PROX1 is a regulator of neuroendocrine-related gene expression in lung carcinoid.

Lung neuroendocrine neoplasms (NENs) are a diverse group of tumors characterized by neuroendocrine (NE) differentiation. Among lung NENs, lung carcinoid (LC) is a rare tumor with unique characteristics. Recent research has highlighted the importance of transcription factors (TFs) in establishing gene expression programs in lung NENs such as small cell lung carcinoma. However, the TFs that control the gene expression of LC are largely unknown. In this study, we report the expression and potential function of a TF called Prospero homeobox protein1 (PROX1) in LC. Publicly available transcriptome data suggested that PROX1 was highly expressed in LC tissues, which was confirmed by immunohistochemical analysis on a tissue microarray. Knockdown of PROX1 did not impact the cellular viability of an LC-derived cell line, NCI-H727. Meanwhile, transcriptome analysis revealed that PROX1 knockdown altered the expression of genes involved in NE differentiation. ASCL1, CHGA, CALCA, and LINC00261 were suggested as downstream genes of PROX1. These findings indicate that PROX1 may play an important role in the NE identity of LC by regulating the expression of key target genes.

Semi-in vitro detection of Mg2+-dependent DNase that specifically digest mitochondrial nucleoids in the zygote of Physarum polycephalum.

The maternal/uniparental inheritance of mitochondria is controlled by the selective elimination of paternal/uniparental mitochondria and digestion of their mitochondrial DNA (mtDNA). In isogamy, the selective digestion of mtDNA in uniparental mitochondria is initiated after mating and is completed prior to the elimination of mitochondria, but the molecular mechanism of the digestion of uniparental mtDNA remains unknown. In this study, we developed a semi-in vitro assay for DNase, wherein the digestion of mitochondrial nucleoids (mt-nucleoids) was microscopically observed using isolated mitochondria from Physarum polycephalum and the DNase involved in uniparental inheritance was characterized. When myxamoebae of AI35 and DP246 are crossed, mtDNA and mt-nucleoid from only the DP246 parent are digested. The digestion of mt-nucleoids was observed in zygotes 3 h after plating for mating. During the digestion of mt-nucleoids, mitochondrial membrane integrity was maintained. In the semi-in vitro assay, the digestion of mt-nucleoids was only observed in the presence of Mg2+ at pH 7.5-9.0. Moreover, such Mg2+-dependent DNase activity was specifically detected in mitochondria isolated from zygotes 3 h after plating for mating. Therefore, Mg2+-dependent DNase is potentially involved in uniparental inheritance. Our findings provide insights into the DNase involved in uniparental inheritance and its regulatory mechanism.

A modified Terrono classification for Type 1 thumb deformity in rheumatoid arthritis: a cross-sectional analysis.

The most common thumb deformity in rheumatoid arthritis is Nalebuff Type 1 deformity (boutonniere deformity). Type 1 deformity severely impairs hand function, and this impairment is evaluated by the Terrono classification. In some cases, the Terrono classification incorrectly categorizes advanced thumb deformity into earlier stages. We modified the Terrono classification by assessing the active range of motion of the interphalangeal joint prior to assessing the passive range of movement of the metacarpophalangeal joint. An active range of movement of the interphalangeal joint was strongly correlated with hand function. In 55 hands that we treated between 2004 and 2015, we compared the modified classification with the original Terrono classification. Our modified classification could detect advanced deformity earlier, and was more strongly correlated with hand function. Additionally, correlation analysis showed that advanced Type 1 deformity should be treated first, even in cases with severe ulnar drift. Our results suggest that the modified classification may benefit the treatment of Type 1 deformity, including joint-preserving surgery. Level of evidence: III.

A new assessment tool for ulnar drift in patients with rheumatoid arthritis using pathophysiological parameters of the metacarpophalangeal joint.

