Non-tuberculosis Mycobacterial Pulmonary Disease Caused by Mycobacterium kiyosense, a New Species.

Non-tuberculosis mycobacterial (NTM) pulmonary disease (NTM-PD) is quite common, and newly identified species are being reported increasingly frequently thanks to advances in identification technologies. A 56-year-old woman had mild sputum production showed bronchiectasis with multiple small nodules, consistent with NTM-PD, on chest computed tomography. Mycobacterial species were isolated from the specimens; however, conventional methods could not identify the species. We conducted whole-genome sequencing and identified the NTM isolates as Mycobacterium kiyosense, a species newly registered in 2023 from Japan. She was diagnosed with NTM-PD caused by M. kiyosense and received watchful waiting.

Effect of Globin Digests on Physical Fatigue in Mice.

Globin digest (GD) inhibits dietary hypertriglyceridemia; however, its effects on physical fatigue remain unknown. Therefore, this study aimed to investigate the potential anti-fatigue effects of GD. Repeated administration of GD and valine (Val)-Val-tyrosine (Tyr)-proline (Pro), a component of GD, for five days prevented the forced walking-induced decrease in locomotion. Furthermore, GD treatment reversed the forced walking-induced increase in blood lactate levels in mice and increased phosphorylated AMP-activated protein kinase (p-AMPK) in the soleus muscle, suggesting that the anti-fatigue effect of GD involves AMPK activation in the soleus muscle through reduced blood lactate.

Urinary Retention Suggesting Aseptic Meningitis: Meningitis-Retention Syndrome Without Physical Signs of Meningeal Irritation.

Meningitis-retention syndrome (MRS) is the combination of aseptic meningitis and acute urinary retention that occurs in the absence of other neurological diseases. The cause(s) of MRS remain unclear. A 57-year-old Japanese woman was referred to our hospital for the evaluation of persistent fever and headache. The fever's cause was initially unclear, but the presence of urinary retention raised concern about possible aseptic meningitis despite no physical indications of meningeal irritation. Only typical cases of MRS have been reported thus far to our knowledge, and it is important that clinicians are aware of MRS when it presents in this atypical form.

Two cases of cartilaginous metaplasia in the sclera of Japanese White rabbits.

Spontaneous cartilaginous metaplasia of the sclera has not been reported in rabbits. Herein, we report two cases of spontaneous cartilaginous metaplasia in the sclera of Japanese White (JW) rabbits. Case 1 was noted in a 14-week-old male Kbs:JW rabbit that received a single ocular instillation of 20% isoproterenol (IP) a day before necropsy, and showed no abnormalities in clinical signs, ophthalmological assessments, and necropsy. Case 2 was noted in a 38-week-old male Kbs:JW rabbit that was housed under light-emitting diode (LED) lighting for 26 weeks and showed no effects of LED on clinical signs, ophthalmological assessments, and necropsy. Histological sections of the eyes of both animals were prepared and stained with hematoxylin and eosin (H&E) and Alcian blue, and immunohistochemical staining for vimentin was performed. The H&E-stained specimens showed focal hyaline cartilage-like tissues distributed between the scleral fibers at the posterior pole in both cases. The surrounding scleral fibers were compressed and/or partially destroyed by the cartilage-like tissue. The cartilage-like matrix was stained blue by Alcian blue, and immunohistochemistry showed that chondrocyte-like cells were positive for vimentin. Based on these findings, we diagnosed cartilaginous metaplasia in the sclera of Kbs:JW rabbits. The lesion was farther from the IP administration site in Case 1 and was not accompanied by other ophthalmological or histopathological abnormalities in either of the cases. This implies that the lesions occurred spontaneously owing to the abnormal differentiation of neural crest-derived cells.

Orbital malignant schwannoma and embryonal rhabdomyosarcoma in rats caused by leakage of locally injected nickel subsulfide to the orbit.

