Colchicine protects against cartilage degeneration by inhibiting MMP13 expression via PLC-γ1 phosphorylation.

OBJECTIVE: Low molecular weight compounds that reduce the expression of MMP13 at the mRNA level might serve as disease-modifying osteoarthritis (OA) drugs (DMOADs). The objective of this study was to identify a candidate DMOAD that targets MMP13 expression. DESIGN: High-throughput screening was performed to identify compounds that suppress inflammatory cytokine-induced MMP13 expression. Ingenuity pathway analysis (IPA) using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis was conducted to identify signaling pathways related to cytokines. MMP13 expression in chondrocytes was evaluated through RT-qPCR and western blotting analyses. Additionally, 10-week-old mice were subjected to destabilization of the medial meniscus (DMM) surgery to induce OA and were sacrificed 12 weeks post-surgery for pathological examination. OA was evaluated using the OARSI scoring system. RESULTS: Colchicine was identified as a DMOAD candidate as it inhibited inflammatory cytokine-induced MMP13 expression in vitro, and the colchicine-administered mice with DMM presented significantly lower OARSI scores (adjusted P: 0.0242, mean difference: 1.6, 95% confidence interval (CI) of difference: 0.1651-3.035) and significantly lower synovial membrane inflammation scores (adjusted P: 0.0243, mean difference: 0.6, 95% CI of difference: 0.06158-1.138) than mice with DMM. IPA further revealed that components of the Rho signaling pathways are regulated by cytokines and colchicine. IL-1ß and TNF-α activate RAC1 and SRC signals, respectively, leading to the phosphorylation of PLC-γ1 and synergistic induction of MMP13 expression. Most notably, colchicine abrogates inflammatory cytokine-induced phosphorylation of PLC-γ1, leading to the induction of MMP13 expression. CONCLUSIONS: Colchicine is a potential DMOAD candidate that inhibits MMP13 expression and consequent cartilage degradation by disrupting the SRC/RAC1-phospho-PLCγ1-Ca2+ signaling pathway.

Eriodictyon angustifolium extract, but not Eriodictyon californicum extract, reduces human hair greying.

OBJECTIVE: Yerba Santa (Eriodictyon angustifolium and Eriodictyon californicum) has been used for many years in traditional medicine. However, the effect of Yerba Santa on melanogenesis has not yet been investigated. We aimed to assess the biological effects of Yerba Santa on hair pigmentation. METHODS: Yerba Santa extracts were assessed for their cytological effects following X-ray irradiation treatment and then tested directly for the prevention of human hair greying. Ultra-performance liquid chromatography (UPLC) was utilized to identify the individual extract components. RESULTS: Eriodictyon angustifolium extract significantly increased melanin synthesis in the melanoma cell line through activation of the WNT/MITF/tyrosinase-signalling pathway. In contrast, E. californicum had no effect on melanin synthesis. E. angustifolium extract also demonstrated a protective effect against the damage induced by X-ray irradiation in human keratinocytes. Application of the extracts to subjects who had grey beards demonstrated a reduced number of grey beard hair per year specifically with the E. angustifolium extract. A significant decrease in grey head hair was also observed after application of E. angustifolium extract. Upregulation of gene expression related to melanin production and WNT signalling was observed after the application of E. angustifolium extract. Sterubin was the most abundant flavonoid detected by UPLC in E. angustifolium extract. In addition, sterubin showed the highest difference in terms of quantity, between E. angustifolium and E. californicum extract. CONCLUSION: Eriodictyon angustifolium extract, which is abundant in sterubin, may be suitable as a potential cosmetic and medical agent for the prevention and improvement of hair greying.