OBJECTIVES: To establish a new assessment tool for ulnar drift (UD) in rheumatoid arthritis (RA). METHODS: We established an observational cohort of 67 patients (134 rheumatoid hands) beginning in 2004. Fifty-two patients (100 hands) had follow-up in 2009 and 37 patients (63 hands) completed follow-up in 2015. UD was evaluated with the Fearnley classification and our scoring method, which assesses four parameters of the metacarpophalangeal joint. Cluster analysis using UD parameters divided hands into groups. Changes in UD over time, correlation of the Fearnley stage and cluster with a functional assessment, and reliability of the parameters were analyzed. RESULTS: UD increased and worsened over time according to the trend test. A dendrogram indicated five clusters would be appropriate. Both the Fearnley classification and cluster were associated with function; however, our method related to function more linearly (R-squared: 0.42). We found one type of hand in which bone destruction precedes the joint dislocation and one type in which joint dislocation progresses with little deviation during UD progression. CONCLUSION: Our UD evaluation appeared to be simple and related to function. Additionally, it enables dividing UD hands into five stages. Thus, our assessment should be beneficial compared to the Fearnley classification in considering treatments of UD.

How do anti-TNF therapies affect gait function in patients with rheumatoid arthritis?

AIM: The aim of the present study was to investigate the influence of anti-tumor necrosis factor (anti-TNF) agents on gait function in patients with rheumatoid arthritis (RA). METHODS: Nine subjects with RA who were being treated with anti-TNF agents, participated in this study. A motion capture system was utilized, and data from the force plate and captured three dimensional motions were analyzed.Gait evaluation was performed before and 5.8 ± 2.6 months after introducing the anti-TNF agent. Stride, gait velocity and joint moments were calculated. In addition, an index of balancing weight of the lower extremities was determined. RESULTS: Stride length averaged 45.8 cm at baseline and 53.1 cm at the time of follow-up, and gait velocity averaged 0.9 m/s at baseline and 1.1 m/s at the time of follow-up. At heal contact, the joint moment of hip extension increased from 0.37 to 0.49, while ankle joint dorsiflexion moment increased from 0.08 to 0.13. During mid-stance, knee joint extension moment decreased from 0.16 to 0.06. At toe-off, hip joint flexion moment increased from 0.60 to 0.80, and ankle joint dorsiflexion moment increased from 0.80 to 1.05. The index of balancing weight of the lower extremities increased from 19.6 to 20.9 N. CONCLUSION: The induction of anti-TNF therapies improved alterations in shock absorption in the early stance phase, balancing weight of the lower extremities in mid-stance, and increased push-off power in the later stance phase.

Rheumatoid arthritis of the hand: a five-year longitudinal analysis of clinical and radiographic findings.

OBJECTIVES: Treatments for rheumatoid arthritis (RA) have improved since methotrexate and biological agents were approved; however, few longitudinal analyses have tracked joint destruction, deformity progression, or functional impairments that directly affect the activities of daily living. Due to the consequences of functional impairments, we conducted this study to glean more information regarding deformity progression over time. METHODS: This study enrolled 134 hands in 67 RA patients with hand deformities in 2004. After 5 years, 100 hands in 52 patients were eligible for the final assessment. Analyses consisted of morphological and radiographical evaluations of deformities, functional evaluations by questionnaires and the modified Kapandji index, and activity evaluations. RESULTS: In this period, the type I deformity (Nalebuff and Millender, Orthop Clin North Am 6(3):753-63, 1975) was the most common thumb deformity. Swan-neck and boutonnière finger deformities also progressed. At the 5-year follow-up, questionnaire score worsened, when disease activity was high. CONCLUSIONS: Our study showed that there was a marked progression in hand deformities in RA patients over a 5-year period. In order to assist RA patients in performing the activities of daily living, medical and rehabilitative interventions should target the restoration of functional loss through joint destruction as well as the prevention of disease progression.

Measurement of rehabilitation in thumb MP joint subluxation due to rheumatoid arthritis.