Nickel subsulfide (Ni3S2) is known to induce intraocular neoplasms when injected intravitreally into the eyes of rats. Here, we found two extraocular orbital neoplasms in two different rat strains, presumably due to the leakage of locally injected Ni3S2 to the extraocular orbital tissues. In the F344/DuCrlCrlj rat, an orbital mass arose at 30 weeks after injection, and invaded into the cranium. Histologically, the orbital mass was composed of areas arranged in parallel bundles formed by densely packed elongated or spindle-shaped cells with indistinct cytoplasmic borders, and of areas of hypocellular arrangement consisting of round cells in eosinophilic myxoid-like substances. Metastases were observed in the right submandibular and cervical lymph nodes. The neoplastic cells were immunopositive for S-100 protein and vimentin. Transmission electron microscopy revealed that the neoplastic cells had cellular processes and pericytoplasmic basal laminae. In the RccHanTM:WIST rat, an orbital mass arose at 36 weeks after injection. Histologically, the mass consisted of rhabdoid-like large round cells with proliferation of small round-to-polygonal cells, and these neoplastic cells infiltrated into the extraocular muscles. Immunohistochemically, the neoplastic cells were positive for desmin and vimentin. Transmission electron microscopy detected immature myofibrils with Z-band structures in the cytoplasm of these neoplastic cells. Consequently, the tumors were diagnosed as an orbital malignant schwannoma in an F344/DuCrlCrlj rat and an orbital embryonal rhabdomyosarcoma in a RccHanTM:WIST rat. The results of this case report suggest that leakage of Ni3S2 to the orbit caused the induction of orbital malignant schwannoma or rhabdomyosarcoma in rats.

Thin-Film Processing of Polypropylene and Polystyrene Sheets by a Continuous Wave CO2 Laser with the Cu Cooling Base.

Carbon dioxide (CO2) laser is widely used in commercial and industrial fields to process various materials including polymers, most of which have high absorptivity in infrared spectrum. Thin-film processing by the continuous wave (CW) laser is difficult since polymers are deformed and damaged by the residual heat. We developed the new method to make polypropylene (PP) and polystyrene (PS) sheets thin. The sheets are pressed to a Cu base by extracting air between the sheets and the base during laser processing. It realizes to cut the sheets to around 50 µm thick with less heat effects on the backside which are inevitable for thermal processing using the CW laser. It is considered that the boundary between the sheets and the base is in thermal equilibrium and the base prevents the sheets from deforming to support the backside. The method is applicable to practical use since it does not need any complex controls and is easy to install to an existing equipment with a minor change of the stage.

Dacomitinib as a retreatment for advanced non-small cell lung cancer patient with an uncommon EGFR mutation.

In non-small cell lung cancer (NSCLC), uncommon epidermal growth factor receptor (EGFR) mutations are mutations other than Ex19 deletion and Ex21 L858R, which are common mutations highly sensitive to EGFR-tyrosine kinase inhibitors. Afatinib, a second-generation EGFR-tyrosine kinase inhibitor, has been shown to be effective in patients with uncommon mutations. Dacomitinib, another second-generation EGFR-tyrosine kinase inhibitor, has not previously been shown to be effective in patients with uncommon mutations. Here, we report the efficacy of dacomitinib for uncommon EGFR mutations in a 71-year-old woman diagnosed with metastatic lung adenocarcinoma with uncommon EGFR mutation (Ex18 G719A). Afatinib was administered as the first-line treatment, and a remarkable antitumor effect was observed. However, the tumor grew after 14 months. Pemetrexed plus carboplatin followed by pemetrexed, docetaxel, atezolizumab and S-1 were performed in sequence. Although approximately four years had passed since the start of treatment, her physical condition was good. The patient started dacomitinib as the sixth-line treatment. Lesions were markedly reduced and treatment with dacomitinib was continued for 7.8 months. Dacomitinib is a possible treatment option for NSCLC with uncommon mutations.

Liver hydrolysate prevents depressive-like behavior in an animal model of colitis: Involvement of hippocampal neurogenesis via the AMPK/BDNF pathway.

