The adaptational strategies of the hindlimb muscles in the Tenrecidae species including the aquatic web-footed tenrec (Limnogale mergulus).

The hindlimb muscles in four species of Tenrecidae (Oryzoryctinae: Talazac long-tailed tenrec and web-footed tenrec, Tenrecinae: lesser hedgehog tenrec, and streaked tenrec), were examined macroscopically. The weight ratios of the muscles to the body in the oryzoryctinid species are larger than those in Tenrecinae, since the Oryzoryctinae species have an obviously smaller body from the evolutionary point of view. It can be primarily pointed out that the adaptation of the body size is different between the two subfamilies, and secondarily, that functional adaptation to locomotion is complete within each subfamily. The weight data and the morphological findings demonstrate that the web-footed tenrec possesses an extraordinary large M. semimembranosus in comparison to the Talazac long-tailed tenrec in their weight ratios. This muscle may act as a strong flexor motor in the knee joint during the aquatic locomotion of the web-footed tenrec. Since the other muscles of the web-footed tenrec are similar to those of the Talazac long-tailed tenrec regards weight ratio data, we think that the web-footed tenrec may have derived from a terrestrial ancestor such as the long-tailed tenrecs. In Tenrecinae the streaked tenrec is equipped with larger Mm. adductores, M. semimembranosus and M. triceps surae than the lesser hedgehog tenrec. This species is adapted to fossorial life derived from non-specialized ancestors within the evolutionary lines of the spiny tenrecs.     

Pulmonary synovial sarcoma with polypoid endobronchial growth: a case report, immunohistochemical and cytogenetic study

A rare case of primary pulmonary synovial sarcoma with polypoid endobronchial growth in a 42-year-old Japanese woman is described. Left upper sleeve lobectomy was performed for the polypoid tumor measuring 2.5 cm in the left major bronchus and the patient was treated with adjuvant chemotherapy. Three years later, a recurrent tumor was discovered. Microscopically, this tumor was characterized by a proliferation of oval to spindle-shaped cells arranged in sheets and fascicles and covered by the thin normal bronchial epithelium. Immunohistochemically, tumor cells were positive for vimentin, and focally positive for pancytokeratin recognized by AE1/AE3, cytokeratin 7 and epithelial membrane antigen. A chimera gene, SYT-SSX1, was detected. Recently, primary pulmonary synovial sarcoma is an increasingly recognized clinical entity; however, most of these tumors present as a parenchymal mass. The present case is a unique example of primary synovial sarcoma of endobronchial polypoid type. This case suggests that pulmonary synovial sarcoma might originate from bronchial submucosal stromal tissue.     

Crystal Growth in Poly(L‐lactide) Thin Film Revealed by in situ Atomic Force Microscopy

Direct visualization of crystal growth in poly(L ‐lactide) thin films was carried out by using a temperature‐controlled atomic force microscopy (AFM). At the initial stage of crystallization, edge‐on lamellar crystals have nucleated and elongated. Subsequently, the edge‐on lamellar crystals showed S‐shaped morphology and changed their orientation from edge‐on manner to flat‐on one. The curvature of edge‐on lamellar crystal has been discussed in terms of inclination and distortion of polymer chains in the crystal. In addition, mechanism on the formation of flat‐on crystal from edge‐on lamellae was proposed as derivative growth on the basis of in situ AFM observation of crystal growth and enzymatic degradation.

     

Diversity of Hepatitis G Virus within a Single Infected Individual

The extent of population diversity among GB virus C (GBV-C)/hepatitis G virus (HGV) within a persistently infected individual (Iw) was investigated by sequence analysis of multiple clones generated from polymerase chain reaction (PCR)-amplified products of cDNA analogous to fragments of 5 non-coding region (5NC), envelope region 1/2 (E1/E2) and non-structural region 3 (NS3) of viral genome. Although nucleotide substitutions were more common in coding regions than in the 5NC region, there was no region corresponding to the hypervariable region of hepatitis C virus in the E1/E2 region. Transition substitution exceeded transversion by 7 to 12-fold, and 79.4% of substitutions were synonymous. This bias against substitutions producing amino acid replacements and the use of Pfu DNA polymerase with an error rate 10 times lower than the observed frequency of substitution, suggests that most substitutions were not artefactual. This data suggests that individual genomes of HGV within an infected individual may differ from each other at 0.23–0.84% nucleotide position and at 0.42–0.61% amino acid position.     

