Large-Scale Channel Migration in the Sittang River Estuary.

An estuary is a dynamic environment where marine and fluvial processes meet to form complex and transient morphology. The estuary morphology is largely determined by net sediment transport by two-way tidal flows, but the hydrodynamics also depends on the morphology of the tidal channels. The estuary inherently accommodates cyclic processes that are internally generated through hydro-morphodynamic interactions. In addition, the estuary evolves in response to changes in external forces by natural and anthropogenic factors. Morphological changes under the different controls often hinder the comprehension of the evolutionary processes of estuaries. Here we explored morphological changes in the Sittang River estuary, Myanmar, which has great morphological dynamism from extreme tidal energy and large sediment inputs, through field surveys and satellite imagery analysis. We identify an autocyclic process in a sedimentary system driving large-scale channel migration in decadal to multidecadal cycles. We show that drastic changes of the estuary morphology occasionally occur with rapid bank erosion through modulation of the cyclic channel migration under conflicting tidal and fluvial forces. This extreme case with minimal human intervention highlights channel migration as a key process in morphological evolution of tide-dominated estuaries undergoing active infilling.

[Liposomal local therapy of sinunasal symptoms in ANCA associated vasculitis]. / Sinunasale Symptome ANCA-assoziierter Vaskulitiden und deren Therapie mit Liposomen.

BACKGROUND: GPA, eGPA and MPA constitute the group of AAV. ENT manifestations are part of the typical clinical picture of these diseases. Usually, patients are treated with systemic immunomodulatory drugs, mostly based on organ affection. In clinical routine, an insufficient decrease of sinunasal manifestations during a solely systemic therapeutic concept can repeatedly be -observed. MATERIAL AND METHODS: Between February 2009 and November 2012, 20 patients with AAV were diagnosed in or referred to our department for further treatment. Clinical symptoms and manifestations were measured by the use of international accepted activity scores. The effect of a local therapy with liposomes for a period of 2 months on sinunasal symptoms was prospectively evaluated by using visual analogue scales and standardized questionnaires. RESULTS: Within the described collective 100% of patients did show ENT-symptoms at the time of initial diagnosis. Every patient did receive immunomodulatory therapy, but in 61.1% of cases there was just slight or no improvement on sinunasal symptoms. After a 2-month period of liposomal local therapy, a significant reduction of sinunasal complaints could be observed, both evaluated via visual analogue scales (p<0.001 to p=0.014, depending on the evaluated symptom) and standardized questionnaires (p<0.001). CONCLUSIONS: The local application of liposomes in addition to a systemic therapy is effective in alleviating sinunasal manifestations in patients with AAV.

Soft-diet feeding after weaning affects behavior in mice: Potential increase in vulnerability to mental disorders.

Mastication is one of the most important oral functions, and the period during which mastication is acquired overlaps with the term of rapid development and maturation of the neural systems. In particular, the acquisition period after weaning is related to the potential onset of mental disorders. However, the roles of mastication during this period for brain development remain largely unknown. Therefore, we used a series of standard behavioral analyses, assessment of hippocampal cell proliferation, and the expression of brain-derived neurotrophic factor (BDNF), TrkB, and Akt1 in the hippocampus and frontal cortex of mice to investigate the effects of post-weaning mastication on brain function. We fed 21-day-old C57BL6/J male mice either a hard or a soft diet for 4weeks and conducted a series of standard behavioral tests from 7weeks of age. Further, histological analysis with bromodeoxyuridine was performed to compare hippocampal cell proliferation at 7 and 14weeks of age. Real-time polymerase chain reaction was performed to compare BDNF, TrkB, and Akt1 expression in the hippocampus and frontal cortex of 14-week-old mice. Compared to mice fed a hard diet (HDM), soft-diet mice (SDM) showed behavioral impairments, including decreased home cage activity, increased open field test activity, and deficits in prepulse inhibition. These results were similar to those observed in mouse models of schizophrenia. However, no effects were observed on anxiety-like behaviors or memory/learning tests. Compared to HDM, SDM showed significantly decreased hippocampal cell proliferation and hippocampal BDNF and Akt1 gene expression at 14weeks of age. A soft diet after weaning may have resulted in histological and molecular changes in the hippocampus and influenced outcomes of behavioral tests related to mental disorders. Our findings suggest that soft-diet feeding after weaning may affect both physical and mental development of mice, and may increase vulnerability to mental disorders.

[A tongue biopsy led to the diagnosis]. / Die Diagnose liegt auf der Zunge.

A 76-year-old patient in otherwise good health presented with a 2-year history of bilateral painless submandibular swelling and macroglossia. A standard ENT examination revealed no additional symptoms. Tongue biopsy led to the diagnosis of amyloidosis, serum immunofixation identified AL amyloidosis and a kappa light chain gammopathy resulting from multiple myeloma as the underlying cause.

Gravitational unloading inhibits the regenerative potential of atrophied soleus muscle in mice.

