Clinical benefit of switching from paclitaxel to docetaxel or vice versa in cutaneous angiosarcoma patients resistant to first taxane chemotherapy.

Cutaneous angiosarcoma (CAS) is a rare soft-tissue sarcoma of vascular endothelial origin. Paclitaxel (PTX) and docetaxel (DTX) are used as systemic chemotherapy; however, chemoresistance often occurs in CAS. Switching one taxane to the other (i.e., PTX to DTX, or vice versa) is an option when the first taxane is no longer effective in malignant cancers such as ovarian or breast cancer. However, the efficacy of the same strategy in CAS has not been reported. Herein, we report the clinical response of switching one taxane-based chemotherapy to the other in CAS patients with resistance to the first taxane. Twelve CAS patients were included for analyses. In all patients, the median overall survival from the start of the first taxane treatment was 29.0 months (range, 6.47-58.5). During the first taxane, the median PFS for all patients was 5.96 months (1.81-47.1). Similarly, the median (range) PFS for all patients during the second taxane was 5.87 months (1.60-18.2). Furthermore, the median OS was 22.7 months (PTX to DTX) and 39.5 months (DTX to PTX) (p = 0.307). The median PFS during the first taxane was 5.14 (PTX to DTX) and 12.5 months (DTX to PTX), respectively (p = 0.380). The median PFS during the second taxane was 3.5 (PTX to DTX) and 7.1 months (DTX to PTX), respectively (p = 0.906). The objective response rate, defined as the sum of complete response (CR) and partial response (PR) rates, was 16.7%. The disease control rate, defined as the sum of CR, PR, and stable disease rates, was 50%. The frequency of adverse events during the second taxane was the same between the two groups (p > 0.999). Our report suggests that CAS patients could benefit from the second taxane treatment if the tumor is resistant to the first taxane.

Skull metastases from extramammary Paget's disease emerging 8 years after initial treatment with no local progression: illustrative case.

BACKGROUND: The foci of distant metastasis from extramammary Paget's disease (EMPD) are the lung, liver, truncal bones, vertebrae, and brain. However, skull metastases have not been reported. OBSERVATIONS: The authors treated a patient with calvarial and skull base metastases from EMPD who had undergone wide local resection of EMPD 8 years before, and they report his clinical course. LESSONS: Because EMPD with distant metastasis is fatal, it should be recognized that EMPD can metastasize to the skull even when it seemed to be in remission for several years.

Safety and Efficacy of FIT039 for Verruca Vulgaris: A Placebo-Controlled, Phase I/II Randomized Controlled Trial.

TRIAL DESIGN: Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris. METHODS: Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions. RESULTS: A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups. CONCLUSIONS: No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study.

Hydrophilic Shell Matrix Proteins of Nautilus pompilius and the Identification of a Core Set of Conchiferan Domains.

Despite being a member of the shelled mollusks (Conchiferans), most members of extant cephalopods have lost their external biomineralized shells, except for the basally diverging Nautilids. Here, we report the result of our study to identify major Shell Matrix Proteins and their domains in the Nautilid Nautilus pompilius, in order to gain a general insight into the evolution of Conchiferan Shell Matrix Proteins. In order to do so, we performed a multiomics study on the shell of N. pompilius, by conducting transcriptomics of its mantle tissue and proteomics of its shell matrix. Analyses of obtained data identified 61 distinct shell-specific sequences. Of the successfully annotated 27 sequences, protein domains were predicted in 19. Comparative analysis of Nautilus sequences with four Conchiferans for which Shell Matrix Protein data were available (the pacific oyster, the pearl oyster, the limpet and the Euhadra snail) revealed that three proteins and six protein domains were conserved in all Conchiferans. Interestingly, when the terrestrial Euhadra snail was excluded, another five proteins and six protein domains were found to be shared among the four marine Conchiferans. Phylogenetic analyses indicated that most of these proteins and domains were probably present in the ancestral Conchiferan, but employed in shell formation later and independently in most clades. Even though further studies utilizing deeper sequencing techniques to obtain genome and full-length sequences, and functional analyses, must be carried out in the future, our results here provide important pieces of information for the elucidation of the evolution of Conchiferan shells at the molecular level.

Insights into the Evolution of Shells and Love Darts of Land Snails Revealed from Their Matrix Proteins.

Over the past decade, many skeletal matrix proteins that are possibly related to calcification have been reported in various calcifying animals. Molluscs are among the most diverse calcifying animals and some gastropods have adapted to terrestrial ecological niches. Although many shell matrix proteins (SMPs) have already been reported in molluscs, most reports have focused on marine molluscs, and the SMPs of terrestrial snails remain unclear. In addition, some terrestrial stylommatophoran snails have evolved an additional unique calcified character, called a "love dart," used for mating behavior. We identified 54 SMPs in the terrestrial snail Euhadra quaesita, and found that they contain specific domains that are widely conserved in molluscan SMPs. However, our results also suggest that some of them possibly have evolved independently by domain shuffling, domain recruitment, or gene co-option. We then identified four dart matrix proteins, and found that two of them are the same proteins as those identified as SMPs. Our results suggest that some dart matrix proteins possibly have evolved by independent gene co-option from SMPs during dart evolution events. These results provide a new perspective on the evolution of SMPs and "love darts" in land snails.

