Geological-Geophysical and Oceanographic Research in the Sea of Japan, Tatar Strait, on Cruise 61 of the R/V Akademik Oparin.

The paper presents brief results of comprehensive studies of the water area of the Tatar Strait and Sea of Japan obtained on cruise 61 of the R/V "Akademik Oparin" in November-December 2020. The bottom relief and geophysical and gas-geochemical fields were refined, and new features of the geochemistry and mineralogy of bottom sediments were revealed.

Sex determination from partial segments and maximum femur lengths in Koreans using computed tomography.

BACKGROUND: The aim of this study was to establish standards for determining sex from fragmentary and complete femurs in a Korean population. MATERIALS AND METHODS: The statistical analysis of 12 variables (6 about breadth and 6 about length) based on 100 Korean femurs (from 50 males and 50 females) showed that all variables have significant sex differences. RESULTS: The most accurate discriminant variable was the condylar breadth parallel with epicondylar breadth (87.6% accuracy). In contrast, the transverse shaft diameter was not a discriminant variable for sex determination (67.0% accuracy). Breadth-related variables were generally more accurate than length-related variables. Three variables (vertical diameter of the neck [VDN], medial epicondylarlength [MCL], and condylar breadth [CB]) were selected from stepwise analysis fordiscriminating sex (93.5% accuracy). The discriminating equation was as follows: 0.171 × VDN + 0.172 × MCL + 0.128 × CB2 - 21.471. CONCLUSIONS: The results of this study are helpful for determining sex, even if a femur is found in a fragmented condition in the field.

Interventional stroke therapies in the elderly: are we helping?

BACKGROUND AND PURPOSE: It is unclear whether endovascular therapies for the treatment of AIS are being offered or are safe in older adults. The use and safety of endovascular interventions in patients older than 75 years of age were assessed. MATERIALS AND METHODS: A retrospective review of patients with AIS 75 years or older (n = 37/1064) was compared with a younger cohort (n = 70/1190) by using an established data base. Admission and discharge NIHSS scores, rates of endovascular treatment, SICH, in-hospital mortality, and the mBI were assessed. RESULTS: Rates of endovascular treatments were significantly lower in older patients (5.9% in the younger-than-75-year versus 3.5% in the older-than-75-year cohort, P = .007). Stroke severity as measured by the NIHSS score was equivalent in the 2 age groups. The mBI at 12 months was worse in the older patients (mild or no disability in 52% of the younger-than-75-year and 22% in the 75-year-or-older cohort, P = .006). Older patients had higher rates of SICH (9% in younger-than-75-year versus 24% in the 75-year-or-older group, P = .04) and in-hospital mortality (26% in younger-than-75-year versus 46% in the 75-year-or-older group, P = .05). CONCLUSIONS: Patients older than 75 years of age were less likely to receive endovascular treatments. Older patients had higher rates of SICH, disability, and mortality. Prospective randomized trials are needed to determine the criteria for selecting patients most likely to benefit from acute endovascular therapies.

Application of scanning probe lithography to graphite patterning.

We applied the scanning probe lithographic technique to a graphite patterning in air and analyzed the patterned sample with the lateral force microscopy and Raman spectroscopy. The local electric field generated from a tip caused either etching or oxidization depending on the electric field intensity in air. We have found that the frictional force between the tip and local oxidized graphite surface was increased remarkably from lateral force analysis. Also, it was found that the graphene layer was peeled from the graphite surface in the etching process, which could be a potential tool as a top-down nano-fabrication process for the graphene nano device without contamination.

Characterization of virus distribution in Rock Bream (Oplegnathus fasciatus; Temminck and Schlegel) infected with megalocytivirus.

The distribution of virus-infected cells in the organs of Rock Bream naturally infected with megalocytivirus is reported. Examination of sections of liver, spleen and kidney stained by haematoxylin and eosin (HE) and periodic acid Schiff (PAS) revealed the presence of swollen and degenerate cells having morphology consistent with leucocytes. Many of these cells were shown to contain viral DNA by in-situ hybridization (ISH). Cells containing viral DNA were also found in the connective tissue of other organs in which there was no prominent infiltrate of degenerate leucocytes. Viral DNA was also found in the cytoplasm of leucocytes in blood smears. Transmission electron microscopy (TEM) confirmed the presence of viral particles in the cells within tissue and free within blood. The tissue distribution of virus in this infection is suggested to reflect the infiltration of virus-infected leucocytes.

Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer.

This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m(-2) at week 1 and 250 mg m(-2) weekly thereafter until disease progression. Oxaliplatin (100 mg m(-2)) and leucovorin (100 mg m(-2)) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m(-2)) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1-65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5-6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-alpha levels showed a 100% RR compared to 37.0% in the remaining 27 patients (P<0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment.

