Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande.

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.

Search for Nucleon and Dinucleon Decays with an Invisible Particle and a Charged Lepton in the Final State at the Super-Kamiokande Experiment.

Search results for nucleon decays p→e^{+}X, p→µ^{+}X, n→νγ (where X is an invisible, massless particle) as well as dinucleon decays np→e^{+}ν, np→µ^{+}ν, and np→τ^{+}ν in the Super-Kamiokande experiment are presented. Using single-ring data from an exposure of 273.4 kton·yr, a search for these decays yields a result consistent with no signal. Accordingly, lower limits on the partial lifetimes of τ_{p→e^{+}X}>7.9×10^{32} yr, τ_{p→µ^{+}X}>4.1×10^{32} yr, τ_{n→νγ}>5.5×10^{32} yr, τ_{np→e^{+}ν}>2.6×10^{32} yr, τ_{np→µ^{+}ν}>2.2×10^{32} yr, and τ_{np→τ^{+}ν}>2.9×10^{31} yr at a 90% confidence level are obtained. Some of these searches are novel.

Search for neutrinos from annihilation of captured low-mass dark matter particles in the sun by super-kamiokande.

Super-Kamiokande (SK) can search for weakly interacting massive particles (WIMPs) by detecting neutrinos produced from WIMP annihilations occurring inside the Sun. In this analysis, we include neutrino events with interaction vertices in the detector in addition to upward-going muons produced in the surrounding rock. Compared to the previous result, which used the upward-going muons only, the signal acceptances for light (few-GeV/c^{2}-200-GeV/c^{2}) WIMPs are significantly increased. We fit 3903 days of SK data to search for the contribution of neutrinos from WIMP annihilation in the Sun. We found no significant excess over expected atmospheric-neutrino background and the result is interpreted in terms of upper limits on WIMP-nucleon elastic scattering cross sections under different assumptions about the annihilation channel. We set the current best limits on the spin-dependent WIMP-proton cross section for WIMP masses below 200 GeV/c^{2} (at 10 GeV/c^{2}, 1.49×10^{-39} cm^{2} for χχ→bb[over ¯] and 1.31×10^{-40} cm^{2} for χχ→τ^{+}τ^{-} annihilation channels), also ruling out some fraction of WIMP candidates with spin-independent coupling in the few-GeV/c^{2} mass range.

Search for trilepton nucleon decay via p→e+νν and p→µ+νν in the Super-Kamiokande experiment.

The trilepton nucleon decay modes p→e+νν and p→µ+νν violate |Δ(B-L)| by two units. Using data from a 273.4 kt yr exposure of Super-Kamiokande a search for these decays yields a fit consistent with no signal. Accordingly, lower limits on the partial lifetimes of τp→e+νν>1.7×10(32) years and τp→µ+νν>2.2×10(32) years at a 90% confidence level are obtained. These limits can constrain Grand Unified Theories which allow for such processes.

First indication of terrestrial matter effects on solar neutrino oscillation.

We report an indication that the elastic scattering rate of solar B8 neutrinos with electrons in the Super-Kamiokande detector is larger when the neutrinos pass through Earth during nighttime. We determine the day-night asymmetry, defined as the difference of the average day rate and average night rate divided by the average of those two rates, to be [-3.2 ± 1.1(stat) ± 0.5(syst)]%, which deviates from zero by 2.7 σ. Since the elastic scattering process is mostly sensitive to electron-flavored solar neutrinos, a nonzero day-night asymmetry implies that the flavor oscillations of solar neutrinos are affected by the presence of matter within the neutrinos' flight path. Super-Kamiokande's day-night asymmetry is consistent with neutrino oscillations for 4 × 10(-5) eV(2) ≤ Δm 2(21) ≤ 7 × 10(-5) eV(2) and large mixing values of θ12, at the 68% C.L.

Randomized, double-blind, crossover, placebo-controlled clinical trial to evaluate the effects of chicken hot water extract on insulin secretion.