Deciphering deterministic factors of predation pressures in deep time.

Predation pressure occurs as a result of predation frequency and prey vulnerability. Although quantifying these factors individually is essential to precisely understand predation effects on evolution, they have been generally less accessible. Here, using a modified form of Poisson function, we quantified the frequencies and vulnerabilities, as well as the resulting predation pressures, concerning the shell drillers versus prey interactions from the Eocene and Miocene periods. Our analysis quantitatively revealed that low-spired shells tend to show increased vulnerability except for two planispiral species that exhibit an unexpectedly low vulnerability. We then identified septal structures within the two species that resemble those in nautiloids and ammonoids but which provided a defensive role against the predators, enhancing the mean lifetime by approximately 20%. The current approach enables us to quantitatively trace how predation frequency and prey vulnerability have interacted, been transformed spatio-temporally, and been a driving force of evolution at geological time scales.

False-positive serology following intravenous immunoglobulin and plasma exchange through transfusion of fresh frozen plasma in a patient with pemphigus vulgaris.

Intravenous immunoglobulin therapy and plasma exchange through transfusion of fresh frozen plasma are therapeutic options for patients with refractory pemphigus vulgaris. Passive acquisition of various clinically important antibodies through these therapies can occur, leading to false serology and negatively affecting patients' clinical care. It is recommended that dermatologists recognize the possibility of these phenomena and interpret them appropriately. Here, we report false-positive serology following intravenous immunoglobulin therapy and plasma exchange through transfusion of fresh frozen plasma in a patient with refractory pemphigus vulgaris. We also discuss the measure for misinterpretation and unnecessary clinical intervention.

An in-silico genomic survey to annotate genes coding for early development-relevant signaling molecules in the pearl oyster, Pinctada fucata.

The pearl oyster Pinctada fucata has great potential as a model system for lophotrochozoan developmental biology research. Pinctada fucata is an important commercial resource, and a significant body of primary research on this species has emphasized its basic aquaculture biology such as larval biology and growth, aquaculture, pearl formation and quality improvement, shell formation, and biomineralization. Recently, a draft genome sequence of this species was published, and many experimental resources are currently being developed, such as bioinformatics tools, embryo and larva manipulation methods, gene knockdown technique, etc. In this paper, we report the results from our genomic survey pertaining to gene families that encode developmental signaling ligands (Fgf, Hedgehog, PDGF/VEGF, TGFß, and Wnt families). We found most of the representative genes of major signaling pathways involved in axial patterning, as well as copies of the signaling molecule paralogs. Phylogenetic character mapping was used to infer a possible evolutionary scenario of the signaling molecules in the protostomes, and to reconstruct possible copy numbers of signaling molecule-coding genes for the ancestral protostome. Our reconstruction suggests that P. fucata retains the ancestral protostome gene complement, providing further justifications for the use of this taxon as a model organism for developmental genomics research.

[Long-term follow-up of ofloxacin-combined therapy for leprosy patients].

This reports a long-term follow-up study on clinical effects of ofloxacin (OFLX)-combined therapy to 14 leprosy patients with various types and stages. Combined drugs were diaminodiphenyl sulfone (DDS), rifampicin (RFP) and clofazimine. Clinical evaluation of the treatment after OFLX-combined therapy was remarkable improvement 10 cases, improvement 3 and re-exacerbated after improvement 1 to whom clofazimine and minocycline were prescribed. The evaluation during the follow-up was remarkable improvement 10, improvement 1; three cases died of traffic accident or complications not related to chemotherapy and none of them showed relapse of leprosy. Bacterial negativity after onset of OFLX-combined therapy was achieved in about the same periods as RFP-combined therapy. OFLX-combined therapy was effective and safe. This follow-up study supports the efficacy of clinical guideline for the use of new quinolones published by Japanese leprosy Association.

Isolation, cloning, and characterization of a novel phosphomannan-binding lectin from porcine serum.

Mannan-binding protein (MBP) is a C-type serum lectin that is an important constituent of the innate immune defense because it activates the complement system via the lectin pathway. While the pig has been proposed to be an attractive source of xenotransplantable tissues and organs, little is known about porcine MBP. In our previous studies, phosphomannan, but not mannan, was found to be an effective inhibitor of the C1q-independent bactericidal activity of newborn piglet serum against some rough strains of Gram-negative bacteria. In contrast, the inhibitory activities of phosphomannan and mannan were very similar in the case of MBP-dependent bactericidal activity against rough strains of Escherichia coli K-12 and S-16. Based on these findings, we inferred that an MBP-like lectin with slightly or completely different carbohydrate binding specificity might exist in newborn piglet serum and be responsible for the C1q-independent bactericidal activity. Herein we report that a novel phosphomannan-binding lectin (PMBL) of 33 kDa under reducing conditions was isolated from both newborn and adult porcine serum and characterized. Porcine PMBL functionally activated the complement system via the lectin pathway triggered by binding with both phosphomannan (P-mannan) and mannan, which, unlike MBP, was effectively inhibited by mannose 6-phosphate- or galatose-containing oligosaccharides. Our observations suggest that porcine PMBL plays a critical role in the innate immune defense from the newborn stage to adult-hood, and the establishment of a newborn piglet experimental model for the innate immune system studies is a valuable step toward elucidation of the physiological function and molecular mechanism of lectin pathway.

