Search for the Pair Production of Dark Particles X with K_{L}

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

Study of the K_{L}→π

The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

Search for K_{L}→π

A search for the rare decay K_{L}→π^{0}νν[over ¯] was performed. With the data collected in 2015, corresponding to 2.2×10^{19} protons on target, a single event sensitivity of (1.30±0.01_{stat}±0.14_{syst})×10^{-9} was achieved and no candidate events were observed. We set an upper limit of 3.0×10^{-9} for the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level (C.L.), which improved the previous limit by almost an order of magnitude. An upper limit for K_{L}→π^{0}X^{0} was also set as 2.4×10^{-9} at the 90% C.L., where X^{0} is an invisible boson with a mass of 135 MeV/c^{2}.

Search for the rare decays K(L)→π0π0µ+µ- and K(L)→π0π0X0→π0π0µ+µ-.

The KTeV E799 experiment has conducted a search for the rare decays, K(L)→π(0)π(0)µ(+)µ(-) and K(L)→π(0)π(0)X(0)→π(0)π(0)µ(+)µ(-), where the X(0) is a possible new neutral boson that was reported by the HyperCP experiment with a mass of (214.3 ± 0.5) MeV/c(2). We find no evidence for either decay. We obtain upper limits of Br(K(L)→π(0)π(0)X(0)→π(0)π(0)µ(+)µ(-)) < 1.0 × 10(-10) and Br(K(L)→π(0)π(0)µ(+)µ(-)) < 9.2 × 10(-11) at the 90% confidence level. This result rules out the pseudoscalar X(0) as an explanation of the HyperCP result under the scenario that the dsX(0) coupling is completely real.

Measurements of the decay KL-->e+ e- gamma.

The E799-II (KTeV) experiment at Fermilab has collected 83 262 K(L)-->e+ e- gamma(gamma) events above a background of 79 events. We measure a decay width, normalized to the K(L)-->pi0pi0pi(D)0 (pi0-->gammagamma, pi0-->gammagamma, pi(D0-->e+ e- gamma(gamma)) decay width, of Gamma(K(L)-->e+e-gamma(gamma))/Gamma(K(L)-->pi0pi0pi(D)0)=(1.3302+/-0.0046(stat)+/-0.0102(syst)) x 10(-3). We also measure parameters of two K(L)gamma*gamma form factor models. In the Bergström-Massó-Singer parametrization, we find Calpha(K*)= -0.517 +/- 0.030(stat) +/- 0.022(syst). We separately fit for the first parameter of the D'Ambrosio-Isidori-Portolés model and find alpha(DIP)= -1.729 +/- 0.043(stat) +/- 0.028(syst).

Nuclear localisation of glutathione S-transferase pi is an evaluation factor for drug resistance in gynaecological cancers.

AIMS: Nuclear glutathione S-transferase pi (GST7pi) has been reported to protect cancer cells against anticancer drugs. The aim of the present study was to evaluate the clinical significance of nuclear GSTpi in gynaecological cancer. MATERIALS AND METHODS: We carried out an immunohistochemical analysis of GSTpi, and examined the correlation between nuclear GSTpi: expression and prognosis in 43 epithelial ovarian cancers. We compared expression levels before and after chemotherapy in uterine cervical cancers and endometrial cancers. RESULTS: The 5-year progression-free survival rate of the nuclear GSTpi-positive group was lower than that of the cytoplasmic GSTpi-positive group, and was significantly lower than that of the negative group (14.3% vs 34.8% vs 66.7%; P = 0.041). The expression of nuclear GSTpi was compared before and after chemotherapy in uterine cervical and endometrial cancers. In eight out of 12 cases (66.7%), the expression turned positive after the chemotherapy. CONCLUSIONS: We suggest that nuclear localisation of GSTpi is associated with drug resistance. The nuclear localisation of GSTpi in tumour cells is a useful prognosticator, and may contribute to the selection of anticancer drugs for gynaecological cancers.

Ion-selective microelectrodes to study proton and bicarbonate transport in the renal epithelium.

