Molecular assembly and gelating behavior of didodecanoylamides of alpha,omega-alkylidenediamines.
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Biomedical subjects
Publications and source records attributed to T Handa.
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Resonance energy transfer involving tryptophan as a donor and anthrylvinyl-labeled phosphatidylcholine (AV-PC), 3-methoxybenzanthrone (MBA) and 8-anilino-1-naphthalene sulfonic acid (ANS) as acceptors has been examined to obtain information on the structure of peptide-lipid systems consisting of 18A or Ac-18A-NH(2) peptides and large unilamellar phosphatidylcholine vesicles. The lower and upper limits for the tryptophan distance from the bilayer midplane have been assessed in terms of the models of energy transfer in two-dimensional systems, taking into account orientational effects. Evidence for the existence of preferential orientations of Ac-18A-NH(2) with respect to the lipid-water interface has been obtained.
Cholesteryl ester, along with triglyceride (TG), is the major core component of plasma lipoproteins. We investigated the effect of core composition on the physical state and metabolic behavior of lipid emulsions, as model particles of lipoproteins. Fluorescence studies using 1,6-diphenylhexatriene analogs showed that although cholesteryl oleate (CO) significantly decreased core mobility, the surface rigidity of phosphatidylcholine (PC) monolayers was independent of core composition. When intravenously injected into rats, the increased amount of core CO tended to retard TG emulsion removal from plasma, and the initial clearance rate was correlated with the amount of apolipoprotein E (apoE) bound from plasma. In addition, PC liposomes with a similar emulsion particle size showed negligible binding of apoE and were cleared at a slower rate compared to all emulsions. Furthermore, the effect of CO on the binding behavior of apoE to the emulsion surface and the emulsion uptake by hepatocytes was assessed in vitro. Replacing core TG with CO was found to decrease the apoE binding capacity to emulsions markedly without changing the binding affinity and thereby to reduce the cell uptake of emulsion particles by HepG2 cells. These results indicate that the physical state of core lipids, which can be modulated by CO content, plays a role in emulsion metabolism through the alteration in apoE binding.
Proton permeation rates across membranes of a synthetic branch-chained glycolipid, 1,3-di-O-phytanyl-2-O-(beta-D-maltotriosyl)glycerol (Mal3(Phyt)2) as well as a branch-chained phospholipid, diphytanoylphosphatidylcholine (DPhPC) were lower than those of straight-chained lipids such as egg yolk phosphatidylcholine (EPC) by a factor of approximately 4 at pH 7.0 and 25 degrees C. To examine whether degrees of water penetration and molecular motions in Mal3(Phyt)2 membranes can account for the lower permeability, nanosecond time-resolved fluorescence spectroscopy was applied to various membranes of branch-chained lipids (Mal3(Phyt)2, DPhPC, and a tetraether lipid from an extremely thermoacidophilic archaeon Thermoplasma acidophilum), as well as straight-chained lipids (EPC, 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), and digalactosyldiacylglycerol (DGDG)) using several fluorescent lipids. Degrees of hydration of glycolipids, Mal3(Phyt)2, and DGDG were lower than those of phospholipids, EPC, POPC, and DPhPC at the membrane-water interfaces. DPhPC showed the highest hydration among the lipids examined. Meanwhile, rotational and lateral diffusive motions of the fluorescent phospholipid in branch-chained lipid membranes were more restricted than those in straight-chained ones. The results suggest that the restricted motion of chain segments rather than the lower hydration accounts for the lower proton permeability of branch-chained lipid membranes.
The effects of the acyl chain composition of phosphatidylcholines (PCs) on the stability of small unilamellar vesicles during freeze-drying and rehydration in the presence of maltose were studied by monitoring the retention of a trapped marker, calcein, in the internal liposome compartment. In dipalmitoyl PC, beta-oleoyl-gamma-palmitoyl-PC and egg yolk PC liposomes, good or fair retentions (>50%) were observed in the presence of maltose, but maltose was ineffective in preserving retention in the dioleoyl PC (DOPC) liposomes (<10%). The extremely low retention in the DOPC liposome was ascribed to neither a formation of the inverted hexagonal phase of the liposomal membrane nor the fusion/aggregation of the liposomes in the drying-rehydration process. Differential scanning calorimetry measurements suggested that interactions of maltose with PC headgroups were essential to stabilizing the dry liposomes. These interactions were significant in the saturated or mixed chain liposomes but were markedly reduced in the DOPC liposomes.