OBJECTIF: Yerba Santa (Eriodictyon angustifolium et Eriodictyon californicum) est utilisé depuis de nombreuses années en médecine traditionnelle. Cependant, l'effet de Yerba Santa sur la mélanogenèse n'a pas encore été étudié. Notre objectif était d'évaluer les effets biologiques de Yerba Santa sur la pigmentation des cheveux. MÉTHODES: Les extraits de Yerba Santa ont été évalués pour leurs effets cytologiques après un traitement d'irradiation aux rayons X, puis testés directement pour la prévention du grisonnement des cheveux humains. La chromatographie liquide ultra-performante (UPLC) a été utilisée pour identifier les composants d'extrait individuels. RÉSULTATS: L'extrait d'E. angustifolium a augmenté de manière significative la synthèse de mélanine dans la lignée cellulaire du mélanome par l'activation de la voie de signalisation WNT/MITF/tyrosinase. En revanche, E. californicum n'a eu aucun effet sur la synthèse de mélanine. L'extrait d'E. angustifolium a également démontré un effet protecteur contre les dommages induits par l'irradiation aux rayons X dans les kératinocytes humains. L'application des extraits à des sujets qui avaient une barbe grise a démontré un nombre réduit de poils gris par an spécifiquement avec l'extrait d'E. angustifolium. Une diminution significative des cheveux gris a également été observée après l'application d'extrait d'E. angustifolium. Une régulation à la hausse de l'expression des gènes liée à la production de mélanine et à la signalisation WNT a été observée après l'application d'extrait d'E. angustifolium. La stérubine était le flavonoïde le plus abondant détecté par UPLC dans l'extrait d'E. angustifolium. De plus, la stérubine a montré la plus grande différence en termes de quantité entre E. angustifolium et E. californicum. CONCLUSION: L'extrait d'E. angustifolium, qui est abondant en stérubine, peut convenir comme agent cosmétique et médical potentiel pour la prévention et l'amélioration du grisonnement des cheveux.

Effective countermeasures for Salmonella contamination in actual oilmeal-manufacturing plant in India.

AIMS: Salmonella contamination in the manufacturing process of an overseas oilmeal plant was investigated and countermeasures for Salmonella contamination were evaluated. METHODS AND RESULTS: Salmonella was detected from deposits and adhered materials inside the main processing equipment. Specifically high contamination was observed in the equipment associated with the meal cooler, with several Salmonella serovars being detected. A number of Salmonella serovars were also detected in the equipment of the fine powder recovery process. To prevent Salmonella contamination of oilmeal products, effective countermeasures that have been employed in Japan were implemented. By removing residues from the equipment and disinfecting the interior of the equipment, a significant decrease in the contamination rate of oilmeal products was achieved compared to before sanitation (P < 0·05). CONCLUSIONS: Effective countermeasures to control Salmonella contamination in the overseas manufacturing process of oilmeal were established. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report focusing on Salmonella countermeasures in an actual oilmeal-manufacturing plant overseas.

Effect of the combined use of enamel matrix derivative and atelocollagen sponge scaffold on osteoblastic differentiation of mouse induced pluripotent stem cells in vitro.

BACKGROUND AND OBJECTIVE: Induced pluripotent stem cells (iPSCs) are a candidate cell source in periodontal regenerative therapy. Enamel matrix derivative (EMD) has been shown to regenerate periodontal tissues, and atelocollagen sponge (ACS) is considered a suitable scaffold or carrier for growth factors. This study aimed to investigate the effect of combined use of EMD and an ACS scaffold on cell behaviors and differentiation of mouse iPSCs (miPSCs) in vitro. MATERIAL AND METHODS: Following embryonic body formation from miPSCs, dissociated cells (miPS-EB-derived cells) were seeded onto ACS with or without EMD, and cultured in osteoblast differentiation medium. Scanning electron microscopy and histological analyses were used to assess cell morphology and infiltration within the ACS. Cell viability (metabolism) was determined using an MTS assay, and expression of mRNA of osteoblastic differentiation markers was assessed by quantitative RT -PCR. Alkaline phosphatase (ALP) staining intensity and activity were evaluated. Mineralization was assessed by von Kossa staining, and calcium content was quantitated using the methylxylenol blue method. RESULTS: By 24 hours after seeding, miPS-EB-derived cells in both the EMD and control groups had attached to and infiltrated the ACS scaffold. Scanning electron microscopy images revealed that by day 14, many cytoplasmic protrusions and extracellular deposits, suggestive of calcified matrix, were present in the EMD group. There was a time-dependent increase in cell viability up to day 3, but no difference between groups was observed at any time point. The levels expressed of ALP and osterix genes were significantly higher in the EMD group than in the control group. Expression of runt-related transcription factor 2 was increased in the EMD group compared with the control group on day 7. EMD upregulated the expression of bone sialoprotein and osteopontin on day 14, whereas expression of osteocalcin was lower at all time points. The staining intensity and activity of ALP were higher in the EMD group than in the control group. Mineralization levels and calcium contents were significantly higher in the EMD group throughout the observation period. CONCLUSION: These data suggest that combining ACS with EMD increases levels of osteoblastic differentiation and mineralization in miPS-EB-derived cells, compared with ACS used alone.

