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Purpose: High resolution fMRI is a rapidly growing research field focused on capturing functional signal changes across cortical layers. However, the data acquisition is limited by low spatial frequency EPI artifacts; termed here as Fuzzy Ripples. These artifacts limit the practical applicability of acquisition protocols with higher spatial resolution, faster acquisition speed, and they challenge imaging in lower brain areas., Methods: We characterize Fuzzy Ripple artifacts across commonly used sequences and distinguish them from conventional EPI Nyquist ghosts, off-resonance effects, and GRAPPA artifacts. To investigate their origin, we employ dual polarity readouts., Results: Our findings indicate that Fuzzy Ripples are primarily caused by readout-specific imperfections in k-space trajectories, which can be exacerbated by inductive coupling between third-order shims and readout gradients. We also find that these artifacts can be mitigated through complex-valued averaging of dual polarity EPI or by disconnecting the third-order shim coils., Conclusion: The proposed mitigation strategies allow overcoming current limitations in layer-fMRI protocols: (1)Achieving resolutions beyond 0.8mm is feasible, and even at 3T, we achieved 0.53mm voxel functional connectivity mapping.(2)Sub-millimeter sampling acceleration can be increased to allow sub-second TRs and laminar whole brain protocols with up to GRAPPA 8.(3)Sub-millimeter fMRI is achievable in lower brain areas, including the cerebellum., Competing Interests: Conflict of interest: Omer Faruk Gulban is an employee of Brain Innovation (Maastricht, NL). The work presented here may be partly specific to industrial design choices of SIEMENS Healthineers’ UHF scanners. This vendor is used in 83% of all human layer-fMRI papers (source: www.layerfmri.com/papers).

To test the hypothesis that terrestrial runoff affects the functions of calcareous sediments in coral reefs and hampers the development of corals, we analysed calcareous sediments with different levels of bound phosphate, collected from reef areas of Okinawajima, Japan. We confirmed that phosphate bound to calcareous sediments was readily released into ambient seawater, resulting in much higher concentrations of phosphorous in seawater from heavily polluted areas (4.3-19.0 µM as compared with less than 0.096 µM in natural ambient seawater). Additionally, we examined the effect of phosphate released from calcareous sediments on the development of Acropora digitifera coral juveniles. We found that high phosphate concentrations in seawater clearly inhibit the skeletal formation of coral juveniles. Our results demonstrate that calcareous sediments in reef areas play a crucial role in mediating the impact of terrestrial runoff on corals by storing and releasing phosphate in seawater., (© 2021 The Authors.)

Background: Intravesical Bacillus Calmette-Guérin (BCG) is now a standard treatment for Ta, T1 carcinoma and carcinoma in situ (CIS) of the urinary bladder. In Japan, however, only BCG Tokyo 172 strain is commercially available. We therefore designed a clinical study of PMCJ-9 (BCG Connaught strain) for obtaining approval from Japanese Ministry of Health, Labor and Welfare., Methods: In the phase I-II study, PMCJ-9 40.5, 81 (standard dose overseas) or 121.5 mg in saline was instilled into the bladder of patients with Ta, T1 or CIS once weekly for 8 weeks. The recommended dose was decided and similarly administered in the late phase II study., Results: In the phase I-II study, 49 patients were evaluable for efficacy. The complete response (CR) rates were 60.0% (9/15), 68.2% (15/22) and 75.0% (9/12) in the 40.5, 81 and 121.5 mg groups. The incidence of adverse drug reactions (ADRs) was similar in all groups, but four 121.5 mg group patients developed severe ADRs. Thus, 81 mg was the recommended dose for the late phase II study. In that study, 39 patients were evaluable, showing CR rates of 71.8% (28/39) overall and 61.5% (16/26) and 92.3% (12/13) for the Ta, T1 and CIS cases. The safety was assessed in 42 patients and three (7.1%) were discontinued owing to ADRs., Conclusion: The recommended dose for the BCG Connaught strain was decided as 81 mg. PMCJ-9 administration at this dose level weekly for 8 weeks showed a clear antitumor effect and good safety profile against Ta, T1 and CIS transitional cell carcinoma of the bladder.

A highly sensitive and selective fluorometric determination method for ornithine and lysine has been developed. This method is based on an intramolecular excimer-forming fluorescence derivatization with a pyrene reagent, 4-(1-pyrene)butyric acid N-hydroxysuccinimide ester (PSE), followed by reversed-phase liquid chromatography (LC). The analytes, containing two amino moieties in a molecule, were converted to the corresponding dipyrene-labeled derivatives by reaction with PSE. The derivatives afforded intramolecular excimer fluorescence (450-550 nm) which can clearly be discriminated from the normal fluorescence (370-420 nm) emitted from PSE and monopyrene-labeled derivatives of monoamines. The structures of the derivatives and the emission of excimer fluorescence were confirmed by LC with mass spectrometry and with three-dimensional fluorescence detection system, respectively. The PSE derivatives of ornithine and lysine could be separated by reversed-phase LC on ODS column with isocratic elution. The detection limits (signal-to-noise ratio = 3) for ornithine and lysine were 3.5 and 3.7 fmol, respectively, for a 20-microl injection. Furthermore, this method had enough selectivity and sensitivity for the determination of ornithine and lysine in normal human urine.