OBJECTIVE: Essence of chicken (EOC), a hot water extract of chicken, is widely consumed in Southeast Asia as a beverage. EOC has an inhibitory effect on the elevation of blood glucose levels and a secretagogue effect on insulin. However, the mechanism by which EOC promotes insulin secretion is unknown. We aimed to verify the postprandial hyperglycemic inhibitory effect and the insulin secretory effect of EOC in healthy adults under appropriate placebo settings. In addition, we aimed to understand the mechanism underlying the insulin secretory effect of EOC. PATIENTS AND METHODS: Thirty-four healthy Japanese adults were fed 68 mL of EOC or control food, followed by 200 g of cooked rice. Blood glucose and plasma insulin levels were measured at 30, 45, 60, 90, and 120 min after the participants ate cooked rice. The trial had a randomized, double-blind, crossover, placebo-controlled design. RESULTS: The ingestion of EOC induced an increase in the maximum blood concentration (Cmax) of insulin and shortened the time required to reach the maximum blood concentration following rice consumption. Ingestion of the test beverage resulted in a significantly higher insulinogenic index than that obtained after ingestion of the control beverage. No side effects were observed in this study. Mechanistic experiments revealed that EOC stimulated significant (p < 0.05) secretion of GLP-1 from NCI-H716 human intestinal L cells at 0.1, 1, and 10 mg/mL. CONCLUSIONS: Consuming EOC when eating rice supports pancreatic function. Daily consumption of EOC could elevate the early-phase insulin response; therefore, it could prevent diabetes in Asians with low insulin secretion.

Endonuclease activity on damaged DNA in rat regenerating liver.

The activity of an endonuclease(s) acting on double-stranded, ultraviolet-irradiated, and 2-acetylaminofluorene-bound DNA but not on double-stranded undamaged DNA triples within two hr after partial hepatectomy. Although the activity drops between four and six hr after operation, it remains above levels measured in livers of nonhepatectomized rats until 36 hr after operation. Between 36 and 48 hr after operation, the enzyme activity drops below the levels in liver of nonhepatectomized rats and then rises slowly to reach levels observed in nonhepatectomized animals between 48 hr and seven days after the operation. Studies on the effect of actinomycin on the activity of crude enzyme and on the incorporation of [14C]leucine and [14C]valine on the purified enzyme indicate that the increase in enzyme activity results from de novo synthesis. Eight % of endonucleolytic activity detectable in the crude homogenate is inhibited by an hyperimmune serum prepared against the purified enzyme. By adjusting the time of injection of 2-[14C]acetylaminofluorene with respect to the levels of enzyme activity after partial hepatectomy, an inverse correlation between binding and enzyme activity was demonstrated.

The effect of a mammalian repair endonuclease on x-irradiated DNA.

DNA was extracted from rat liver of non-irradiated animals, and was irradiated in vitro, and from animals which received whole body doses of X-radiation. Sedimentation on neutral and alkaline sucrose gradients as well as measurements of 32P release after sequential treatment with endonuclease and alkaline phosphatase and determination of triphosphate incorporation after the sequential treatment with endonuclease, alkaline phosphatase and DNA polymerase indicated that DNA irradiated in vivo and in vitro were effective substrates for the mammalian repair endonuclease. The experiments suggest that in addition to strand breaks, X-radiation causes base damage and they have provided a plausible explanation for the formation of double strand breaks in DNA irradiated in vivo.

Induction of manganese superoxide dismutase by thyroid stimulating hormone in rat thyroid cells.

Alterations in the superoxide dismutase (SOD) content of thyroid tissues occurring in association with thyroid dysfunction have been reported. In this study, the Mn-SOD content was found to increase in thyroid tissues of rats administered thyroid stimulating hormone (TSH) and in thyrocytes cultured in medium supplemented with TSH. Furthermore, in the thyroid glands of rats whose serum TSH level was elevated by inhibiting the synthesis of T3 and T4 by 6-methyl-2-thiouracil, the Mn-SOD increased as the TSH concentration increased. In the cultured thyrocytes, the increase in Mn-SOD induced by TSH was inhibited by the C-kinase inhibitor H7. These findings suggest the induction of Mn-SOD by TSH in thyroid cells and point to a role of C-kinase in this process, thereby indicating that a close relationship exists between the serum TSH level and the change in Mn-SOD content in thyrocytes with thyroid dysfunction.