Differential alterations in expressions of ryanodine receptor subtypes in cerebellar cortical neurons of an ataxic mutant, rolling mouse Nagoya.

This study aimed to clarify changes in the spatial expressions of types 1, 2 and 3 ryanodine receptors (RyR1, RyR2 and RyR3) in the cerebellum of a Ca(2+) channel alpha(1A) subunit mutant, rolling mouse Nagoya. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed that the mRNA signal levels of RyR1 and RyR3 were altered in the rolling cerebellum, which exhibited lower densities of RyR1 bands and higher densities of RyR3 bands than in the control cerebellum. Quite consistent with the RT-PCR results, the staining intensity of RyR1 and RyR3 was altered in the rolling cerebellum. RyR1 immunostaining appeared in somata and the proximal dendrites of Purkinje cells, and the staining intensity of both subcellular regions was equally lower in all cerebellar lobules of rolling mice than in those of controls. Although RyR3 immunostaining appeared in the dendrites of granule cells, more intense RyR3 staining in rolling mice than in controls was uniformly observed throughout all cerebellar lobules. The present study further examined co-localizations of ryanodine receptor subtypes and voltage-gated Ca(2+) channel alpha(1) subunits in the rolling cerebellum. Somatodendritic RyR1 immunostaining in Purkinje cells overlapped with either a mutated Ca(2+) channel alpha(1A) subunit (P/Q-type), or a Ca(2+) channel alpha(1C) subunit (L-type; dihydropyridine receptor) immunostaining. Immunostaining of these alpha(1) subunits also emerged in granule cells. Those results suggest non-region-related alterations in RyR1 and RyR3 expressions in the rolling mouse cerebellum. Such expressional changes in ryanodine receptor subtypes may be involved in Ca(2+) channel alpha(1A) subunit gene mutation, and may alter regulation of intracellular Ca(2+) concentrations in cerebellar cortical neurons.

The absence of phosphorylated tyrosine hydroxylase expression in the purkinje cells of the ataxic mutant pogo mouse.

The pogo mouse is a new ataxic autosomal recessive mutant that arose in Korean wild mice (KJR/Mskist). Its ataxic phenotype includes difficulty in maintaining a normal posture and the inability to walk in a straight line. Several studies have reported that tyrosine hydroxylase (TH) is persistently ectopically expressed in particular subsets of Purkinje cells in a parasagittal banding pattern in several ataxic mutant mice, e.g. tottering alleles and pogo mice. In this present study, we examined the expression of an enzymatically active form of TH and phosphorylated TH at Ser(40) (phospho-TH) by using immunohistochemistry and double immunofluorescence in the cerebellum of pogo mice. TH immunostaining appeared in some Purkinje cells in pogo, but in only a few of Purkinje cells of their heterozygous littermate controls. In all groups of mice, no phospho-TH immunoreactive Purkinje cells were observed in the cerebellum, although subsets of TH immunoreactive Purkinje cells were found in adjacent sections. This study suggests that TH expression in the Purkinje cells of pogo abnormally increases without activation of this enzyme by phosphorylation. This may mean that TH in the Purkinje cells of these mutants does not catalyse the conversion of tyrosine to l-DOPA, and is not related to catecholamine synthesis.

Corticotropin-releasing factor immunoreactivity increases in the cerebellar climbing fibers in the novel ataxic mutant mouse, pogo.

The ataxic pogo mouse (pogo/pogo) is a novel neurological mutant, which was derived as an inbred strain (KJR/MsKist) from a Korean wild mouse. The pathological manifestations include a difficulty in maintaining a normal posture, the failure of inter-limb coordination and an inability to walk straight. In this study, we examined the distribution of corticotropin-releasing factor (CRF) immunoreactive cerebellar climbing fibres and their projections to tyrosine hydroxylase (TH) immunoreactive Purkinje cells in the cerebellum of the pogo mutant mouse using immunohistochemistry. In the pogo/pogo mouse, a subset of climbing fibres was stained more intensely for CRF than in the control. Moreover, ataxic pogo mouse, neurons of the inferior olivary nucleus projecting climbing fibres were also more intensely stained for CRF than in the control. In the pogo/pogo mouse, TH immunoreactivity was located in the Purkinje cells, whereas no TH expression was found in the control. Double immunostaining for CRF and TH in the pogo/pogo cerebellum revealed that the distribution of TH-immunoreactive Purkinje cells corresponded to terminal fields of CRF-immunoreactive climbing fibres but not to the CRF-immunoreactive mossy fibres. Therefore, we suggest that an increase of CRF level may alter the function of targeted Purkinje cells and that it is related to the ataxic phenotype in the pogo mutant mouse.