As treatment for subluxation due to rheumatoid arthritis (RA), rehabilitation by hand therapy is one option, but the number of therapist is not sufficient. Therefore, a device for rehabilitation of thumb metacarpophalangeal (MP) joint subluxation has been developed. To improve the device, it is necessary to measure in close proximity to the actual rehabilitation. Therefore, the authors tried to measure two kinds of rehabilitation by using motion capture and a contact force sensor. To measure rehabilitation movements, three markers were attached to the metacarpal bone, six markers were attached to each side of the interphalangeal (IP) joint, MP joint and proximal phalanx of the right thumb of the subjects, and a finger model was created by these markers. Further, three markers were placed on the left index of the therapist, and force direction was calculated by these markers. Measurement was conducted on healthy subjects, Rehabilitation was performed by the person who is not a therapist, but received the guidance of the doctor who is coauthor. As a result, the authors could measure rehabilitation by hand therapy, force, point of action and displacement. The results suggest that rehabilitation with traction twice as efficient as that without traction. Furthermore, it was found that rehabilitation is possible with calculated force, and the force is reproducible by the actuator in the device.

Analysis of the mineral composition of taro for determination of geographic origin.

The mineral composition of taro ( Colocasia esculenta (L.) Schott) was analyzed to develop a method to distinguish taro produced in Japan and China. The concentrations of 15 elements (Al, Ca, Cl, Mg, Mn, Br, Co, Cr, Cs, Fe, K, Na, Rb, Sc, Zn) were assayed using instrumental neutron activation analysis. The concentrations of NO(3)(-), SO(4)(2-), H(2)PO(4)(-), Cl(-), malate, and oxalate were measured by ion chromatography. The mean concentrations of H(2)PO(4)(-), Co, Cr, and Na significantly differed (P < 0.01) between taro grown in Japan and that grown in China. Discriminant analysis was performed to identify the most efficient combination of elements and compounds to discriminate the taro geographic origin. The highest percentage of correct classification was achieved with a two-variable model including H(2)PO(4)(-) and Co (100% for Japanese, 93.75% for Chinese). Principal component analysis and cluster analysis using all of the assayed elements and compounds were also conducted to determine which elements significantly accounted for the variation of the taro mineral composition. We report on the potential of H(2)PO(4)(-) and Co concentrations to differentiate taro grown in China and Japan and discuss the sources of variability in the taro mineral composition of our samples.

Relationships among blood leptin and adiponectin levels, fat mass, and bone mineral density in Japanese pre- and postmenopausal women.

We conducted a survey of 111 healthy middle-aged and older women, aged 40 to 80 years, to elucidate the relationships between blood leptin and adiponectin levels and bone mineral density (BMD) in September 2008. We examined the associations between the blood levels of these adipocytokines and the lumbar spine (L2-L4), left femoral, and distal forearm BMD after adjustment for the age and body fat percentage. No correlation was observed between leptin and the BMD. This is presumably due to the fact that the influence of menopause, age, duration of postmenopausal period, and body fat percentage on the BMD is greater than that of leptin levels in healthy women. The adiponectin levels were significantly correlated negatively with the lumbar spine and femoral BMD in premenopausal women, and with forearm BMD in postmenopausal women, regardless of adjustment for age and body fat percentage. It seems likely that adiponectin influences the BMD at different skeletal sites in pre- and postmenopausal women.

A Case of Villoglandular Papillary Adenocarcinoma of the Uterine Cervix Diagnosed during Early Pregnancy Followed by Successful Term Delivery.

Villoglandular papillary adenocarcinoma (VPA) is a very rare subtype of adenocarcinoma of the uterine cervix, but a well-recognized variant of cervical adenocarcinoma with a favorable prognosis and generally occurring in women of child-bearing age. Only five cases of VPA and pregnancy have been reported. Herein, we report a case of VPA diagnosed during early pregnancy and managed successfully with conservative measures; our patient delivered a healthy baby in full term. A successful pregnancy can be completed in patients with VPA without lymph-vascular invasion, when treated conservatively. This management is particularly desirable in young women to preserve reproductive capability.