MR imaging of lymph nodes in the head and neck.

This article reviews imaging-based nodal classification, recent advancements in MR imaging techniques for lymph node imaging, and characteristics of MR imaging for necklymphadenopathy. Further technical development of MR imaging is necessary to improve accuracy of diagnosis of lymph node metastases in patients with no head and neck cancer. Development of new tissue-specific MR contrast agents and functional imaging studies to address biologic activity of lymph nodes is essential in the future.

Strategies for sperm chemotaxis in the siphonophores and ascidians: a numerical simulation study.

Chemotactic swimming behaviors of spermatozoa toward an egg have been reported in various species. The strategies underlying these behaviors, however, are poorly understood. We focused on two types of chemotaxis, one in the siphonophores and the second in the ascidians, and then proposed two models based on experimental data. Both models assumed that the radius of the path curvature of a swimming spermatozoon depends on [Ca(2+)](i), the intracellular calcium concentration. The chemotaxis in the siphonophores could be simulated in a model that assumes that [Ca(2+)](i) depends on the local concentration of the attractant in the vicinity of the spermatozoon and that a substantial time period is required for the clearance of transient high [Ca(2+)](i). In the case of ascidians, trajectories similar to those in experiments could be adequately simulated by a variant of this model that assumes that [Ca(2+)](i) depends on the time derivative of the attractant concentration. The properties of these strategies and future problems are discussed in relation to these models.

Paramagnetic effect of supplemental oxygen on CSF hyperintensity on fluid-attenuated inversion recovery MR images.

BACKGROUND AND PURPOSE: Oxygen has a known paramagnetic effect and increases CSF signal intensity on fluid-attenuated inversion recovery (FLAIR) MR images. The purposes of this study were to investigate the effect of supplemental oxygen on CSF signal intensity and the arterial partial pressure of oxygen and to determine the possible synergistic effect of oxygen and albumin on T1 shortening effect in vitro. METHODS: Six healthy volunteers underwent FLAIR MR imaging of the brain before and during inhalation of 10 to 15 L/min of 100% oxygen for < or = 30 min. The signal intensity was measured in the subarachnoid spaces and various tissues and correlated with estimated arterial partial pressure of oxygen and arterial carbon dioxide pressure. In vitro measurements were also obtained by using two sets of saline-filled tubes with various concentrations of albumin, one of which was exposed to increased oxygen levels. In vitro T1 relaxation times were calculated to assess the possible synergistic effect of oxygen and albumin. RESULTS: FLAIR images of healthy volunteers showed increased CSF signal intensity within the basal cisterns and sulci along the cerebral convexities. The CSF hyperintensity was observed immediately after the initiation of supplemental oxygen and remained stable during the oxygen administration. There was approximately a 4- to 5.3-fold increase in signal intensity with supplemental oxygen. The phantom experiments showed a T1 shortening effect of oxygen. Albumin significantly altered T1 relaxation time only at high concentrations of albumin. CONCLUSION: Inhalation of increased levels of oxygen led to readily detectable CSF hyperintensity on FLAIR images of healthy volunteers. No significant synergetic effect of albumin and oxygen was noted.

Store-operated calcium channel regulates the chemotactic behavior of ascidian sperm.

The sperm-activating and -attracting factor released from the eggs of the ascidians Ciona intestinalis and Ciona savignyi requires extracellular Ca(2+) for activating sperm motility and eliciting chemotactic behavior of the activated sperm toward the egg. Here, we show that modulators of the store-operated Ca(2+) channel, SK&F96365, Ni(2+), 2-aminoethoxydiphenylborane, and thapsigargin inhibit the chemotactic behavior of the ascidian sperm; on the other hand, blockers of voltage-dependent Ca(2+) channels did not inhibit the chemotaxis, even though they inhibited the sperm activation operated by voltage-dependent Ca(2+) channels. The blockers of store-operated Ca(2+) channels also inhibited the asymmetrical flagellar beating and turning movements of the ascidian sperm, which are typical signs of sperm chemotaxis. Depletion of internal Ca(2+) stores by thapsigargin induced capacitative Ca(2+) entry into the sperm, which was blocked by SK&F96365. These results suggest that the intracellular Ca(2+) concentration increase through the store-operated Ca(2+) channels induces asymmetrical flagellar movements to establish the chemotactic behavior of the sperm.

MR imaging of lymph nodes in the head and neck.

This article reviews imaging-based nodal classification, recent advancements in MR techniques for lymph node imaging, and characteristics of MR imaging for neck lymphadenopathy. Further technical development of MR imaging is necessary to improve accuracy of lymph node metastases in patients with N0 neck. Development of new tissue-specific MR contrast agents and functional imaging studies to address biologic activity of lymph nodes are essential in the future.