Severe musculoskeletal time-loss injuries and symptoms of common mental disorders in professional soccer: a longitudinal analysis of 12-month follow-up data.

PURPOSE: Psychological factors have shown to be predictors of injury in professional football. However, it seems that this is a two-way relationship, as severe musculoskeletal time-loss injuries have shown to be associated with the onset of symptoms of common mental disorders (CMD). There is no longitudinal study performed exploring this interaction between symptoms of CMD and injuries. The purpose of this study was to explore the interaction between severe musculoskeletal time-loss injuries and symptoms of CMD in professional football players over a 12-month period. METHODS: Players were recruited by their national players' unions in five European countries. Symptoms of CMD included in the study were related to distress, anxiety/depression, sleep disturbance and adverse alcohol use. RESULTS: A total of 384 professional football players were enrolled in the study, of whom 262 (68%) completed the 12-month follow-up period. The mean age of the participants at baseline was 27 ± 5 years, and they had played professional football for 8 ± 5 years on average. Symptoms of CMD at baseline were not associated with the onset of severe musculoskeletal time-loss injuries during the follow-up period with relative risks (and 95% CI) ranging from 0.6 (0.3-1.0) to 1.0 (0.5-2.2). In contrast, severe musculoskeletal time-loss injuries reported at baseline were associated with the onset of symptoms of CMD during the follow-up period with relative risks ranging from 1.8 (0.8-3.7) to 6.9 (4.0-11.9). CONCLUSION: No relationship was found between symptoms of CMD and the onset of severe musculoskeletal time-loss injuries. However, professional football players who suffered from severe musculoskeletal time-loss injuries are likely to develop subsequent symptoms of CMD. This study emphasizes the need for an interdisciplinary medical approach, which not only focuses on the physical but also on the mental health of professional football players. An early identification of players at risk of symptoms of CMD, such as those suffering from severe musculoskeletal injuries, creates the opportunity for an interdisciplinary clinical medical team to treat the players timely and adequately. LEVEL OF EVIDENCE: Prospective cohort study, Level II.

Factors associated with a positive willingness to practise oral health care in the future amongst oral healthcare and nursing students.

OBJECTIVES: The purpose of this study was to identify the weak points in the knowledge and attitudes of first-year oral health care and nursing students towards oral health care and to identify the factors associated with their positive willingness to practise oral health care after becoming a health professional in order to develop oral healthcare curricula. MATERIALS AND METHODS: The subjects were 88 first-year dental students (DSs), 64 dental hygiene students (DHSs) and 119 nursing students (NSs) enrolled in schools in Japan, as of April 2017. A questionnaire was distributed to subjects in each school to assess their knowledge and attitudes towards oral health care. RESULTS: Less than half knew that oral health care was also provided in cancer hospitals, hospices, acute care hospitals, maternity wards and psychiatric wards. Only 46.2% knew that oral health care was effective in the prevention of aspiration pneumonia. The level of knowledge and attitudes in NSs regarding oral health care were likely to be lowest amongst the student groups. Only NSs' high interest towards oral health care was associated with their positive willingness to practise oral health care in the future although oral health students' high perceptions and interest regarding oral health care were associated with the willingness. CONCLUSION: This study showed oral healthcare and nursing students' weak points regarding their attitudes and knowledge of oral health care at early stages. Oral health academic staff and professionals should develop effective oral healthcare curricula for oral healthcare students and help nursing staff develop a collaborative nursing oral healthcare curriculum to motivate nursing students.