Lymphoepithelioma-like carcinoma of the uterine cervix.

PURPOSE: To elucidate the clinicopathologic features of lymphoepithelioma-like carcinoma (LELC) of the uterine cervix, we examined three Japanese cases. METHODS: We collected three cases of LELC of the uterine cervix between 2000 and 2007. We examined these patients' clinicopathologic data, Epstein-Barr virus (EBV) and human papilloma virus (HPV) infectious status, and infiltrated lymphocyte population. RESULTS: Our patients had disease Fédération Internatinale de Gynécologie et d'Obstétrique stages I and II. All of them were free of disease at the time of the study. Macroscopically, one of the three tumors was polypoid. All tumor cells were negative for EBV and HPV using in situ hybridization and immunohistochemistry. The inflammatory background contained many CD3(+) and CD8(+) cells, but there were few CD4(+), CD20(+), or CD79a(+) cells. CONCLUSIONS: In our Japanese series, LELC of the uterine cervix showed good prognosis, and there is no relationship between this carcinoma and EBV or HPV infection.

The effects of experimental neurolysis on ectopic firing in a rat chronic constriction nerve injury model.

PURPOSE: We studied the effects of experimental neurolysis on ectopic firing in a rat chronic constriction nerve injury (CCI) model. METHODS: Sixteen Wistar rats were used as CCI models; 8 in a neurolysis group and 8 in a sham operation group. Eight additional Wistar rats were used in a normal control group. The CCI model was created by loosely ligating the sciatic nerve with 4-0 chromic gut sutures. Seven days after surgery the same portion of the sciatic nerve, now embedded in scar tissue, was exposed. For the neurolysis group all sutures and scar tissue around the nerve were removed, and for the sham operation group only exposure of the sciatic nerve embedded in scar tissue was performed. Fourteen days after the first surgery the spinal cords of all animals in the 3 groups were transeated at the most rostral level of the spinal cord and ectopic firing was recorded antidromically from the sural nerve. The spontaneous ectopic firing frequency and the firing pattern at rest and the ectopic firing frequency under a hypoxic condition were analyzed. RESULTS: The ectopic firing frequency in the neurolysis group was significantly lower than that of the sham operation group but higher than that of the normal control group. Also the appearance rate of an on-off pattern was 0% in the neurolysis and normal control groups and 38% in the sham operation group. Finally the accumulated number of ectopic firings under a hypoxic condition was significantly smaller in the neurolysis and normal control groups than that of the sham operation group. CONCLUSIONS: Experimental neurolysis significantly improved the abnormal ectopic firing frequency and on-off firing pattern in the injured nerve of the CCI model. These findings may explain the efficacy of neurolysis on sensory symptoms such as numbness or spontaneous pain in chronic compression neuropathy.

Effect of sodium channel blocker (mexiletine) on pathological ectopic firing pattern in a rat chronic constriction nerve injury model.

We studied the efficacy of mexiletine as a sodium channel blocker for neuropathic pain by investigating the effect of mexiletine on the pathological ectopic firing pattern in a chronic constriction nerve injury (CCI) model. The experiment was conducted with 60 male Wistar rats. The CCI model was created by loosely ligating the sciatic nerve. After breeding 7 days, the frequency and pattern of ectopic firing antidromically recorded from the sural nerve and the amplitude of antidromic sensory nerve-evoked potential were analyzed. The CCI rats were given an intravenous injection of normal saline and mexiletine (5 or 15 mg/kg). Mexiletine significantly suppressed spontaneous firing frequency, an on-off firing pattern that consisted of cyclic bursting spikes and ectopic firing generation under the hypoxic condition. Mexiletine did not influence the amplitude of A-delta component in the antidromic sensory nerve-evoked potential. Mexiletine suppressed ectopic firing by blocking activity of the abnormal sodium channel at the nerve-injured site and dorsal root ganglion without blocking nerve conduction. This study suggests that mexiletine is useful for treating neuropathic pain in peripheral neuropathy.