Genetic association study of adiponectin polymorphisms with risk of Type 2 diabetes mellitus in Korean population.

AIMS: To investigate any association between Type 2 diabetes mellitus and two single nucleotide polymorphisms (SNPs) in the adiponectin gene, T45G and G276T, in the Korean population. METHODS: We genotyped 427 non-diabetic controls and 493 Type 2 diabetic patients for SNPs T45G and G276T of adiponectin gene, measured plasma adiponectin concentrations, and examined clinical parameters in Koreans. RESULTS: There were no statistically significant differences in allele frequencies of SNPs 45 and 276 comparing control with Type 2 diabetic subjects (T frequency 68.3% vs. 71.6%, P=0.13 for SNP45, G frequency 72.2% vs. 68.9%, P=0.12 for SNP276). The genotype distributions of these SNPs had no association with the risk of Type 2 diabetes and metabolic parameters of insulin resistance. Plasma levels of adiponectin were not statistically different according to T45G and G276T either, in both control and Type 2 diabetic subjects. CONCLUSION: The T45G and G276T of the adiponectin gene may not be an important determinant of Type 2 diabetes or insulin resistance in Korean subjects.

Post-natal changes of cyclin-dependent kinase 5 activator expression in the developing rat cerebellum.

cDNA of cyclin-dependent kinase 5 (Cdk5) was cloned based on its primary sequence homology to Cdc2 and Cdk2. Cdk5 requires the neuronal Cdk5 activators such as p35 or p39(nck5ai) (p39) for its activity. In this study, we examined post-natal changes in the p39 expression pattern during the development of the rat cerebellum. p39 began to express in somata and dendrites of Purkinje cells at post-natal day 3 (PD3). In particular, at PD12, parasagittal bands (stripes) with p39 immunoreactivity were weakly observed. At PD21, p39-immunoreactive stripes were developed when compared with the PD12 group. At this age stage, p39 immunoreactivity became weak in somata of Purkinje cells, not forming stripes. At PD28, a series of parasagittal bands were more distinct than those of the PD21 group, and p39 immunoreactivity disappeared in Purkinje cells, not forming p39 immunoreactive stripes. In the adults, p39 immunoreactivity in Purkinje cells was similar to that found in the PD28 group which showed that parasagittal bands were very narrow, and became progressively more slender. Therefore, we suggest that the post-natal changes of p39 expression in Purkinje cells in the cerebellum is an autonomous characteristic of Purkinje cells with a role of Cdk5 activators.

Ex vivo purging of leukemia cells using tumor-necrosis-factor-related apoptosis-inducing ligand in hematopoietic stem cell transplantation.

The aim of this study was to evaluate the potential of tumor-necrosis-factor-related apoptosis-inducing ligand TRAIL to eradicate leukemia cell lines, while sparing normal hematopoietic stem cells. Human Jurkat and Molt-4 cell lines were used to optimize the purging process in umbilical cord blood (UCB) mononuclear cells. The Jurkat cell line was TRAIL sensitive and TRAIL-resistant Molt-4 cell line became sensitive after being treated with TRAIL and a low dose of doxorubicin (0.1 micro M), but UCB mononuclear cells remained resistant. DR4 expression was increased when Jurkat cells were treated with TRAIL, and DR5 expression increased after exposing Molt-4 cells to TRAIL plus a low dose of doxorubicin for 24 h. The expression of DR4 and DR5 in UCB mononuclear cells was unchanged after treatment with TRAIL, a low-dose doxorubicin, or TRAIL plus a low dose of doxorubicin. In TRAIL-sensitive Jurkat cells, caspases 8, 9, 3, and 7 were activated by TRAIL treatment and activation of caspases was augmented by TRAIL plus a low dose of doxorubicin than TRAIL or a low dose of doxorubicin alone in Molt-4 cells. Experiments involving mixture of UCB mononuclear cells and Jurkat or Molt-4 cells showed a marked eradication of leukemia cells and the limiting dilution assay demonstrated an eradication rate of more than 4 logs after 24 h incubation with 100 ng/ml of TRAIL in Jurkat cells. In the case of Molt-4 cells, the eradication rate was about 3 logs when TRAIL was used in combination with a low dose of doxorubicin. No significant decrease in the number of granulocyte-macrophage colony-forming unit) (CFU-GM) colonies was detected when UCB mononuclear cells were treated with TRAIL in combination with a low dose of doxorubicin. These results suggest that TRAIL offers the possibility of being used as an ex vivo purging agent for autologous transplantation in hematologic malignancies.