Preparation of soluble recombinant T cell receptor alpha chain by using a calmodulin fusion expression system.

We have isolated a full length T cell receptor alpha chain (TCR alpha) cDNA derived from a bee venom phospholipase A2-specific mouse suppressor T cell hybridoma. A bacterial fusion expression system was constructed using rat calmodulin as a fusion partner for production of soluble TCR alpha. In this system, calmodulin-TCR alpha fusion protein was expressed at a high level in the soluble fraction of bacterial cell lysate, and could be purified by binding of calmodulin portion of the protein to phenyl-Sepharose. Using this system, fusion proteins containing a TCR alpha peptide corresponding to the complete extracellular region, V alpha-J alpha region or C alpha extracellular region were isolated. TCR alpha peptides were then released from the fusion proteins by digestion with thrombin which recognizes a linker sequence between calmodulin portion and TCR alpha segment. Polyclonal antibodies against constant region of TCR alpha chain (C alpha) were obtained by immunization of rabbits with the recombinant C alpha peptide. ELISA for TCR protein was established by using the polyclonal antibodies and the monoclonal antibody specific for C alpha region.

Decrease of endothelial nitric oxide synthase in stroke-prone spontaneously hypertensive rat cerebral cortex.

We reported in our previous study that constitutive nitric oxide synthase (cNOS) activity significantly decreased and oxygen stress increased in the 31-week-old stroke-prone spontaneously hypertensive rat (SHRSP) cerebral cortex (CC). In the present study we examined the protein amount of two cNOS isoforms, the neuronal and the endothelial types, in SHRSP CC using Western blot analysis. Although no significant difference was observed in the amount of neuronal NOS (nNOS) protein, endothelial NOS (eNOS) protein prominently decreased in 31-week-old SHRSP CC compared to age-matched Wistar Kyoto rat and 15-week-old SHRSP. In rats at this age, we also observed a large quantity of albumin in the protein amount. However, the protein amount of heat shock protein 70, which is a molecular chaperon and a marker of injury, showed no significant changes. These results indicate that the alteration of eNOS but not of nNOS protein would be more closely associated with the development of stroke in SHRSP.

Age-related change of antioxidant capacities in the cerebral cortex and hippocampus of stroke-prone spontaneously hypertensive rats.

Regional distribution and age-related change of Mn-, Cu/Zn-superoxide dismutase (SOD) and constitutive type of nitric oxide synthase (NOS) activities in the brain were determined using stroke-prone spontaneously hypertensive rats (SHRSP). In the hippocampus (HIP), Mn- and Cu/Zn-SOD activities in SHRSP of 31-week-old were significantly lower than those of 15-week-old or normotensive rats (WKY). From Mn-SOD immunohistochemical staining of several subfields of the HIP, our results suggested that SHRSP hippocampal CA1 was more vulnerable to oxidative stress compared with WKY and other subfields. In the 31-week-old SHRSP cerebral cortex (CC), the activities of Mn-, Cu/Zn-SOD and NOS were significantly lower than those in WKY. At this age, most of the SHRSP developed cerebral injuries. These observations indicated that hypertensive vascular disease observed in the SHRSP CC resulted from the decreased antioxidant capacity that is closely associated with the development of stroke and, in turn, shortened life span.

The action of a mammalian endonuclease on psoralen-bound DNA.

The sequential actions of two enzymes believed to be involved in DNA repair, namely a mammalian endonuclease and the bacterial DNA polymerase I on psoralen bound 32P-labeled DNA, was studied. When ultraviolet-irradiated DNA is exposed to the sequential action of the endonuclease, the formation of single-strand breaks prepares the DNA for the exonucleolytic excision of thymine dimers. The mammalian endonuclease purified from rat liver to electrophoretic homogeneity is inactive on normal DNA, DNA irradiated at 360 nm or DNA mixed with psoralen without irradiation. Incubation of psoralen-bound DNA labeled with 32P with the endonuclease releases the isotope in the acid soluble indicating that psoralen-bound DNA is susceptible to the endonucleolytic attack. Sedimentation of DNA on sucrose gradients indicates that there is no collapse of the DNA molecule after treatment with the endonuclease. Moreover, there is no release of the adduct in the acid soluble after treatment with DNA polymerase, indicating that the 5--3 min exonucleolytic activity of that enzyme is impaired by the remaining crosslinks. The crosslinks also inhibit the incorporation of [3H] dATP in presence of DNA polymerase I.