We have developed several kinds of ISM, and obtained valuable information. The method presented provides (1) the data in situ, and (2) simultaneous data of the membrane potential and the selected ionic activities. Both of these give the driving forces for ion fluxes across the individual membrane border. They provide not only the knowledge of ionic status in minute spaces but also the relationship between different ionic species which are measured simultaneously in the living cell. Further information could also be available by employing this ISM method in combination with the relevant techniques, such as patch-clamp and fluorescent dye techniques.

Analysis of gas chromatography/electron capture detector sensitive substances in human serum in relation to the determination of iodochlorhydroxyquin concentration.

We found that human sera can be divided into five types depending on the gas chromatography/electron capture detector (GC/ECD) chromatogram pattern. A preliminary GC/MS study on one of the GC/ECD peaks has suggested the presence of a hitherto unknown iodine-containing substance of probably endogenous origin.

The effect of diffusible ions on the peritubular membrane potential of proximal tubular cells in perfused bullfrog kidneys.

Effects of extracellular diffusible ions, such as K+, Cl- and HCO3- (pH), on the peritubular membrane potential (EM) and intracellular activities of K+, (K)i, or Cl-, (Cl)i, were studied in the perfused proximal tubule of bullfrog kidneys with K+ or Cl- -selective microelectrodes. In steady-state conditions, in which both the peritubular and luminal sides were perfused with control Ringer solutions, the K+ equilibrium potential (EK) always exceeded the EM by approximately 19 mV and correlated well with the EM (correlation coefficient r = 0.78), whereas no correlation was recognized between the equilibrium potential of Cl-(ECl) and the EM. In the quick peritubular perfusion experiments, in which the extracellular diffusible ions were changed, the (K)i and (Cl)i were maintained relatively stable. The following facts were observed: (1) At constant EK, decreasing the peritubular chloride (Cl)e produced a small degree of hyperpolarization of the EM instead of depolarization. (2) At constant ECl, increasing the (K)e depolarized the EM. (3) At constant PCO2, the EM was depolarized with low HCO3- (acid) perfusions, while it was hyperpolarized with high HCO3- (alkaline) perfusions. These results are in agreement with the views that, 1) intracellular K+ in the proximal tubule is maintained by an uphill uptake mechanism on the peritubular cell membrane, (2) the ionic conductance of peritubular membrane is relatively high to K+, but low to Cl-, and (3) the pH gradient across the peritubular membrane can modulate the passive permeability to Na+ or K+.

The effect of cAMP on ion transport in the proximal tubular cells in bullfrog kidney.

UNLABELLED: Using a direct cellular micropuncture technique with double-barreled ion-selective microelectrodes, we investigated the effect of dibutyryl-cyclic AMP (db-cAMP) on the membrane potential and the transport of Na+, K+, and H+ in doubly-perfused bullfrog proximal tubules. The peritubular membrane potential difference (EM) and the intracellular K+, Na+ activities ((K)i, (Na)i) or intracellular and luminal pH were monitored continuously after peritubular administration of db-cAMP (10(-3)-10(-4)M). RESULTS: 1) db-cAMP hyperpolarized the EM by 8.0 mV with an increase of (K)i by 4.8 mEq/l; 2) the peritubular administration of high K+ (13.5 and 50 mM) solutions depolarized the EM by 11.5 and 41.5 mV, respectively. The high K+ perfusate with db-cAMP produced a depolarization to the same level as that in simple high K+ perfusion without db-cAMP; 3) db-cAMP transiently blocked the luminal acidification concomitantly with a cellular alkalinization by about 0.1 pH; and 4) db-cAMP caused a decrease of (Na)i by 5.0 mEq/l. CONCLUSIONS: 1) cAMP causes an increase of K+ permeability in the peritubular membrane; 2) cAMP induces a cytosol alkalosis by enhancing incorporation of H+ into the subcellular vesicles, thus favoring the activation of Na+/K+ pump; and 3) cAMP, in effect, suppresses the Na+/H+ exchange mechanism in the luminal membrane and transiently blocks the proximal urinary acidification.

Acid-induced two-step depolarization in the peritubular membrane of bullfrog kidney proximal tubules.