Giant serpentine aneurysms (GSAs) are defined as partially thrombosed giant aneurysms with persistent serpentine vascular channels. Surgical management of these rare lesions is difficult because of their large size, complex structure, and unique hemodynamics. The authors report two cases of patients harboring GSAs with mass effect, which were managed effectively with endovascular treatment. The first patient was a 48-year-old man who presented with left homonymous hemianopsia caused by a GSA involving the terminal portion of the right internal carotid artery. The second patient, a 10-year-old boy, presented with tetraparesis from compression of the cervicomedullary junction by a GSA of the right vertebral artery. In each case, after confirming collateral flow by temporarily occluding the proximal artery, the aneurysm was trapped by placement of Guglielmi detachable coils at the sites at which the serpentine channels entered and exited the aneurysm. The midportion of each channel was isolated completely without packing, to maximize resorption of the devascularized mass. Mass effect and clinical symptoms rapidly improved in both cases, with no associated morbidity. We recommend endovascular trapping as a safe and effective therapeutic option for GSAs.
A 25-year-old man was admitted to our hospital because of hematuria, anemia and thrombocytopenia. Laboratory examinations revealed an increased number of bone marrow megakaryocytes and an increased level of platelet-associated immunoglobulin G, suggesting immune thrombocytopenia. Computed tomography of the abdomen showed enlargement of the bilateral kidneys with multiple low-density areas, although neither lymphadenopathy nor hepatosplenomegaly was evident. After amelioration of the thrombocytopenia by prednisolone therapy, open renal biopsy was performed and a diagnosis of diffuse large B-cell non-Hodgkin's lymphoma was made. The patient achieved complete remission after CHOP therapy. This was thought to be a rare case of primary renal non-Hodgkin's lymphoma initially presenting as immune thrombocytopenia, which was treated successfully by chemotherapy.
The usefulness of a mutant of Escherichia coli enterotoxin for the induction of cellular immunity to varicella-zoster virus as a mucosal adjuvant is assessed in mice. When a commercially available live varicella vaccine (the Oka strain) and toxin were once administered simultaneously via the nasal route, delayed-type hypersensitivity to Oka vaccine virus was significantly induced and detected by footpad test in mice. Moreover, when spleen cells from mice immunized with the vaccine and toxin were re-stimulated with live vaccine in vitro, they showed more thymidine uptake and produced more IL-2 than those from mice immunized with the vaccine alone. These results suggest that mutant enterotoxin has adjuvant action to induce a specific delayed-type hypersensitivity to Oka vaccine virus on nasal co-administration with live vaccine virus.
A total of 11 independent beta-glucuronidase (GUS) positive hairy roots were induced following co-cultivation of leaf explants of Antirrhinum majus L. with Agrobacterium tumefaciens strain GV2260 containing rol-type multi-auto-transformation (MAT) vector pNPI702. A total of 326 adventitious shoots were regenerated from the hairy root lines on 1/2 MS medium without plant growth regulators at 25 degrees C under a 16 h/day photoperiod condition 4 months after infection of the A. tumefaciens GV2260. The absence of the rol genes in five plants was verified by polymerase chain reaction (PCR) and Southern blot analysis. Acclimatized transformants exhibited normal phenotypes in height and in the morphology of leaves and flowers. Furthermore, the GUS gene was strongly expressed in the leaves, inflorescence of the transformed plant, and the progeny. This result demonstrates that the rol-type MAT vector can be used to study gene functions controlling the morphogenesis of Antirrhinum majus plants.
