 mRNAs in the seminal vesicle of the castrated rat. However, castration caused no significant change in the expression levels of ET-3 mRNA. These findings suggest a regulatory role for testosterone in the expression of the ET receptor system in the RSV. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the potential of p21 as a gene therapy treatment for prostate cancer, by introducing p21 into both androgen-dependent (AD) and -independent (AI) human prostate cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p21, carrying human p21 cDNA. MATERIALS AND METHODS The LNCaP, DU145 and PC-3 human prostate cancer cell lines were cultured and infected with Ad5CMV-p21. Cell growth, cell-cycle progression and tumorigenicity were then assessed by thymidine incorporation into cellular DNA, and cell number, flow cytometry, and tumour growth after inoculating the cells into nude mice. RESULTS Growth was inhibited in Ad5CMV-p21 viral-infected AD and AI prostate cancer cells. The effects were dose-dependent, regardless of the androgen status of the cell lines. Flow cytometric analysis showed that Ad5CMV-p21 arrested cell-cycle progression at G1/S with no appreciable effect on the levels of apoptotic cells. The tumorigenicity of cancer cells infected with Ad5CMV-p21 was greatly reduced in athymic mice. CONCLUSIONS These results suggest that Ad5CMV-p21 may be a new therapeutic agent for human prostate cancer gene therapy. [ABSTRACT FROM AUTHOR]

Summary The development of informative polymorphic markers is essential for QTL mapping. We developed 50 microsatellite markers from BAC clones containing genes that were predicted to map swine chromosome 4 (SSC4) according to comparative analysis between human and swine chromosomes, and constructed a linkage map that consisted of 37 markers including 24 markers closely linked to genes in BAC clones. Microsatellite markers were developed by direct-sequencing of BAC clones and our results demonstrated that this method was effective for developing microsatellite markers in specific regions on chromosomes. Effective development of microsatellite markers closely linked to genes can further accelerate the comparative studies of chromosomes between different species. [ABSTRACT FROM AUTHOR]

Objective To examine the effect of age on the biochemical and functional properties, and regional distribution of endothelin (ET) receptors in the rabbit renal pelvis. Materials and methods The properties of ET receptors in 6-week-old and 6-month-old male rabbit renal pelves were examined using isolated muscle-bath and radioligand receptor-binding techniques. Results ET-1 caused a significant increase in the contractile force in muscle strips from all regions of the renal pelvis from both age groups, with the following rank order: upper = middle > lower. The magnitude of the ET-1-induced contractile responses were similar in the lower pelvic regions in both ages, but the responses in the upper and middle regions were significantly greater in younger rabbits. ET-1 increased the frequency of spontaneous activity in a concentration-dependent manner in the upper and middle pelvic regions in both age groups, with significantly smaller ED50 values in the younger than in the older rabbits. In both age groups the lower pelvic region lacked spontaneous activity. The density of total ET receptors was higher in the upper and middle regions of the renal pelvis than in the lower renal pelvis of both ages, with the density in the upper and middle regions being greater in older than in younger rabbits. In all regions, ET subtype selective compounds inhibited [125I]ET-1, binding consistent with the predominance of the ETA receptor subtype, except in the lower region of the older rabbits, in which the densities of ETA and ETB subtypes were similar. In all regions, the younger renal pelvis contained a higher proportion of ETA receptors than in older tissues. Light microscopic autoradiographic data indicated the presence of ETA and ETB receptors in smooth muscle and epithelial cells, respectively. Conclusion These data indicate the presence of regional differences in the density of ET receptors and in the contractile responses to ET-1 in rabbit renal pelvis, and that although older rabbit renal pelvis contains more total ET receptors than younger renal pelvis, the latter had a higher portion of the ETA receptor subtype and the younger tissues were more responsive to ET-1. [ABSTRACT FROM AUTHOR]

Unlabelled: BACKGROUND AND OBJECTIVES Geriatric depression is often thought to differ from that at other times of adulthood. Recently, several studies have shown that the incidence of white matter hyperintense lesions identified by brain MRI is higher in patients with geriatric depression than in healthy elderly subjects, but a consensus has not yet been reached on the relationship between the severity of white matter lesions and either cognitive impairment or depressive symptoms.Method: Forty-seven patients aged 50 to 75 years with major depression were divided into two groups based on age at onset of depression: early-onset (< 50 years) group (20 patients; mean age, 62.7 +/- 6.7) and late-onset (> or =50 years) group (27 patients; mean age, 65.6 +/- 5.4). The severity of hyperintense white matter lesions on MRI was classified by region, then a proton magnetic resonance spectroscopy ((1)H-MRS) focusing on the white matter of the frontal lobes, multidimensional neuropsychological tests and evaluation of depressive symptoms were conducted.Results: The severity of the deep white matter lesions, the deterioration of cognitive function related to subcortical/frontal brain system and clinician-rated depressive symptoms were all more pronounced in the late-onset group compared with those in the early-onset group. It was further observed that the more severe the deep white matter lesions, the lower the levels of N-acetylaspartate/creatine. With the age of onset as the covariate, the patients with moderate deep white matter lesions had more pronounced cognitive impairment and clinician-rated depressive symptoms than those with none and/or mild lesions.Conclusion: These results suggest that subcortical/frontal type cognitive impairment and the persistence of depressive symptoms in geriatric depression is related to moderate deep white matter lesions more often complicated in the late-onset group. The (1)H-MRS findings were suggested to be a useful indicator of neuronal/axonal loss in the white matter of the frontal lobes which precedes cognitive impairment. [ABSTRACT FROM AUTHOR]

Identifies the genetic regions in the swine genome that are responsible for economically important traits. Implementation of a quantitative trait loci (QTL) analysis by mating two female Meishan pigs with a male Gottingen pig; Effects of QTL for vertebra number on chromosomes one and two; Environmental effects included in the model of QTL analysis.