Using ion-selective microelectrode technique, we investigated acid-induced changes of peritubular membrane potential (EM) and intracellular activity of Na+ and H+ ((Na)i and pHi) in the proximal tubule of perfused bullfrog kidney in vivo. When peritubular pH was reduced at constant PCO2, EM was depolarized in two steps: i.e., an initial sharp fall followed by an additional deeper fall. This was termed as the acid-induced two-step depolarization. During this change, pHi was decreased gradually from 7.4 to 6.9 in response to 1/10 HCO3- reduction (pH from 7.7 to 6.7), whereas (Na)i was increased after a transient decrease. This result supports the peritubular rheogenic HCO3- exit coupled to Na+ movement during the initial depolarization period. Complete removal of peritubular HCO3- at constant pH produced a less marked initial depolarization with a transient rise of pHi, followed by a partial repolarization without appreciable change in (Na)i. Peritubular SITS administration inhibited these depolarization responses to the acid perfusion. The above findings suggest that 1) the initial part of the two-step EM depolarization produced by low HCO3- or HCO(3-)-free perfusion resulted mainly from the peritubular rheogenic exist of HCO3-, 2) the magnitude of initial depolarization would also be affected by pHi, and 3) the subsequent delayed changes of EM were mainly determined by the pHi-sensitive K+ conductance of the peritubular membrane.

Functional significance of K+ and Cl- channels in volume regulation in proximal tubular cells.

Using the patch-clamp technique to cultured opossum kidney (OK) cells, we measured the activities of K+ channel and Cl- conductance during hyposmotic stress. The results are as follows: 1) A 50% lowered osmolarity of bath media induced a biphasic change of the membrane potential (EM): early hyperpolarization and late depolarization. The former transient response was abolished by removing Ca2+ from the cellular media, whereas the latter slow response was blocked by DIDS. 2) The hyposmosis-induced change of EM was due to K+ channels activated by cytosolic Ca2+. 3) In hyposmotic media, Cl- current was effectively increased, and this effect was abolished by Cl- channel blockers. 4) The hyposmosis-induced Cl- conductance was inhibited in the cytosolic acid media. In the alkaline media, it was enhanced even without hyposmotic stress. We conclude that the hyposmosis-induced activation of Cl- conductance, being stimulated by alkaline cell pH and inhibited by acid cell pH, may contribute to the ion transport and cell volume regulation along with the Ca(2+)-activated K+ channel.

Role of pH-sensitive ion channels in regulation of cell volume in opossum kidney cells.

Applying the patch-clamp technique to cultured opossum kidney (OK) cells, we investigated effects of pH on the activation of Cl- channels induced by a hyposmotic shock. The Cl- conductance of cell membranes was measured in 145 mM NMG-Cl solution with the whole-cell configuration. Under control conditions, the Cl- conductance was almost negligible. When the cell was exposed to a hyposmotic medium, the Cl- conductance was remarkably elevated. This conductance change was reversibly inhibited by Cl- channel inhibitors, such as DIDS. The activation (pHi) from 7.3 to 7.0, but not influenced by changing the bath pH (pHe). We conclude that the Cl- channel activation by a hyposmotic challenge is highly sensitive to pHi.

Relationship between cytosolic activities of calcium and pH in frog proximal tubules.

To examine the effect of acid-base changes on the cytosolic calcium activity, (Ca)i, we used ion-selective microelectrodes in doubly perfused preparations of bullfrog kidney proximal tubule. For analyzing the time course of changes in (Ca)i and cytosolic pH (pHi) in response to peritubular acid or alkali perfusion and high K+, low Na+, or low Ca2+ perfusion single-barreled PVC-resin Ca2(+)-selective microelectrodes and double-barreled pH-sensitive microelectrodes were inserted into the cells. Control values (mean +/- S.E., number of observations) of (Ca)i and pHi averaged 17.2 +/- 1.0 nM (n = 25) and 7.39 +/- 0.01 (n = 25), respectively. Peritubular perfusion with a low pH perfusate (low HCO3-, pH 6.7) was found to reduce (Ca)i to about 4 nM in association with a moderate degree of cell acidification (to pH 7.09) and depolarization of the peritubular membrane potential (control -60 mV to experimental approximately -40 mV). Further, peritubular alkalinization (high HCO3- 30 mM, pH 8.0) induced a transient elevation of (Ca)i and hyperpolarization. In contrast, the peritubular perfusion of high K+ solution induced a rise of (Ca)i and pHi with membrane depolarization, while low Na+ perfusion decreased (Ca)i and pHi. These results support the view that 1) the experimentally induced changes in the membrane potential may be ascribed in large part of alterations of pH-sensitive conductance across the peritubular membrane, and 2) the cell pH and extracellular Ca2+ affect the cytosolic Ca2+ of the proximal tubule.