We have recently shown that sphingomyelin (SM) strongly inhibits lipoprotein lipase (LPL)-mediated lipolysis in monolayers and emulsion particles. To further evaluate how SM modulates LPL activity on the emulsion surface, the relationship between membrane surface structure and LPL activity was investigated. We measured fluorescence anisotropy of 1-palmitoyl-2-[3-(diphenylhexatrienyl)propionyl]-sn-3-phosphati dylcho line, probing surface acyl chain fluidity, and fluorescence lifetime of N-(5-dimethylaminonaphthalene-1-sulfonyl)dipalmitoylphosphatidylethan olamine in H(2)O and D(2)O buffer, assessing the degree of hydration in the head group region. The results revealed that incorporation of egg SM into triolein-egg phosphatidylcholine emulsions markedly increased acyl chain order and decreased head group hydration of the surface monolayers. In contrast, cholesterol was shown to increase head group hydration despite a strong increase in acyl chain order. The close correlation between the apparent K(m) values of LPL and the degree of head group hydration indicated that LPL interacts with the head group region rather than with the hydrophobic interior of the surface monolayers. However, apparent V(max) did not show a simple correlation with any surface structure, and the finding in which SM had no effect on apparent V(max) of medium-chain triglyceride emulsions suggested that the hydrophobic interaction between acyl chains of SM and triglyceride at the emulsion surface is important for determining the apparent V(max). These results showed conclusively that SM inhibits LPL activity mainly by changing the emulsion surface structure and not by a specific interaction between SM and LPL.
The possibility of radiographically diagnosing carcinoma with submucosal involvement (invasive carcinoma) is discussed based on 119 invasive carcinomas of the large bowel that had been treated surgically and colonoscopically over a period of 9 years (1989-1997) at the Cancer Institute Hospital in Tokyo. Of these lesions, 38 were superficial-type invasive carcinoma, accounting for 31.9% (38/119) of all invasive colorectal carcinomas, including 36 lesions (94.7%, 36/38) of types IIa and IIa + IIc and 2 lesions (5.3%, 2/38) of type IIc + IIa. No pure type IIc was seen. The radiographic images obtained were correlated with macroscopic findings and analyzed in terms of visualization of the lesion's contour, central depression, converging folds, and basal indentation. A definitive diagnosis of superficial invasive carcinoma can be made radiographically if a lesion measures 10 mm and reveals moderate to severe basal indentation in a complete or nearly complete profile radiographic image. Attention should be paid to the presence of superficial-type advanced carcinomas measuring 10 mm or less, which is not infrequently experienced in Japan. Polypoid invasive carcinoma can be definitively diagnosed in the same way with much more certainty than can the superficial type because few polypoid advanced carcinomas are less than 20 mm. The size and the radiographic sign of the basal indentation are the most important indicators for the diagnosis of invasive carcinoma.
Although it has been reported that intravenous injection of Escherichia coli enterotoxin induces atrophies of the thymus and spleen by necrosis, the toxin injected intramuscularly to mice induced atrophies of both tissues, which were associated with apoptosis of lymphocytes. Apoptosis predominantly occurred in the thymus and increased in a time-dependent manner up to 26 h and faint ladder band patterns of DNA were observed at 36 h. Although the high dose of toxin also induced in vitro apoptosis in cultured thymocytes, the toxin was not detected in the serum at levels sufficient to cause in vitro apoptosis after intramuscular administration. By flow cytometric analysis, CD4+ CD8+ double-positive T cell and CD45+ positive B cell numbers were found to be mainly decreased in thymus and spleen, respectively, of mice. These results suggest that the atrophies of thymus and spleen by intramuscular administration of the toxin to mice are due to apoptosis of CD4+ CD8+ double-positive T and CD45+ positive B cells, respectively, but the toxin does not reach these cells via the circulation. A different mechanism from that in vitro in cultured cells might be involved in the induction of apoptosis in vivo.