Objective To assess fibroblast growth factor‐2 (FGF2/bFGF), which is important in the development and maintenance of the normal prostate and in the development of human benign prostatic hyperplasia (BPH) and prostatic carcinoma, in an animal model of experimentally induced diabetes. Materials and methods Using Western blotting and immunohistochemical analyses, the expression of FGF2 in prostates from several groups of rats was investigated. Rats had diabetes for 8 or 16 weeks (induced by intravenous injection with 65 mg/kg streptozotocin); rats were also treated with insulin (starting 8 weeks after the induction of diabetes, for 8 weeks), and two further groups acted as age‐matched control rats. Immunohistochemical markers for smooth muscle (α‐actin) and epithelium (cytokeratin) were used to distinguish different cell types in adjacent prostatic sections. Results Diabetic rats had smaller prostates and lower serum testosterone levels than their controls; insulin treatment of diabetic rats increased prostatic size and testosterone levels. As shown by Western blotting, diabetes caused greater FGF2 expression than in controls, whereas reverse‐transcriptase polymerase chain reaction studies showed similar levels of prostatic FGF‐2 mRNA in all groups. Immuno‐histochemical studies showed that FGF‐2 was expressed in both stromal and epithelial components of the rat prostate. Furthermore, although the expression of FGF2 was higher in epithelial than stromal cells in control prostates, it was distributed uniformly in the diabetic prostate. Conclusion The differences in the level of expression and pattern of distribution of FGF2 suggests a potential role for FGF2 in the changes observed in prostatic growth in diabetic rats. [ABSTRACT FROM AUTHOR]

A resource family of pigs has been constructed by using a boar of Göttingen miniature pig and two sows of Meishan pig as parents. In the construction of the family, two F1 males and 18 F1 females were intercrossed to generate 143 F2 offspring. The members of the family were genotyped using 243 genetic markers including 26 markers developed in our laboratory in order to generate a linkage map of markers for use in detecting quantitative trait loci (QTLs) in the family. The markers consisted of 237 microsatellites, five PRE-1 markers, and one RFLP marker. The linkage map was revealed to cover all 18 autosomes and the X chromosome; and the total length of the sex-averaged linkage map was calculated to be 2561 ·9 cm. Four out of the 26 markers developed in our laboratory ex-ended the current linkage map at the termini of chromosomes 1p, 5p, 11p, and Xq. The linkage maps of all the chromosomes except for chromosome 1 were found to be longer in females than in males. Concerning chromosome 1, the length of the linkage map showed no difference between females and males, which was attributed to low recombination rates between markers localized in the centromeric region in females. The average ratio of female-to-male recombination was calculated to be 1 ·55. [ABSTRACT FROM AUTHOR]

Introduction: The acrosin gene (ACR) has been assigned to the terminal region of swine chromosome 5 p-arm, p15, by fluorescence in situ hybridization[sup 1.] The aconitase gene (ACO2) was assumed to map to the p telomeric region of chromosome 5, on the basis of its position in linkage map[sup 1,2.] In order to explore the arrangement of ACO2 and ACR on the chromosome and in the linkage map, we have molecularly cloned porcine genomic fragments containing at least a part of the ACO2 and ACR genes. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between genomic heterogeneity and tumour grade, stage and DNA content in 30 transitional cell carcinomas (TCCs) of the urinary bladder. Materials and methods Tissue specimens from 30 patients (25 men and five women) with newly diagnosed TCC of the urinary bladder were examined for genomic heterogeneity using fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes; the copy number of pericentromeric sequences on chromosomes 7, 9 and 17 was detected within interphase nuclei in contact preparations from the tumour specimens. Results The aneusomy of chromosomes 7, 9 and 17 was significantly higher in aneuploid than in diploid tumours ( P<0.001). Tumour grade and stage were strongly associated with aneusomy for chromosome 17 ( P<0.01, P<0.001, respectively). The aneusomy of chromosomes 7 and 9 were significantly correlated with increasing tumour stage ( P < 0.001), but not with tumour grade. Conclusion These results suggest that the measurement of aneusomy using FISH, especially for chromosome 17, in bladder cancer may offer a new objective and quantitative assay of the biological potential of individual tumours. [ABSTRACT FROM AUTHOR]

Objective To analyse the clinical and therapeutic consequences of bacillus Calmette-Guérin (BCG) perfusion therapy for carcinoma in situ (CIS) of the upper urinary tract. Patients and methods Eight pyelo-ureteric systems in five patients with cytologically confirmed CIS of the upper urinary tract were treated using perfusion of BCG through a percutaneous nephrostomy tube in five and a retrograde ureteric catheter in three. Follow-up cystoscopy, retrograde pyelography and selective urinary cytology were obtained 4 weeks after the last treatment and every 3 months thereafter. Results In three patients (five pyelo-ureteric systems) the cytology remained negative for 10-46 months after the treatment was completed. The remaining two patients (three pyelo-ureteric systems) had persistently positive cytology. Of two patients who received BCG therapy through a ureteric catheter, one developed a ureteric stricture and the other developed renal tuberculosis. Conclusions Although long-term adaptation to a nephrostomy tube disturbs the quality of life of the patient, percutaneous perfusion therapy through a nephrostomy tube seems to be safer than retrograde perfusion through a ureteric catheter. [ABSTRACT FROM AUTHOR]