AIM: The present study was performed to investigate the influence of unloading on the regeneration of atrophied and injured skeletal muscle. METHODS: Male mice (C57BL/6J), aged 8 weeks, were used. Cardiotoxin (CTX) was injected into soleus muscles bilaterally. Gravitational unloading on soleus muscle was performed by hind limb suspension for 2 weeks before and additionally 6 weeks after CTX injection in one group. Soleus muscles in the remaining groups were loaded keeping the mice in the cages and were dissected 14, 28 and 42 days after the injection. RESULTS: Recovery of the wet weight and protein content of soleus in the CTX-injected group was inhibited by unloading. Increase in satellite cell number, induced by CTX injection and loading, was also inhibited by unloading. Disappearance of infiltration of mononucleated cells into the necrotic area was also delayed. This phenomenon suggests that regeneration, which is indicated by the appearance of fibres with central nuclei, was inhibited by unloading. CONCLUSION: Results suggested that loading plays an important role in the activation of the regenerating potential of injured skeletal muscle.

A novel synthetic DNA minor groove binder, MS-247: antitumor activity and cytotoxic mechanism.

PURPOSE: MS-247 is a novel synthetic compound possessing a DNA-binding moiety and a DNA-alkylating residue, chlorambucil. In this study, we evaluated the antitumor activity of MS-247 against murine tumor cell lines and its effects on DNA molecules in both cell-free and cellular systems. METHODS: The in vitro cytotoxic activity of MS-247 was evaluated against four murine tumor cell lines, P388, L1210, Colon26 and B16, and its in vivo antitumor activity was also tested in comparison with Adriamycin (ADM), cisplatin (CDDP) and paclitaxel. The ability of MS-247 to associate with the DNA minor groove was assessed by measuring quenching of Hoechst 33342 fluorescence. DNA-DNA interstrand crosslinks (ICL) were detected by an alkaline elution assay for cellular DNA and a band-shift assay using the plasmid pBR322. The effects of MS-247 on macromolecule synthesis (DNA, RNA and proteins) were examined by measuring incorporation of the radiolabeled precursors. RESULTS: MS-247 exhibited in vitro cytotoxicity with IC(50) values ranging 11 to 500 nM, and MS-247 given i.v. showed strong in vivo antitumor activity against i.p.-implanted L1210 leukemia cells and s.c.-implanted Colon26 carcinoma cells, and moderate activity against i.p.-implanted P388 leukemia cells but no apparent activity against s.c.-implanted B16 melanoma cells. MS-247 reversibly displaced Hoechst 33342 bound to DNA within a few minutes, and irreversibly formed ICL within 1-6 h in both the cell-free system and the cellular system. These results suggest that an association of MS-247 with the DNA minor groove occurred more quickly than ICL formation. The inhibition of DNA synthesis was more prominent than the inhibition of RNA and protein synthesis in L1210 cells exposed to MS-247, and a 6-h incubation with MS-247, which formed apparent ICL in the cellular system, strongly inhibited DNA synthesis. This result suggests that impairment of DNA replication preceded the inhibition of RNA and protein synthesis and that ICL formation greatly contributed to the inhibition of macromolecule synthesis. CONCLUSION: The results of this study suggest that MS-247 exerts its cytotoxic effect through impairment of DNA function by getting into the minor groove of DNA and subsequently forming ICL. MS-247 has potent antitumor activity with a different spectrum from the activity of clinically proven antitumor agents such as paclitaxel, ADM and CDDP against several murine tumor cell lines. This result suggests that MS-247 may be useful for the treatment of human cancers.

Potent antitumor activity of MS-247, a novel DNA minor groove binder, evaluated by an in vitro and in vivo human cancer cell line panel.

We synthesized a novel anticancer agent MS-247 (2-[[N-[1-methyl-2-[5-[N-[4-[N,N-bis(2-chloroethyl) amino] phenyl]] carbamoyl]-1H-benzimidazol-2-yl] pyrrol-4-yl] carbamoyl] ethyldimethylsulfonium di-p-toluenesulfonate) that has a netropsin-like moiety and an alkylating residue in the structure. We evaluated antitumor activity of MS-247 using a human cancer cell line panel coupled with a drug sensitivity database and subsequently using human cancer xenografts. The average MS-247 concentration required for 50% growth inhibition against a panel of 39 cell lines was 0.71 microM. The COMPARE analysis revealed that the differential growth inhibition pattern of MS-247 significantly correlated with those of camptothecin analogues and anthracyclins, indicating that MS-247 and the two drug groups might have similar modes of action. MS-247 exhibited remarkable antitumor activity against various xenografts. A single i.v. injection of MS-247 significantly inhibited the growth of all 17 xenografts tested, which included lung, colon, stomach, breast, and ovarian cancers. In many cases, MS-247 was more efficacious than cisplatin, Adriamycin, 5-fluorouracil, cyclophosphamide, VP-16, and vincristine and was almost comparable with paclitaxel and CPT-11; these are the most clinically promising drugs at present. MS-247 was noticeably more effective than paclitaxel (in HCT-15) and CPT-11 (in A549, HBC-4, and SK-OV-3). The toxicity of MS-247, indicated by body weight loss, was reversible within 10 days after administration. The MS-247 mode of action showed DNA binding activity at the site where Hoechst 33342 bound, inhibited topoisomerases I and II (as expected by the COMPARE analysis) blocked the cell cycle at the G2-M phase, and induced apoptosis. These results indicate that MS-247 is a promising new anticancer drug candidate to be developed further toward clinical trials.