Morphological and functional differentiation of human thyroid cells in collagen gel culture.

OBJECTIVE: Cultured human thyroid cells in collagen gel culture were examined on cell morphology and the production of thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4) which are components of functional differentiation. METHODS: Thyroid cells obtained from normal human thyroid tissues (four cases), follicular adenoma tissues (three cases), papillary carcinoma tissues (three cases), and follicular carcinoma tissue (one case), were cultured in collagen gel. Then these cultured cells were observed on cellular morphology and production of Tg, T3 and T4. Moreover, changes in morphological characteristics and production of Tg, T3 and T4 induced by addition of thyroid stimulating hormone (TSH) and epidermal growth factor (EGF) to medium in collagen gel culture were determined. RESULTS: Normal and tumor cells in collagen gel culture formed colonies and follicles with Tg production, similar to in vivo-like three-dimensional cellular structures and functions. Normal thyroid cells stimulated TSH induced more Tg and produced morphological changes, i.e. enlarged follicular lumens and increased the height of follicular cells, but did not promote cell proliferation. Reversely, normal thyroid cells stimulated with EGF promoted cell proliferation, but did not change morphological findings and did not increase production of Tg, T3 and T4. CONCLUSIONS: These findings suggest that collagen gel culture is useful for observing the effects of stimulation by cell growth factor on the morphological and functional differentiation of human thyroid cells.

Productivity of thyroglobulin and thyroid hormone on human thyroid cell in collagen gel culture.

Thyroid cells obtained from 21 normal human thyroid tissue samples and 17 tissue samples from diseased thyroid, including one of Graves disease, 4 with follicular adenoma, 11 with papillary carcinoma, and 1 with follicular carcinoma, were cultured in collagen gel, and ability to produce thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4) was determined. Changes in morphological characteristics and production of Tg, T3, and T4 induced by addition of thyroid stimulating hormone (TSH) to medium in collagen gel culture were also determined. Twenty of all cases exhibited positive reaction for Tg. No relationship was found between rate of positivity for Tg and pathologic diagnosis. Three with carcinoma showed positive reaction for T3, and 4 with carcinoma showed positive reaction for T4. Only for normal thyroid cells did addition of TSH to medium induce increase the percentage of colonies producing Tg or T4 and morphological changes including an enlarged follicular lumen and increase in the height of columnar epithelium. These findings suggest that thyroid cells in collagen culture develop in an in vivo-like fashion. In conclusion, collagen has important effects on cellular differentiation when included in extracellular matrix.

Type IV collagenase and immunostaining of type IV collagen in human thyroid tumors.

OBJECTIVE: Required stages in the processes of malignant tumor invasion and metastasis are known to include the destruction of cell stroma and vascular basement membrane. It has been suggested that type IV collagenase can degrade type IV collagen, a main component of basement membrane. In our study, type IV collagenase activity was compared with the grade of destruction of type IV collagen by thyroid tumors. METHODS: Type IV collagenase activity was measured in human thyroid tissue obtained surgically from four patients with Graves' disease, four with follicular adenoma, six with papillary carcinoma, and four with follicular carcinoma. Six normal thyroid tissue specimens were also studied. The grade of destruction in the diseased regions of thyroid tumors and surrounding intact tissues were determined immunochemically by anti-type IV collagen antibody staining. RESULTS: Tumors with high type IV collagenase activity exhibited extracapsular invasion, lymph node metastasis and very weak discontinuity of immunostaining for type IV collagen from the basement membrane in diseased regions. In addition, surrounding intact tissues exhibited weak immunostaining for type IV collagen. Tumors with low type IV collagenase activity exhibited neither extracapsular invasion nor lymph node metastasis, but did exhibit weak immunostaining for type IV collagen from the basement membranes in diseased regions. However, the surrounding intact tissues had preserved type IV collagen in follicular basement membranes. CONCLUSION: These findings suggest that staining for type IV collagen can be considered a biochemical marker for prediction of the aggressiveness of invasion and metastasis.