Nitrogen balance in patients with hemiparetic stroke during the subacute rehabilitation phase.

BACKGROUND: In highly invasive diseases, metabolism commonly changes. Hypercatabolism is frequent in acute stroke, and nitrogen balance tends to be negative. However, there has been no study describing nitrogen balance in subacute and chronic stroke patients. The present study aimed to examine nitrogen balance in the subacute and chronic phases and to identify the factors related to it. METHODS: Nitrogen balance was calculated from the collected urine of 56 patients with subacute stroke [mean (SD) 53.8 (18.4) days post-stroke] who were admitted for rehabilitation for their first-ever ischaemic or nonsurgical haemorrhagic stroke. In the first experiment, their nitrogen balance was measured during the rehabilitation phase, and factors (type, severity of hemiparesis, activities of daily living, dysphagia and malnutrition status) related to it were evaluated. The second experiment was performed to describe the time course of nitrogen balance in 31 consecutive patients, with assessments made at admission and at discharge. RESULTS: Nitrogen balance was positive in all patients in the subacute phase. A significant difference was seen in nitrogen balance between high and low fat-free mass in male patients. In the chronic phase, nitrogen balance was positive in 96% of the patients. There was no significant difference in nitrogen balance between discharge and admission. CONCLUSIONS: In the subacute and chronic phases of stroke, it was confirmed that hypercatabolism had resolved and that intensive rehabilitation is possible in the convalescent period of stroke.

Terahertz Dynamics of a Topologically Protected State: Quantum Hall Effect Plateaus near the Cyclotron Resonance of a Two-Dimensional Electron Gas.

We measure the Hall conductivity of a two-dimensional electron gas formed at a GaAs/AlGaAs heterojunction in the terahertz regime close to the cyclotron resonance frequency using highly sensitive Faraday rotation measurements. The sample is electrically gated, allowing the electron density to be changed continuously by more than a factor of 3. We observe clear plateaulike and steplike features in the Faraday rotation angle vs electron density and magnetic field (Landau-level filling factor) even at fields or frequencies very close to cyclotron resonance absorption. These features are the high frequency manifestation of quantum Hall plateaus-a signature of topologically protected edge states. We observe both odd and even filling factor plateaus and explore the temperature dependence of these plateaus. Although dynamical scaling theory begins to break down in the frequency region of our measurements, we find good agreement with theory.

Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species.

OBJECTIVE: In ovarian cancer cases, recurrence after chemotherapy is frequently observed, suggesting the involvement of ovarian cancer stem-like cells (CSCs). The chemoresistance of ovarian clear cell carcinomas is particularly strong in comparison to other epithelial ovarian cancer subtypes. We investigated the relationship between a CSC marker, aldehyde dehydrogenase 1 (ALDH1), and clinical prognosis using ovarian clear cell carcinoma tissue samples. Furthermore, we investigated the antioxidant mechanism by which CSCs maintain a lower reactive oxygen species (ROS) level, which provides protection from chemotherapeutic agents. METHODS: Immunohistochemical staining was performed to examine the CSC markers (CD133, CD44, ALDH1) using ovarian clear cell carcinoma tissue samples (n=81). Clear cell carcinoma cell lines (KOC-7C, OVTOKO) are separated into the ALDH-high and ALDH-low populations by ALDEFLUOR assay and fluorescence-activated cell sorting (FACS). We compared the intracellular ROS level, mRNA level of the antioxidant enzymes and Nrf2 expression of the two populations. RESULTS: High ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Other markers are not related to clinical stage and prognosis. ALDH-high cells contained a lower ROS level than ALDH-low cells. Antioxidant enzymes were upregulated in ALDH-high cells. ALDH-high cells showed increased expression of Nrf2, a key transcriptional factor of the antioxidant system. CONCLUSIONS: ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemoresistance in ovarian clear cell carcinoma.