Systemic availability of arsenic from oral arsenic-trioxide used to treat patients with hematological malignancies.

AIMS: Arsenic trioxide (As2O3) is increasingly used to treat hematological malignancies. This involves daily intravenous (i.v.) administration for 4-8 weeks, with its attendant drawbacks: inconvenience, risks and expense of maintaining suitable vascular access and hospitalization. We therefore developed an oral formulation, administered it to patients and set out to assess the resulting systemic bioavailability of arsenic. METHODS: With ethics committee approval, nine patients with refractory/relapsed acute myeloid leukemia were recruited after giving informed consent. On day 1, each received 10 mg As2O3 by i.v. infusion over 1 h. Each patient swallowed 10 mg As2O3 in 10 ml oral solution 24 h later (day 2) and on subsequent days thereafter. Prior to and until 48 h post-i.v. dosing, timed venous blood samples were drawn and corresponding plasma and whole blood arsenic concentrations were determined by atomic absorption spectroscopy. Systemic bioavailability was inferred from the area under the arsenic level versus time curve (AUC) using the trapezoidal rule. Day-1 AUC after i.v. dosing was taken to be 100% and that attributed to oral dosing (day 2) was then calculated. The 48-h arsenic levels in blood cells were calculated using hematocrit values and corresponding plasma and whole blood arsenic concentrations. RESULTS: Respective day-2 mean plasma and blood AUCs attributed to oral dosing were 99% and 87% of corresponding day-1 values. On average, 48-h blood cell arsenic levels were 270% greater than in plasma ( P=0.013). No patient suffered unexpected complications, and five went into remission. CONCLUSIONS: Compared with i.v. dosing, our oral As2O3 formulation was more convenient and cost effective, and the ensuing systemic bioavailability of arsenic appeared similar. Arsenic seemed to be concentrated in the cellular fraction of blood 48 h after starting As2O3 treatment.

Intracellular ribozyme applications.

The exquisite target selectivity of trans -acting ribozymes has fostered their use as potential therapeutic agents and tools for down-regulating cellular transcripts. In living cells, free diffusion of RNAs is extremely limited, if it exists at all. Thus, getting ribozymes to base-pair with their cognate targets requires co-localizing the ribozyme transcript with the target RNA. In addition, not all sites along a given target RNA are equally accessible to ribozyme base pairing. Cellular proteins greatly influence the trafficking and structure of RNA, and therefore making ribozymes work effectively in cells a significant challenge. This article addresses the problems of getting engineered ribozymes to effectively pair with and cleave targets in cells. The work described here illuminates methods for target-site selection on native mRNAs, methods for ribozyme expression, and strategies for obtaining a discrete intracellular localization of ribozymes.

Characteristics of community-acquired methicillin-resistant Staphylococcus aureus in infants and children without known risk factors.

This retrospective study sought to determine the characteristics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in patients younger than 18 years without known risk factors who were treated at a teaching hospital in central Taiwan. Epidemiological and clinical data were collected from medical charts. Possible risk factors included hospitalization within the past 6 months, transfer from other hospitals or nursing homes, and having underlying illness. A total of 173 isolates of community-acquired S. aureus were analyzed. Seventeen (9.8%) of these 173 isolates were methicillin-resistant S. aureus collected from patients without risk factors, 31 (17.9%) were methicillin-resistant S. aureus from patients with risk factors, and the other 125 (72.3%) were methicillin-susceptible S. aureus. Most isolates of community-acquired methicillin-resistant S. aureus collected from patients without risk factors (14/17, 82.4%) were obtained from the infected wounds of skin or soft tissues. Only 4 (23.5%) in 17 patients with isolates resistant to methicillin were prescribed antimicrobial therapy with glycopeptides. Nevertheless, all patients recovered without any long-term sequelae. These results highlight the fact that community-acquired methicillin-resistant S. aureus infections occur frequently in Taiwan among patients who have no established risk factors for this infection.

Magnesium isotope separation by ion exchange using hydrous manganese(IV) oxide.

The magnesium isotope effects were investigated by chemical ion exchange with a hydrous manganese(IV) oxide. The capacity of manganese(IV) oxide was 0.5 meq g(-1). The distribution coefficient of magnesium ions on the MnO(2) was determined by a batch method. The heavier isotopes of magnesium were enriched in the solution phase, while the lighter isotopes were enriched in the hydrous MnO(2) phase. The separation factor was determined according to the method of Glueckauf from the elution curve and isotopic assays. The separation factors of (24)Mg(2+)-(25)Mg(2+), (24)Mg(2+)-(26)Mg(2+), and (25)Mg(2+)-(26)Mg(2+) isotope pair fractionations were 1.011, 1.021, and 1.011, respectively.