Abnormal hepatic haemodynamics and function in a 43-year-old woman with hereditary haemorrhagic telangiectasia (HHT) were evaluated using 99Tcm-phytate angiography and iodine-123-iodoamphetamine transrectal portal scintigraphy. Radionuclide angiography demonstrated hyperdynamic perfusion of the liver owing to intrahepatic arteriovenous fistulae (AVF), entry of tracer into the systemic circulation through intrahepatic portosystemic shunts and an increase in recirculating blood flow caused by these vascular disorders. Heterogeneous distribution of tracer also suggested the presence of chronic hepatic injury. Transrectal portal scintigraphy showed large portosystemic shunts. Other imaging techniques confirmed the presence of the AVF but failed to identify the portosystemic shunts. Non-invasive radionuclide studies are helpful in the evaluation of hepatic involvement of HHT.
We used the CAG regimen (low-dose cytarabine [10 mg/m2 per 12 hours, days 1-14], aclarubicin [14 mg/m2 per day, days 1-4], and granulocyte colony-stimulating factor [200 micrograms/m2 per day, days 1-14]) for the treatment of patients with primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation (RAEB-T) in addition to relapsed AML. Forty-three of 69 (62%) patients achieved complete remission (CR), including 29 of 35 (83%) patients with relapsed AML, 1 of 8 patients with primary resistant AML, 5 of 8 elderly patients with previously untreated AML, and 8 of 18 patients with previously untreated secondary AML or RAEB-T. Ten of 22 (45%) patients > or = 65 years old achieved CR. The patients who achieved CR received at least 1 course of modified CAG therapy as the first consolidation therapy, followed by various second consolidation and intensification therapies. The median disease-free survival and overall survival were 8 and 15 months, respectively, for relapsed AML; 11 and 8 months for the elderly patients; and 8 and 17 months for secondary AML and RAEB-T. Myelosuppression was mild to moderate, and other than fever, severe nonhematologic toxicity was rare. CAG as the induction therapy seems promising for the treatment of various categories of poor-prognosis AML.
We report a rare case of hypereosinophilic syndrome (HES) that developed to acute myeloblastic leukemia (AML). The patient, a 34-year-old man, presented with eosinophilia of unknown origin (white blood cells 38,200/microliter with 74% eosinophils) and pericardial effusion, and was diagnosed as having HES with a normal karyotype. He received four cycles of combination chemotherapy including cyclophosphamide, cytosine arabinoside and vindesine, and thereafter remained in remission. After 12 years, he was referred to our hospital because of fever and malaise. On admission, CBC showed white blood cells 3,000/microliter with 70% myeloblasts and 3% eosinophils. The bone marrow was hypercellular with 95% blasts, which were negative for myeloperoxidase (MPO) staining. Immunophenotype analysis revealed that the cells were positive for CD13, CD19, CD34, HLA-DR and cytoplasmic MPO. CD19-positive AML was diagnosed. Cytogenetic analysis showed 46, XY, t(6;21)(q13;q22), add(7)(q11) in 19 of 20 metaphase spreads. Rearrangement of the AML1 gene at 21q22 and fusion of the BCR/ABL gene could not be detected by fluorescence in situ hybridization analysis. The patient received combination chemotherapy and achieved a complete remission. Chromosome aberrations involving 7q as well as 21q22 suggested that the initial chemotherapy for HES might have been implicated in the pathogenesis of acute leukemia in this case.