Reopening of ductus arteriosus in idiopathic premature constriction or closure of ductus arteriosus: A case series.

BACKGROUND: There is no consensus on managing pregnancy when the fetus is diagnosed with idiopathic premature constriction or closure of the ductus arteriosus (PCDA). Knowing whether the ductus reopens is valuable information for managing idiopathic PCDA. We conducted a case-series study to investigate the natural perinatal course of idiopathic PCDA and examined factors associated with ductal reopening. METHODS: We retrospectively collected information about the perinatal course and echocardiographic findings at our institution, which, on principle, does not determine delivery timing based on fetal echocardiographic results. We also examined perinatal factors related to the reopening of the ductus arteriosus. RESULTS: Thirteen cases of idiopathic PCDA were included in the analysis. The ductus reopened in 38% of cases. Among cases diagnosed in < 37 weeks of gestation, 71% reopened, which was confirmed seven days after diagnosis (interquartile range 4-7). Diagnosis earlier in gestation was associated with ductal reopening (p = 0.006). Two cases (15%) developed persistent pulmonary hypertension. No fetal hydrops or death occurred. CONCLUSIONS: The ductus is likely to reopen when prenatally diagnosed before 37 weeks gestation. There were no complications due to our pregnancy management policy. In idiopathic PCDA, especially if the prenatal diagnosis is made before 37 weeks of gestational age, continuing the pregnancy with careful monitoring of the fetus's well-being is recommended.

Temperature-dependent magnetotransport around ν=1/2 in ZnO heterostructures.

The sequence of prominent fractional quantum Hall states up to ν=5/11 around ν=1/2 in a high-mobility two-dimensional electron system confined at oxide heterointerface (ZnO) is analyzed in terms of the composite fermion model. The temperature dependence of R(xx) oscillations around ν=1/2 yields an estimation of the composite fermion effective mass, which increases linearly with the magnetic field. This mass is of similar value to an enhanced electron effective mass, which in itself arises from strong electron interaction. The energy gaps of fractional states and the temperature dependence of R(xx) at ν=1/2 point to large residual interactions between composite fermions.

Ferroelectric soft mode in a SrTiO3 thin film impulsively driven to the anharmonic regime using intense picosecond terahertz pulses.

The ferroelectric soft mode in a SrTiO(3) thin film was impulsively driven to a large amplitude using intense picosecond terahertz pulses. As the terahertz electric field increased, the soft-mode absorption peak exhibited blueshifting and spectral narrowing. A classical anharmonic oscillator model suggests that the induced displacement is comparable to that of the ferroelectric phase transition. The spectral narrowing indicates that the displacement exceeds that induced by any inhomogeneities in the film, demonstrating that the method can be used to explore intrinsic quartic anharmonicity.

Osteoarthritic changes in the knees of recently retired male professional footballers: a pilot study.