Study on cathepsin B activity in human thyroid tumors.

Cathepsin B activity was measured in human thyroid tissue obtained surgically from 2 patients with Grave's disease, 3 with follicular adenoma, 4 with papillary carcinoma, and 4 with follicular carcinoma. Three normal thyroid tissues were also studied. Comparisons were made between cathepsin B activity and clinical findings, including histopathological diagnosis and the presence or absence of extra-capsular invasion and metastasis. The abilities of original tumors to degrade type I and type IV collagen were also measured. Mean cathepsin B activities of both specimens with benign and those with malignant disease were significantly higher than those of normal thyroid. On cases of thyroid carcinoma, those with extra-capsular invasions and metastasis had the highest cathepsin B activities. Cases with high cathepsin B activities also tended to show high type I and IV collagen degrading abilities. These findings suggest that cathepsin B plays a role in the development of extra-capsular invasion and lymph node metastasis in human thyroid tumors.

Malignancies of human thyroid tumors and dynamic magnetic resonance imaging (MRI).

Time intensity curves for gadolinium-diethylene triaminepentacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI), namely dynamic MRI, were determined for thyroid diseases and compared with findings of histopathologic examination. Time intensity curves for solid lesions were determined, excluding cases with secondary changes such as calcification, hemorrhage, necrosis and fibrosis. Three different patterns of time intensity curves were observed: rapid washout, delayed washout and no change. In our previous study, malignant grades of thyroid tumors were estimated immunohistochemically by epidermal growth factor receptor (EGFR) antibody. In most of malignant diseases and a few benign diseases that had marked cell proliferative activity with staining EGFR strongly, the time intensity curve displayed a delayed washout pattern, in which intensity was above 1/2-maximal value within 10 min after injection Gd-DTPA. Almost all benign diseases and a few well differentiated carcinomas displayed a rapid washout pastern, in which intensity was decreased to lower than 1/2 of peak grade within 10 min following injection and showed staining EGFR weakly. Benign diseases showing no change of time intensity curve, did not almost show aEGFR positive cell. These findings suggested that the time intensity curve obtained from dynamic MRI might indicate differentiated grades and cell proliferating activity of thyroid tumors.

Appearance of peculiar vessels with immunohistological features of high endothelial venules in the dermis of moxibustion-stimulated rat skin.

Morphological changes of the dermal blood vessels ofmoxibustion-stimulated rat skin were examined with reference to the lymphocyte migration. After long-term stimulation with direct moxibustion to the acupoint tsu-san-li (St-36), peculiar vessels that possess immunohistological features of high endothelial venules could be observed in the moxa-stimulated acupoint dermis. Endothelial cells of the vessels had well-developed Golgi apparatus in their plump cytoplasms, and they strongly expressed intercellular adhesion molecule-1 on the luminal surface. These data suggest that the appearance of the peculiar vessels in the dermis acts toward the active infiltration of blood-lymphocytes into the acupoint skin.

[Studies on early changes in myocardial electrolytes and histological reaction in isoproterenol-induced myocardial injury].

To determine morphological changes in the very early stage of damage and recovery of myocardial fibers in relation to electrolytes and water content in the myocardium, experimental myocardial infarcts were produced after injection of 75 mg/kg isoproterenol (Isp) to rats weighing 270 +/- 10 g. Electrolytes were examined by an atomic absorption spectrophotometer, and histologic examination was performed by light and electron microscopy. At 30 min after Isp injection, Ca and water contents of myocardium increased, but Mg decreased. These myocardial damages showed a maximum level from 6 to 12 h after injection of Isp. It consisted of reversible injury of muscle fibers represented by eosinophilic and fatty degeneration, intermingled with coagulation necrosis of fibers which was irreversible. Most of these eosinophilic degeneration fibers recovered to normal fibers between 12 h and 3 d after the injection. The chronological changes of Ca, Mg, and water contents were well correlated to the morphological early changes of myocardial fibers, and this experimental model by using Isp may be useful for examining the recovery of damaged myocardial tissue and estimating the effects of therapeutics.