Lipid emulsions, triacylglycerol droplets covered with single surface monolayers of phospholipid in aqueous medium, were prepared by high-pressure emulsification and successive ultracentrifugation. Egg yolk phosphatidylethanolamine did not stabilize triolein (TO) droplets in aqueous medium. Phosphatidylcholine (PC) of various long fatty acyl chains dispersed TO and tricaprylin (TC) well in aqueous medium as emulsion droplets of 110 nm. After ultracentrifugation, however, oil separation was observed in the floating creamy layer of TO/dioleoyl-PC emulsions. Dioleoyl-PC contains two bulky unsaturated fatty acyl chains, as well as oleoyl chains, and it has a lower spontaneous curvature than egg PC. Egg PC and dipalmitoyl-PC gave stably dispersed emulsion droplets of TO even after the freeze-thawing (F-T) procedure. On the other hand, TO/egg PC emulsion droplets containing cholesterol of 83 mol% PC and TC/egg PC emulsion droplets coalesced after the F-T procedure. Cholesterol and a medium chain triacylglycerol, TC, were distributed into the surface PC monolayers and occupied an appreciable fraction of the surface area. These neutral lipids have small polar groups and thus decrease the mean spontaneous curvature of surface lipids. The relationship between the droplet coalescence and the spontaneous curvature was discussed on the basis of the coalescence transition state theory recently developed by Kabalnov et al. in 1996. In addition, effects of maltose on the emulsion coalescence in the freeze state were briefly discussed. Copyright 1999 Academic Press.
OBJECTIVE: To investigate biomechanical determinants and predictors of walking speed in early gait training after stroke. DESIGN: Prospective. SETTING: Physical therapy room of Tohoku University Hospital. PARTICIPANTS: Thirty-four male hemiparetic stroke patients received 8 weeks of computer-assisted gait training (CAGT), which was initiated within approximately 3 months after stroke onset. MAIN OUTCOME MEASUREMENTS: The time and the number of steps required to walk 10m at the fastest possible speed (maximum walking speed [MWS]), the sway path of the center of feet pressure (CFP) in the upright posture, the change in CFP when shifting the body weight either left to right or back and forth, and the maximal isokinetic muscle strength during extension of both knees were measured at the start and at 4 and 8 weeks. Stepwise regression procedures were performed to analyze determinants and predictors of the MWS using the MWS as the dependent variable and personal characteristics, standing balance, and the muscle strength of both knees as the independent variables. RESULTS: The MWS significantly increased from 40.4 to 76.5m/min on average after 8 weeks. The determinant of MWS at the start was the postural control of shifting to the left and right (coefficient of determination of 45.4%). The determinant of MWS at 4 and 8 weeks was the muscle strength during knee extension on the affected side (coefficient of determination of 62.9% and 54.5%, respectively). The predictors of MWS at 4 weeks were the MWS at the start of CAGT, followed by muscle strength during knee extension on the affected side and the time from stroke onset to the start of CAGT (total variance of 84.3%). The predictors at 8 weeks were the MWS at the start, followed by the muscle strength during knee extension on the affected side (total variance of 73.4%). CONCLUSIONS: After 4 weeks, the biomechanical determinant of MWS had changed from the postural control of weight-shifting from left to right to the muscle strength during knee extension on the affected side. The MWS at 4 and 8 weeks could be predicted by the initial MWS, the initial muscle strength during knee extension on the affected side, and the time since stroke onset, with high coefficients of determination.
BACKGROUND: To evaluate whether tumor markers can be used to assess response to systemic chemotherapy, we analyzed preliminarily the relationship between the response to chemotherapy based on serial imaging and on change in serum tumor marker level of CEA, CA19-9 and CA125. METHODS: We analyzed 26 patients with advanced gastric cancer in whom at least one of the tumor markers CEA, CA19-9 and CA125 was elevated before systemic chemotherapy with regard to the relationship between the change in serum tumor marker level and response assessment by imaging studies throughout the treatment course. A responder was defined as showing a > or = 50% drop in tumor marker level for more than 4 weeks. RESULTS: The sensitivity and negative predictive value of falling tumor marker level after chemotherapy for a partial response in imaging was 100%. When patients were categorized as responders or non-responders, a significant correlation was observed between the assessment of response by tumor markers and by imaging studies. The survival time of responders assessed by tumor markers was significantly longer than that of non-responders. CONCLUSIONS: The measurement of tumor markers might be useful in monitoring response and in predicting the prognosis of patients with advanced gastric cancer treated with systemic chemotherapy. Tumor markers may be used as a means of monitoring treatment in patients when in an imaging study it is difficult to assess response to chemotherapy in clinical practice. Further studies are required to confirm these findings.