A new pseudo-peptide of Arg-Gly-Asp (RGD) with inhibitory effect on tumor metastasis and enzymatic degradation of extracellular matrix

A series of pseudo-peptide analogs of the Arg-Gly-Asp (RGD) sequence of fibronectin have been synthe-sized, and their anti-metastatic effects in mice and inhibitory effects on tumor cell invasion in vitro have been examined. The partially modified retro pseudo-peptide of RGD, R_rev-COCH₂CO-D (FC-63), was more effective in inhibiting tumor metastasis than the original RGDS peptide. Replacement of the malonyl moiety of FC-63 with a carboxyethylene linkage (R_rev-COCH₂CH₂-D, FC-303 ) achieved more potent inhibition of lung metastasis of melanoma cells than FC-63. Among the analogs, FC-336, a p-xylylendiamine derivative having two FC-303 moieties, showed the most potent inhibitory effect on experimental lung metastasis produced by i.v. co-injection with B16-BL6 melanoma or colon 26 M3.1 cells in a dose-dependent manner. Multiple administrations of FC-336 after tumor inoculation also showed efficient therapeutic potency against spontaneous lung metastasis of B16-BL6 melanoma in mice. Furthermore, FC-336 effectively inhibited the invasion, migration and adhesion of tumor cells in vitro, but its inhibitory effects were not more than those of RGDS peptide. Zymography analysis revealed that FC-336 inhibited the degradation of gelatin substrate by matrix metalloproteinases (MMPs) produced by tumor cells, while the RGDS peptide did not affect the enzymatic degradation. These findings indicate that the pseudo-peptides of the RGD sequence, possessing the inhibitory property of the degradation by MMPs differently from original RGD-containing peptides, may be advantageous and useful in preventing tumor metastasis. © Rapid Science 1998     

Peliosis Hepatis in a Child with X-Linked Myotubular Myopathy Treated with Living-Donor Liver Transplant: A Case Report

BackgroundMyotubular myopathy is a rare disease sometimes accompanied by peliosis hepatis, a leading cause of fatal liver hemorrhage.Case ReportWe present a case of a 2-year-old boy with myotubular myopathy who developed liver hemorrhage because of peliosis hepatis and was successfully treated with living-donor liver transplant. The patient initially presented with fever, anemia, and liver dysfunction. A computed tomographic scan revealed hemorrhages in the liver, and the patient underwent hepatic artery embolization twice. After the second embolization, multiple peliosis hepatis cavities appeared in the left lobe of the liver that had increased in size. Therefore, the patient underwent ABO-incompatible living-donor liver transplant using a lateral segment graft from his father. The patient developed severe septic shock with an unknown focus on postoperative day 18, which resolved with antibiotic therapy. On postoperative day 62, he was discharged. Fourteen months after undergoing living-donor liver transplant, the patient showed no recurrence of peliosis hepatis.ConclusionsAlthough the long-term prognosis of peliosis hepatis due to myotubular myopathy after living-donor liver transplant remains unclear, liver transplant may be a curative treatment for patients with myotubular myopathy who have uncontrollable peliosis hepatis.     

Outcome of advanced renal cell carcinoma arising in end-stage renal disease: comparison with sporadic renal cell carcinoma

Clinical and Experimental Nephrology - The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited. Patients diagnosed with...     

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.     

Cytotoxic properties of a new synthetic demethylpodophyllotoxin derivative,BN 58705, against human tumor cell lines

The in vitro cytotoxic properties of a newly synthesized demethylpodophyllotoxin derivative, 4-o-butanoyl-4-demethylpodophyllotoxin (BN 58705), were determined by using several human tumor cell lines of different histological origin and of different sensitivity to conventional chemotherapeutic drugs (Adriamycin andcis-diammine-dichloride platinum). BN 58705 is shown to be cytotoxic against various human tumor cell lines as assessed by the MTT assay. Furthermore, BN 58705 is shown to be cytotoxic against several drug-resistant tumor cell lines. BN 58705 is cytotoxic at concentrations 100- to 1000-fold lower than those of Adriamycin orcis-diammine-dichloride platinum required to achieve similar cytotoxicity. BN 58705 did not mediate DNA fragmentation of target cells, whereas the epipodophyllotoxin-like etoposide induced DNA cleavage by stabilizing the DNA-enzyme intermediate. Like vinca alkaloids, BN 58705 induced a block in the mitotic phase of the cell cycle. By comparison, BN 58705 exerted a stronger cytotoxic activity in vitro than did either etoposide, an epipodophyllotoxin, or vincristine, a vinca alkaloid. When BN 58705 was applied in vivo in mice, it resulted in low toxicity (50% lethal dose, 150 mg/kg). These results demonstrate than BN 58705 is cytotoxic to drug-resistant human tumor cell lines and is manyfold more potent than conventional drugs. The cytotoxic potency and low toxicity of BN 58705 are important criteria to establish its potential chemotherapeutic efficacy in vivo.Abbreviations cpm counts per minute - BN 58705 4-o-butanoyl-4-demethylpodophyllotoxin - MTT 3-(4,5-dimethyl-thiazoyl-2-yl)-2,5-diphenyl-tetrazolium bromide - OD optical density - TRIS TRIS (hydroxymethyl) aminomethane - EDTA ethylenediaminetetraacetic acid - FITC fluoresceinisothiocyanate - PI propidium iodide This work was supported by a grant from Institut Henri Beaufour, France     

Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.