Patients with inflammatory bowel disease (IBD) have higher rates of psychiatric pathology, including anxiety and depression. The dextran sulfate sodium (DSS)-treated mouse is a well-characterized animal model of colitis that exhibits IBD-like and depressive-like changes. A recent study found that phosphorylated (p-) adenosine monophosphate-activated protein kinase (AMPK) was associated with anti-inflammatory and antidepressant effects. Our previous research in an animal model of major depression suggests that liver hydrolysate (LH) has an antidepressant effect and combats physical fatigue by enhancement via the hippocampal or peripheral p-AMPK pathway. In this study, we examined whether or not LH has antidepressant and anti-inflammatory effects in mice with DSS-induced changes. We evaluated colon inflammation in DSS-treated mice and used the tail suspension and forced swimming tests to confirm whether or not LH prevents IBD-like symptoms and depressive-like behavior. Hippocampal expression of AMPK, brain-derived neurotrophic factor (BDNF), doublecortin, and neuronal nuclear antigen proteins was assessed by Western blotting. Hippocampal neurogenesis and morphometric changes in the microglia and astrocytes were examined by immunohistochemistry. DSS-treated mice showed IBD-like pathology and depressive-like behavior, a reduction in the hippocampal neuronal nuclear antigen level and neurogenesis, and increased hippocampal activation of microglia and astrocytes. These changes were reversed by LH. DSS-treated mice showed enhanced hippocampal expression of p-AMPK and BDNF after administration of LH. LH prevented depressive-like behavior by enhancing hippocampal neurogenesis through the AMPK/BDNF pathway and anti-neuroinflammation in the hippocampus. LH may be a therapeutic option for patients with IBD and depression.

Liver hydrolysate improves depressive-like behavior in olfactory bulbectomized mice: Involvement of hippocampal neurogenesis through the AMPK/BDNF/CREB pathway.

Recently, we has reported that AMPK activator has antidepressant effect. Previous our study suggested that liver hydrolysate (LH) activated adenosine monophosphate-activated protein kinase (AMPK) in periphery. However, the effect of LH on depression is unclear. Therefore, we examines whether LH has antidepressant effect on olfactory bulbectomized (OBX) mice. OBX mice showed depressive-like behavior in tail-suspension test and reduction of hippocampal neurogenesis, while these changes were reversed by LH. LH enhanced hippocampal phosphate-AMPK, brain-derived neurotrophic factor (BDNF) and phosphate-cyclic adenosine monophosphate response element-binding protein (CREB) in OBX mice. These data indicate that LH may produce antidepressant effects via hippocampal AMPK/BDNF/CREB signaling.

The Effect of Liver Hydrolysate on Chronic Ethanol-Induced Hepatic Injury in Normal Rats.

The mechanism underlying the improvement in hepatic function by liver hydrolysate (LH) after ethanol-induced hepatic injury is unclear. Therefore, we investigated the effects of LH administration on chronic ethanol-induced hepatic injury in normal rats and the mechanism underlying the improvement of its symptoms by LH. LH attenuated liver damage and reduced oxidative stress after chronic ethanol-induced hepatic injury in normal rats. LH treatment reduced hepatic injury biomarkers of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT). LH treatment also decreased levels of 8-hydroxy-deoxyguanosine (8-OHdG) as oxidative stress marker. LH may prove beneficial to prevent the liver damage of chronic ethanol, at least in part, by alleviating oxidative stress.

Effect of repeated oral administration of chondroitin sulfate on neuropathic pain induced by partial sciatic nerve ligation in mice.

We examined whether chondroitin sulfate (CS), a compound used to treat osteoarthritis and joint pain, is effective against partial sciatic nerve ligation (PSNL)-induced neuropathic pain. Repeated oral administration of CS (300 mg/kg, b.i.d. for 20 days) resulted in inhibition of tactile allodynia observed 21 days after PSNL. On day 21, phosphorylation of spinal p38 mitogen-activated protein kinase (MAPK) was attenuated by CS. CS also inhibited c-Fos upregulation in ipsilateral deep dorsal horn (laminae III-IV) neurons, which receive Aß-fiber afferent inputs. These findings suggest that CS attenuates PSNL-induced tactile allodynia by inhibiting spinal p38 MAPK phosphorylation and Aß-fiber activation.

Efficacy of Chondroitin Sulfate for Painful Knee Osteoarthritis: A One-Year, Randomized, Double-Blind, Multicenter Clinical Study in Japan.