Morphological characteristics of C1 and C2 adrenergic neurone groups in marmoset monkey brainstem by using antibody against phenylethanolamine-N-methyltransferase.

This work describes a mapping study of phenylethanolamine-N-methyltransferase (PNMT) immunoreactive neurones and fibres in the medulla oblongata of the marmoset monkey, Callithrix jacchus. Two groups of PNMT-immunoreactive neurones were found in the marmoset monkey medulla oblongata: a ventrolateral (C1 group) and a dorsomedial PNMT-immunoreactive cells group (C2 group). The PNMT-immunoreactive cells in the ventrolateral group C1 were found to be located around the lateral reticular nucleus. The PNMT-immunoreactive somata within the ventrolateral medulla are round to oval, and mostly multipolar with branched processes. In the dorsomedial group C2, PNMT-immunoreactive cell bodies appeared near the obex. The majority of the dorsomedial PNMT-immunoreactive neurones were observed in the nucleus tractus solitarius; although some were present in the dorsal motor nucleus of the vagus. The PNMT-immunoreactive somata in the dorsomedial medulla were small and round or ovoid. These results provide information upon the adrenergic system in the medulla oblongata of a species that presents a useful model of a small primate brain, the marmoset monkey.

Identification of structural domains affecting transactivation potential of Nm23.

The strong transactivation activity of the C-terminal half (amino acids 76-152) of Nm23 was reported previously. Here we examined a structural domain preventing or necessary to its transactivation activity. The C-terminal 1/4 (amino acids 109-152) was sufficient for transactivation, but the C-terminal half with a longer N-terminal extension (amino acids 58-152) caused the loss of the transactivation ability. Furthermore, coexpression of the N-terminal half with the C-terminus of Nm23-H1 blocked the transactivation activity of the C-terminal half, where direct interaction of both truncated proteins was demonstrated in vitro. Transactivation activities in the C-terminal halves of the known mutants (P96S, H118F, S120G, and S120A) exhibiting differential antimetastasis effects were also tested. Significant reduction of transactivation activity was observed only in H118F, indicating that NPD kinase active-site histidine is required. This suggests that transactivation potential of Nm23 is related to NDP kinase activity but not to metastasis suppressor activity.

Functional colocalization of ribozymes and target mRNAs in Drosophila oocytes.

The effectiveness of catalytic RNAs (ribozymes) should be increased when they are colocalized to the same intracellular compartment as their RNA targets. We colocalized ribozymes with their mRNA targets in an animal model by using the discrete RNA localization signals present in the 3' untranslated regions (UTRs) of Drosophila bicoid and oskar mRNAs. These signals have been fused to a lacZ mRNA target and hammerhead ribozymes targeted against lacZ. Ribozyme efficacy was first assessed by an oligodeoxyribonucleotide-based assay to identify the most accessible sites for ribozyme interaction on native lacZ transcripts in ovary extracts. The most accessible sequence was used for the design and in vivo testing of a hammerhead ribozyme. When the ribozyme and target with synonymous 3' UTRs were expressed in the same ovaries, colocalization could be indirectly demonstrated by in situ hybridization. Colocalized ribozyme and target mRNAs resulted in a two- to threefold enhancement of ribozyme function compared with noncolocalized transcripts. This study provides the first demonstration of functional ribozyme target colocalization in an animal model.

A case of jellyfish sting.

Jellyfish sting may result in a wide range of symptoms from common erythematous urticarial eruptions to the rare box-jelly induced acute respiratory failure. In Taiwan, with the increasing frequency of international travel, cases of jellyfish sting to foreigners are on the rise. We report a case of jellyfish sting with the rare presentation of painless contact dermatitis. A 38-y-o man accidentally stepped on a sea urchin with his right foot during scuba diving in a beach in Thailand. Traditional therapy with vinegar was applied on the lesion. However, when he returned to Taiwan, erythematous patches on the left thigh with linear radiations to the leg were discovered. The skin lesions had bizzare shapes and showed progressive change. No pain or numbness was noticed. Jellyfish stingwas suspected, topical medications were applied, and the patient recovered without complication. Jellyfish stings usually result in a painful erythematous eruption. In this case, though the lesion involved a large surface, there was no pain. Delayed diagnosis of jellyfish sting was due to the atypical presentation and the physician's unfamiliarity to the Thai jellyfish sting. Awareness to the wide spectrum of jellyfish sting symptoms should be promoted.