[The antibacterial activity of new cephem antibiotics against clinical isolates. A comparison of the antibacterial activity of cefotaxime with 6 other antibiotics].

During the period from May through July 1981, a comparative study was carried out on the antibacterial activities of cefotaxime (CTX) and ceftizoxime (CZX), cefoperazone (CPZ), latamoxef (LMOX), cefotiam (CTM), cefmetazole (CMZ) and cefazolin (CEZ). CTX and these other cephem antibiotics were tested against fresh clinical isolates which had been obtained from clinical materials by the laboratories of 14 participating medical institutions. 1. The clinical isolates were obtained from various clinical materials in the following decreasing order: urine, sputum and pus/discharge; 85.7% of the isolates came from these materials. 2. Concerning the sources of each species of clinical isolates, it was found that P. aeruginosa was isolated from the greatest number -9- of different clinical materials. This was followed by E. coli and E. cloacae, each isolated from 8 different clinical materials, and C. freundii and E. aerogenes, each found in 7 different clinical materials. 3. In relation to S. pyogenes, S. agalactiae and S. pneumoniae, CTX showed the best antibacterial activity; the second most potent antibiotic was CZX. CMZ and LMOX were found to show relatively high MIC values for those species. Against S. aureus, CEZ showed the best antibacterial activity, but 3 resistant strains had MICs of greater than 100 micrograms/ml. 4. With regard to Gram-negative bacteria, CTX and CZX showed the best antibacterial activities for all of the species, except for P. aeruginosa. These were followed, in order, by LMOX and CPZ. Compared with these 4 antibiotics, CTM, CMZ and CEZ were found to have inferior antibacterial activities against these bacteria. In relation to P. aeruginosa, the peak of the MIC distribution for CPZ was 6.25 micrograms/ml, and this was the best antibacterial activity detected with the various antibiotics tested. This was followed by CTX (25 micrograms/ml) LMOX (25 micrograms/ml) and CZX (50 micrograms/ml). CTM had an MIC of 100 micrograms/ml for 1 strain, and MICs of greater than 100 micrograms/ml for all of the other strains of P. aeruginosa, indicating them to be resistant to this antibiotic. All of the strains were resistant to CMZ and CEZ, showing MICs of greater than 100 micrograms/ml. 5. For each of the tested antibiotics, no correlation was found between the MIC and the serogroup for either P. aeruginosa or S. marcescens.

[Clinical significance of the measurement of serum pepsinogen group I and II by enzyme-linked immunosorbent assay].

We have developed enzyme-linked immunosorbent assay (ELISA) for pepsinogen group I and II (PG I.II) in human serum, and clinical significance of serum pepsinogen measurement was evaluated. Serum PG I.II levels in patients with gastric and duodenal ulcer were higher than those in normal healthy subjects. On the other hand, serum PG I levels in patients with pernicious anemia were significantly low levels. In both gastric ulcer and duodenal ulcer, serum PG I.II levels at active stage were higher than healing stage. These results suggested that the measurement of PG I.II levels was useful for screening or monitoring test for the injury of gastric and duodenal mucosa.

[Newly developed detection system for serum Helicobacter pylori antibodies using ELISA and its clinical significance].

Using ELISA, a specific and sensitive system that detects serum immunoglobulin G antibodies against all soluble antigens of Helicobacter pylori (Hp) has been developed. This system is used at three different concentrations of Hp antigens coated on the solid phase of the ELISA. Anti-Hp antibodies were judged positive when the difference in the ELISA values between high and middle or middle and low concentrations of antigen were over the specific values. For the ELISA system, called the three point antigen method, sensitivity and specificity of urease activity were 86.9% and 70.8%, respectively. Positive rate for antibodies to serum Helicobacter pylori in dyspeptic patients was higher than that in healthy subjects.