Cloning and sequencing of novel genes from Vibrio alginolyticus that support the growth of K+ uptake-deficient mutant of Escherichia coli.

Novel genes that functionally complement the growth of K+ uptake-deficient mutant strain of Escherichia coli TK420 have been cloned from the marine bacterium Vibrio alginolyticus. The nucleotide sequence revealed three open reading frames. The second gene was homologous to proC gene and allowed the growth of proC-defective mutant strain of E. coli chi 342 in the absence of proline. The first and third genes, but not proC, were required for the growth of TK420 in a synthetic medium containing 10 mM K+ and 100 mM Na+. Since K+ uptake activity of TK420 was restored by the introduction of these genes, these two genes were considered to be directly related to K+ transport. Homologous genes were found in E. coli, but their functions have not been reported.

Home program of physical therapy: effect on disabilities of patients with total hip arthroplasty.

OBJECTIVE: To study the effect of a home program of physical therapy. DESIGN: Nonrandomized control trial. SETTING: Home based. PATIENTS: Subjects had total hip arthroplasty (THA) for hip osteoarthritis (hip-OA) without THA failure, or cardiopulmonary, neurological, or cognitive problems. Twenty-three subjects (mean age 63.4 years; mean post-THA period 793 days, 6 to 48 months) were divided into 3 groups matching with age, gender, and postoperative periods. INTERVENTION: The 6-week home program included range of motion (ROM) exercises, and low resistance isometric and eccentric exercises of hip abductors. Physical therapists prescribed ROM and isometric exercises for group A, all programs for group B, and no programs for the control group. The programs were modified every 2 weeks as necessary. MAIN OUTCOME MEASURE: Hip ROM, maximum isometric hip abduction torque measured by Cybex II, gait speed, and cadence were evaluated. RESULTS: The practice ratio of the program was about 70% for both groups. Maximum isometric torque improved in the THA side of group A (p < .01) and the control group (p < .05), and on both sides in group B (p < .01). Gait speed and cadence also improved significantly. No correlation coefficient existed between practice days and the improvement ratio of the maximum torque. CONCLUSION: The home program was effective in long-term post-THA.

N-terminal quarter part of tetracycline transporter from pACYC184 complements K+ uptake activity in K+ uptake-deficient mutants of Escherichia coli and Vibrio alginolyticus.

In an attempt to clone a gene encoding the K+ uptake system from Vibrio alginolyticus, two plasmids, pKT2 and pKT4, were derived from pACYC184. These plasmids allowed the growth of K+ uptake-deficient mutant strains of Escherichia coli TK420 and V. alginolyticus FS181 in a low K+ medium. The pKT2 and pKT4 had an insertion about 7 and 6 kb, respectively, from the genome of V. alginolyticus. We prepared deletion plasmids from both plasmids and found that the site of genes inserted in the two was not identical and that the active locus corresponded to the structural gene encoding the N-terminal quarter part of tetA(C) gene. The N-terminal region of tetA(C) gene was ligated in another vector plasmid pHG165 to produce pHGK23. pHGK23 complemented the growth of TK420 in the low K+ medium. It contained only 62 bp from the genome of V. alginolyticus, and the open reading frame was composed of 98 amino acid residues from the N-terminal quarter part of tetA(C) and 5 amino acid residues attached by gene fusion. Using the Na+ -loaded cells of TK420, pHGK23 was found to increase the activity of K+ uptake. These results show that the N-terminal side tetA(C) gene product functions as a K+ uptake system.

Cloning and sequencing of a K+ transport gene (trk A) from the marine bacterium Vibrio alginolyticus.

A gene has been cloned from the marine bacterium Vibrio alginolyticus that functionally complements a mutant strain of Escherichia coli, TK420, defective in K+ transport genes (kdpABC, trkD, trkA). The cloned Vibrio gene allowed TK420 to grow in a synthetic medium containing less than 10 mM K+ and concomitantly led to an increase in K+ uptake activity. The nucleotide sequence of the cloned fragment revealed an open reading frame, which encodes a protein with a predicted 458 amino acid sequence and molecular mass of 50,122 Da. This gene has 71% homology to trkA gene at the DNA level from E. coli and the deduced amino acid sequence is 79% identical with E. coli TrkA, implying that V. alginolyticus has a trkA-like gene as a component of K+ transport systems.