Recurrent extensor tendon rupture in adult-onset dermatomyositis: a case report.

We report on a case in which recurrent extensor tendon rupture was caused by tenosynovitis without skin ulcer and calcinosis in adult-onset dermatomyositis involving the hand. Proliferative tenosynovitis of the extensor tendons led to recurrent elongation or rupture of the extensor tendons, and tendon graft produced the good postoperative result in this case.

Electrophysiological study on primary afferent properties of a chronic constriction nerve injury model in spinal rats.

A chronic constriction nerve injury (CCI) model of the rat sciatic nerve is known to exhibit neuropathic pain behavior. The authors conducted electrophysiological analysis for the primary afferent properties of this model in a decerebrate spinal preparation. In the CCI model, electrical transcutaneous stimulation for A-delta and C-fibers showed a low current threshold to elicit the flexion withdrawal reflex. The antidromic ectopic firing activity recorded from the sural nerve showed abnormal firing patterns, which were not seen in normal rats, as follows: (1) an increase of spontaneous firing frequency, (2) development of an on-off pattern that consisted of cyclic burst spikes, and (3) increased firing number under the hypoxic condition. The amplitude of the A-delta component in the antidromic sensory nerve-evoked potential was lower than that in normal rats. The current study clarified the electrophysiological parameters reflecting pathological hypersensivity and excitability of primary afferents in the CCI model, which could not found by behavioral analysis. These results may be useful in future studies evaluating possible treatments of neuropathic pain.

[Full-field digital mammography with amorphous silicon-based flat- panel detector: physical imaging characteristics and signal detection].

The physical characteristics of a clinical amorphous silicon-based flat-panel imager for full-field digital mammography were investigated. Pre-sampled modulation transfer functions (MTF) were measured by using a slit method. Noise power spectra were determined for different input exposures by fast Fourier transform. The MTFs of full-field digital mammography systems showed significantly higher values than those of the computed radiography (CR) system. The full-field digital mammography system showed a lower noise level than that of the CR system under the same exposure conditions. Contrast detail analysis has been performed to compare the detectability of the full-field digital mammography system with that of the screen-film (Min-R 2000/Min-R 2000) system. The average contrast-detail curves of digital and film images were obtained from the results of observation. Image quality figures (IQF) were also calculated from the individual observer performance tests. The results indicated that the digital contrast-detail curves and IQF, on average, are superior to those of the screen-film system.

Dehydroepiandrosterone decreases elevated hepatic glucose production in C57BL/KsJ-db/db mice.

Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia in diabetic db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA suppresses the elevated hepatic gluconeogenic glucose-6-phosphatase (G6Pase) activity and gene expression in C57BL/KsJ-db/db mice. In the present study, we evaluated the total amount of gluconeogenesis using NaH[(14)C]CO(3) and hepatic glucose production using fructose as a substrate in primary cultured hepatocytes. Despite hyperinsulinemia, the glucose production of db/db mice in the total body and hepatocytes was elevated as compared to their heterozygote littermate C57BL/KsJ-db/+m mice. Administration of DHEA significantly decreased the blood glucose level and increased the plasma insulin level in db/db mice. Administration of DHEA decreased the elevated total body and hepatic glucose production in db/db mice. In addition, the glucose production in the primary cultured hepatocytes of db/db mice was decreased significantly by the direct addition of DHEA or DHEA-S to the medium. These results suggest that administration of DHEA suppresses the elevated total body and hepatic glucose production in db/db mice, and this effect on the liver is considered to result from increased plasma insulin and DHEA or DHEA-S itself.

Enantioselective aza-Henry reaction catalyzed by a bifunctional organocatalyst.

[reaction: see text] The aza-Henry reaction of imines with nitroalkanes was promoted by chiral thiourea with an N,N-dimethylamino group to give beta-nitroamines with good enantioselectivity. Various N-protected imines were examined as substrates. N-Phosphinoylimine gave the best result in terms of chemical yield and enantioselectivity (up to 91% yield, up to 76% ee).