Background: Knee osteoarthritis (OA) is common amongst retired male professional footballers. There is limited understanding with respect to the interplay between imaging findings, clinical presentation and patient-reported outcome measures (PROMs) in retired professional footballers with knee OA. Objectives: This pilot study aimed to evaluate the extent of radiological and clinical knee OA in a cohort of retired male professional footballers, and to explore the relationship between these findings and knee-related PROMs. Methods: Fifteen retired male professional footballers underwent knee radiographs and were surveyed on their history of clinical OA, severe knee injury and previous knee surgery. The Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS) and the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) were used to assess health outcomes, such as level of function and pain. Results: Radiological knee OA was diagnosed in six out of 15 participants. Seven of the participants had a clinical diagnosis of knee OA. Evidence of clinical and radiological OA was present amongst four participants. Radiological knee OA and clinical OA was significantly associated with a history of severe knee injury and previous knee surgery. Low correlations (ρ<-0.40) were found between knee OA severity and knee-related PROMs. Moderate correlation (ρ=-0.65) was found between clinical knee OA and KOOS-SP. Conclusion: Clinical knee OA correlates with PROMs amongst retired professional footballers but radiological OA does not. Further studies are required to understand the relationship between imaging findings, clinical presentation and PROMs amongst retired professional footballers with knee OA.

Time evolution of collisionless shock in counterstreaming laser-produced plasmas.

We investigated the time evolution of a strong collisionless shock in counterstreaming plasmas produced using a high-power laser pulse. The counterstreaming plasmas were generated by irradiating a CH double-plane target with the laser. In self-emission streaked optical pyrometry data, steepening of the self-emission profile as the two-plasma interaction evolved indicated shock formation. The shock thickness was less than the mean free path of the counterstreaming ions. Two-dimensional snapshots of the self-emission and shadowgrams also showed very thin shock structures. The Mach numbers estimated from the flow velocity and the brightness temperatures are very high.

Myosin light chain kinase mediates sarcomere organization during cardiac hypertrophy in vitro.

During the development of hypertrophy, cardiac myocytes increase organization of the sarcomere, a highly ordered contractile unit in striated muscle cells. Several hypertrophic agonists, such as angiotensin II, phenylephrine, and endothelin-1, have been shown to promote the sarcomere organization. However, the signaling pathway, which links extracellular stimuli to sarcomere organization, has not been clearly demonstrated. Here, we demonstrate that myosin light chain kinase specifically mediates agonist-induced sarcomere organization during early hypertrophic response. Acute administration of a hypertrophic agonist, phenylephrine, or angiotensin II, causes phosphorylation of myosin light chain 2v both in cultured cardiac myocytes and in the adult heart in vivo. We also show that both sarcomere organization and myosin light chain 2v phosphorylation are dependent on the activation of Ca2+/calmodulin pathway, a known activator of myosin light chain kinase. These results define a new and specific role of myosin light chain kinase in cardiac myocytes, which may provide a rapid adaptive mechanism in response to hypertrophic stimuli.

Enhanced osteoblast and osteoclast responses to a thin film sputtered hydroxyapatite coating.

A sputtering technique followed by a low temperature hydrothermal treatment has been demonstrated to produce a dense-and-bioactive hydroxyapatite thin film coating. The purpose of the present study was to investigate osteoblast and osteoclast responses to the hydroxyapatite coated plates and titanium plates with similar roughness. Rat bone marrow stromal cells were cultured on these plates to induce osteoblasts. The cells showed a significantly enhanced proliferation on the hydroxyapatite surface, accompanied by increase of osteoblastic phenotypes. The co-cultured osteoclasts exhibited the significantly different cell number and morphology between the hydroxyapatite and the titanium surfaces. A series of osteoclast marker genes were more stimulated on the hydroxyapatite and thirty two percent of the hydroxyapatite surface area could be resorbed by osteoclasts. The thin film sputtered hydroxyapatite could provide a favorable surface for both osteoblast and osteoclast formation and their function, indicating its good osteoconductivity and biodegradability.

Changes of SM muscles after STG harvest.