We explored the effects of chondroitin sulfate on knee osteoarthritis in a one-year, randomized, double-blind, dose-comparison study. Patients with painful, Kellgren-Lawrence grade 2-3, osteoarthritis of the knee were treated with oral chondroitin sulfate at a dose of either 260 mg/d (low-dose group, control group) or 1560 mg/d (high-dose group). Symptoms were evaluated by the Lequesne's index and visual analog scale for pain. We made subgroup analyses according to background symptom severity (Lequesne's index ≥8 or <8) in 73 patients. Serum level of cartilage oligomeric matrix protein and hyaluronic acid were also determined. In the subgroup with severe symptoms (Lequesne's index ≥8), the chondroitin sulfate dose of 1560 mg/d improved pain faster after 6 and 9 months' therapy. However, no dose-related effects were found on cartilage oligomeric matrix protein or hyaluronic acid levels. Chondroitin sulfate also had good tolerability. We conclude that chondroitin sulfate is useful for pain control in knee osteoarthritis.

Evaluation of the Interaction between Pesticides and a Cell Membrane Model by Surface Plasmon Resonance Spectroscopy Analysis.

A surface plasmon resonance (SPR) spectroscopy analysis was used for the characterization of the interaction between pesticides and a cell membrane model. A liposome was immobilized onto the surface of the SPR sensor chip (L1), and the lipid bilayer membrane formed on the sensor chip was regarded as the cell membrane model. The solution containing a pesticide was flowed onto the sensor chip, and an SPR sensorgram, which reflected the interaction between the pesticide and the lipid bilayer membrane, was obtained. As the results, the pattern and strength of the interaction of the pesticides with the cell membrane model were visualized and quantified. Triflumizole, hexythiazox, and pentachlorophenol showed a strong interaction with the lipid bilayer. It is well-known that triflumizole and pentachlorophenol interact with the membrane and reveal toxicities for cell membranes. In addition, there was a tendency for higher residual ratios to be observed when the no observable adverse effect level (NOAEL) values for chronic toxicity (1 year toxicity study in dogs) were lower. We suggest that a novel parameter for the evaluation or presumption of the behaviors and chronic toxicities of pesticides is obtained by the presented method.

Electrochemical extraction of gold from wastes as nanoparticles stabilized by phospholipids.

A simple one-step method for the extraction of gold from wastes as nanoparticles stabilized by phospholipids is demonstrated. This is achieved by applying an AC voltage for 5s to the gold-containing wastes, which act as the electrodes in a buffer solution containing a dispersed phospholipid (1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC). This is an environmentally friendly and rapid method for recovering gold from wastes. The extracted gold nanoparticles have significant potential as a catalyst or biomedical material.

Chondroitin sulfate attenuates formalin-induced persistent tactile allodynia.

We examined the effect of chondroitin sulfate (CS), a compound used in the treatment of osteoarthritis and joint pain, on the formalin-induced tactile allodynia in mice. A repeated oral administration of CS (300 mg/kg, b.i.d.) significantly ameliorated the formalin-induced tactile allodynia from day 10 after formalin injection. On day 14, the phosphorylation of spinal p38 MAPK and subsequent increase in c-Fos-immunoreactive dorsal lumbar neurons were attenuated by the repeated administration of CS. These findings suggest that CS attenuates formalin-induced tactile allodynia through the inhibition of p38 MAPK phosphorylation and subsequent up-regulation of c-Fos expression in the dorsal lumbar spinal cord.

Liver hydrolysate attenuates the sickness behavior induced by concanavalin A in mice.

Liver hydrolysate (LH) is used as a pharmaceutical agent in Japan, to enhance liver function. However, the effects of LH on sickness behavior are unknown. This study investigated the effect of LH on sickness behaviors, such as concanavalin A (ConA)-induced reduction of locomotor activity. ConA treatment significantly decreased locomotor activity. The striatal tyrosine hydroxylase (TH) levels were also significantly decreased following ConA treatment. The decreased locomotor activity and TH levels were significantly reversed by LH treatment. LH may prove beneficial for preventing sickness behavior following ConA treatment, at least in part, by activating TH in the striatum.

Formation of Tetragonally-Packed Rectangular Cylinders from ABC Block Terpolymer Blends.