A female F344 rat was injected with 2.4 x 10(6) MT-2 cells intravenously at 3 and 4 weeks old, and was mated with a non-infected male rat at the 17th week after injection, when the dam rat contained HTLV-1 provirus in the peripheral blood mononuclear cells as determined by polymerase chain reaction. HTLV-1 provirus was detected in at least 2 out of 9 offspring. This system should be useful for studies on the routes and prevention of vertical transmission and on elimination of once-transmitted HTLV-1.

The effect of pretreatment with antitumor drugs on lymphokine-activated killer (LAK) cell cytotoxic activity, determined by lactate-dehydrogenase(LDH)-release assay, was investigated. LAK cells were induced by incubating peripheral blood lymphocytes of healthy donors in medium containing interleukin-2 (IL-2) and monoclonal anti-CD3 antibody for 6-7 days. A human lung squamous carcinoma cell line, SQ-5, was used as an adherent target. After 24 h exposure of the target cells to cisplatin, doxorubicin, or mitomycin C, the drugs were washed off and LAK cells were added at an E/T ratio of 5. During further incubation for 48 h, LDH release from cisplatin- or doxorubicin-pretreated target cells was markedly higher than that from non-pretreated target cells. The combination of cisplatin and LAK cells has an additive cytotoxic effect and that of mitomycin C and LAK cells does not; there may also be an additive effect late in the toxicity mechanism between doxorubicin and LAK cells.

Cross-linking of effector T cells to target cancer cells augments their tumor lytic activities. Here we describe a new method of conjugating lymphokine-activated killer (LAK) cells with cancer-specific monoclonal antibody. The LAK cells were biotinylated, treated with avidin, and conjugated with biotinylated monoclonal antibody. These monoclonal antibody-conjugated LAK cells showed specifically enhanced killing activities against anti-tumor antibody-reactive cancer cells, and cold target cells specifically inhibited their activities.

The hst-1 gene, previously designated the hst gene, was identified as a transforming gene by transfection assays of genomic DNAs from various types of human cancers. We analyzed for alterations of the hst-1 gene in 18 bladder cancers, 23 renal cell carcinomas and 5 esophageal cancers. Although rearrangement of the gene was not detected in any of these samples, amplification of the hst-1 gene was found in 4 samples of tumors, including an invasive bladder cancer, both primary esophageal cancer and its lymph node metastasis, and kidney metastasis of an esophageal cancer. The same degree of amplification of the int-2 gene, the product of which has significant homology with the hst-1-encoded protein, was also observed in all of these DNA samples with amplified hst-1 gene. This result indicates close chromosomal localization of the two genes, which were amplified as one amplification unit.

Both the adenylate cyclase activity and the motility of human sperm were stimulated by bicarbonate with the same concentration dependency. The correlation between bicarbonate levels in semen and the motility of sperm from the patients with male infertility was investigated. Bicarbonate in semen was found to originate mainly from the seminal vesicles, and a significant positive correlation was observed between bicarbonate levels and volume of semen. The motility of infertile sperm was also found to correlate positively to the seminal levels of bicarbonate. These results suggest that the lowered levels of bicarbonate in semen are at least in part responsible for the poor sperm motility in infertile patients, as a result of the failure in the activation of sperm adenylate cyclase.

Fourteen kinds of trace elements were analyzed in the semen of 22 fertile men and 69 infertile men by means of inductively coupled plasma optical emission spectroscopy. Ca had the highest concentration, and the second and third highest concentrations were Zn and Mg, respectively. The concentrations of Ca, Cr, Mg, Pb, Sr, and Zn were almost the same between fertile and infertile men. Ni had a lower concentration in infertile than in fertile men. Many trace elements, such as Al, Cd, Cu, Mg, Mn, Mo, Sn, and Zn, had significantly higher concentrations in infertile men with normozoospermia than in fertile men. There was a significantly positive correlation between Zn and Mg levels in fertile and infertile men.

The detection and recording systems for urethral sounds during micturition were developed. This procedure was termed as "urophonography" and its recording as "urophonogram". Classification of urophonograms was undertaken on the basis of analyzing normal healthy male volunteers, and patients with benign prostatic hyperplasia. Four types of urophonogram were demonstrated. Urophonography was useful for investigation of dysfunctional voiding, and lower urinary tract obstruction. Urophonography will be a new approach to urodynamic investigations.