Semimembranosus (SM) muscle as well as Semitendinosus-Gracilis (STG) tendon have the same role in knee flexion and tibial internal rotation. Because STG tendons are generally used for anterior cruciate ligament (ACL) reconstruction, some compensational changes in SM muscle might have been induced. The purpose of this study was to investigate the changes of SM muscle affected by harvesting STG tendons. 10 Wistar-strain male rats were divided into control (C) and STG-dissected (STG) groups. Left STG tendons including the distal half of muscle portions were dissected in group STG and only skin incision was performed in group C. 4 weeks after the treatments, fiber types classification and ultrastructural observations were performed. In group STG the decrease of type IIa (fast-twitch fiber with high oxidative capacity) was observed in deep layers of SM muscle (p<0.01). In ultrastructural observations, the increase in lipid droplets and mitochondria and the irregularity of Z disc were observed in deep layers. These morphological changes indicated that the mechanical loading might increase in SM muscle after harvesting of STG. Because of minor injuries in SM muscle, hamstring strength exercise at early stage of rehabilitation program should be carefully performed following ACL reconstruction using STG tendons in clinical practice.

Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. III. Amplification of a generation of tumor-specific killer T-lymphocyte activities by suppressor T-cell-depleted hapten-reactive T lymphocytes.

2,4.6-trinitrophenyl (TNP)-reactive T-cell activities were raised in mice by immunization with TNP-isologous mouse gamma globulin. After establishing that TNP-reactive T lymphocytes can serve as amplifier cells for induction of killer T lymphocytes in allogeneic system, we explored the possibility of this hapten-reactive T-cell system to amplify tumor-specific killer T-lymphocyte activity in the syngeneic system. We utlized relatively weak immunogenic syngeneic plasmacytoma X5563 in C3H/He mice. Analysis of the TNP-reactive T-cell activities revealed that such T lymphocytes express the biological functions of both major subtypes of regulatory T cells, namely suppressors and helpers, and that TNP-reactive suppressor and helper T lymphocytes, respectively, differ in their relative susceptibility to specific inactivation by TNP conjugates of the nonimmunogenic D-amino acid copolymer, D-glutamic acid, and D-lysine (D-GL). By taking advantage of the relative susceptibility-difference to TNP-D-GL, selective inactivation of TNP-reactive suppressor T cells was induced by appropriate treatment with TNP-D-GL, and the generation of TNP-reactive helper T-cell activity was amplified. The supplement of augmented TNP-reactive helper T-cell activity to the system at the immunization with syngeneic X5563 with TNP-haptenation, resulted in a striking augmentation of induction of tumor-specific killer T-lymphocyte activity, and a considerable number of hosts survived after the challenge with lethal dose of viable tumor cells. Thus, appropriate manipulations designed to induce potent hapten-reactive helper T-lymphocytes provided the potential for a very effective mode of immunoprophylaxis against tumor.

Optical Hall effect in the integer quantum Hall regime.

Optical Hall conductivity σ{xy}(ω) is measured from the Faraday rotation for a GaAs/AlGaAs heterojunction quantum Hall system in the terahertz-frequency regime. The Faraday rotation angle (∼ fine-structure constant ∼ mrad) is found to significantly deviate from the Drude-like behavior to exhibit a plateaulike structure around the Landau-level filling ν=2. The result, which fits with the behavior expected from the carrier localization effect in the ac regime, indicates that the plateau structure, although not quantized, still exists in the terahertz regime.

Electric-field-induced superconductivity in an insulator.

Electric field control of charge carrier density has long been a key technology to tune the physical properties of condensed matter, exploring the modern semiconductor industry. One of the big challenges is to increase the maximum attainable carrier density so that we can induce superconductivity in field-effect-transistor geometry. However, such experiments have so far been limited to modulation of the critical temperature in originally conducting samples because of dielectric breakdown. Here we report electric-field-induced superconductivity in an insulator by using an electric-double-layer gating in an organic electrolyte. Sheet carrier density was enhanced from zero to 10(14) cm(-2) by applying a gate voltage of up to 3.5 V to a pristine SrTiO(3) single-crystal channel. A two-dimensional superconducting state emerged below a critical temperature of 0.4 K, comparable to the maximum value for chemically doped bulk crystals, indicating this method as promising for searching for unprecedented superconducting states.