Effect of composition distribution of ABC linear terpolymers on the formation of periodic structures was investigated. Five poly(isoprene-b-styrene-b-2-vinylpyridine) (ISP) triblock terpolymers with almost constant molecular weights of ca. 130k and with similar center-block fraction at around 0.55, were blended variously. It has been found that tricontinuous gyroid structures gradually transform into a cylindrical structure whose rectangular cylinders are packed tetragonally if composition distribution increases. Further experiments by 3D-TEM observation on binary equimolar mixtures of two molecules with similar molecular weights of 122k and 124k, giving the average composition of φI/φS/φP = 0.23/0.59/0.18, has verified to show more evident rectangular-shaped cylinders with 4-fold symmetry. This new structure, having periodic surfaces with nonconstant mean-curvature, could be formed due to the systematic localization of component polymer chains along the domain interfaces.

Liver hydrolysate assists in the recovery from physical fatigue in a mouse model.

It is reported that liver hydrolysate (LH) enhances liver function. However, the effects of LH on physical fatigue are unknown. The aim of this study was to investigate the effect of LH on alterations in locomotor activity and energy metabolism such as 5'-AMP-activated protein kinase (AMPK), glycogen content, and blood lactic acid, after forced walking. Adult male ddY mice were used. Locomotor activity, AMPK phosphorylation, and glycogen content in the liver and soleus muscle, as well as blood lactic acid were determined following LH treatment before and/or after forced walking. The locomotor activity significantly decreased after forced walking for 3 h. Two administrations of LH (30 or 100 mg/kg) significantly increased the locomotor activity, while a single administration either before or after forced walking did not show any specific effect. Administering LH twice activated AMPK in the liver and soleus muscle. Glycogen levels significantly decreased in both the liver and soleus muscle after forced walking, whereas the blood lactate level significantly increased. In contrast, administering LH twice increased muscle glycogen and decreased blood lactic acid. These findings indicate that LH produced an anti-fatigue effect and that this effect appears to involve the efficient glycogen utilization through activation of AMPK.

[Effects of liver hydrolysate on the blood glucose in metabolic syndrome model rats (SHR/NDmcr-cp)].

Insulin resistance associated with visceral fat obesity has been suggested to be the pathological basis of metabolic syndrome. Many studies have demonstrated increased oxidant stress in diabetic patients and animal models of diabetes mellitus. In this study, the effect of liver hydrolysate administration on the blood glucose was examined in SHR/NDmcr-cp (SHR-cp) rats that show spontaneously occurring metabolic syndrome-like abnormalities. The SHR-cp rats were fed diets containing 5% liver hydrolysate for 12 weeks, and the fasting blood glucose and HbA1c were determined every 3 weeks. After administration of the liver hydrolysate-containing feed for 12 weeks, an oral glucose tolerance test was conducted and the plasma angiotensin II (AngII) concentrations were determined. The liver hydrolysate administration had no effect on the blood insulin levels in the oral glucose tolerance test, but significantly inhibited the d-glucose-induced increases of the blood glucose levels. Furthermore, the liver hydrolysate had almost no effect on the fasting blood glucose level, but tended to inhibit the increase of HbA1c. The plasma AngII concentration after the 12-week administration of liver hydrolysate remained significantly lower than that in the control group. These results indicate that a component of liver hydrolysate inhibits d-glucose-induced increase of the blood glucose level, and may improve insulin resistance. The angiotensin converting enzyme (ACE)-inhibiting effect and antioxidant effect of liver hydrolysate may be involved in this effect.

Observation of beat oscillation generation by coupled waves associated with parametric decay during radio frequency wave heating of a spherical tokamak plasma.

We present an observation of beat oscillation generation by coupled modes associated with parametric decay instability (PDI) during radio frequency (rf) wave heating experiments on the Tokyo Spherical Tokamak-2. Nearly identical PDI spectra, which are characterized by the coexistence of the rf pump wave, the lower-sideband wave, and the low-frequency oscillation in the ion-cyclotron range of frequency, are observed at various locations in the edge plasma. A bispectral power analysis was used to experimentally discriminate beat oscillation from the resonant mode for the first time. The pump and lower-sideband waves have resonant mode components, while the low-frequency oscillation is exclusively excited by nonlinear coupling of the pump and lower-sideband waves. Newly discovered nonlocal transport channels in spectral space and in real space via PDI are described.