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Biomedical subjects

Y Wada

Publications and source records attributed to Y Wada.

At least 613 records · Page 34Linked to original sources

[Clinical evaluation of anticancer effect of methionine-depleting total parenteral nutrition with 5-fluorouracil and/or mitomycin C].

Methionine-depleting total parenteral nutrition (Met-deplete TPN), infusing AO-90 amino acid solution (lacking both L-methionine and L-cysteine) as a sole nitrogen source, showed synergistic effects with several antineoplastics including 5-fluorouracil (5-FU). In the recent multi-center, randomized, controlled study, advanced gastric cancer patients were randomly allocated to RT group and Control group. RT group received AO-90 amino acid solution, while Control group infused Amiparen (commercial methionine and cysteine containing amino acid solution) as protein source for 14 days' TPN with 5-FU and mitomycin C (MMC). The over all clinical response rate (PR+CR) in RT and Control groups were 26.3% and 8.1%, respectively, with significant statistical difference in both values at p = 0.015. Fourteen advanced gastric cancer patients allocated to RT and Control group randomly and received each amino acid as protein source for 7 days TPN with 5-FU administration. All cases were performed gastrectomy without waiting period, and resected material was examined the histological response. In the 7 cases of RT group, grade 2 was seen in 4 cases, grade 1-b in 1, grade 1-a in 1 and grade 0 in 1. In the 7 of Control, 3 cases were grade 1-a and the remaining 4 were grade 0. There were significant differences in both degree and incidence of the histological response at p = 0.016. A stage IV gastric cancer patient with marked liver metastasis received 2 times RT therapy with 5-FU and MMC for 14 days and undertaken gastrectomy after 22 day, waiting period. Resected gastric cancer showed grade 2 to 3 histological response, and the liver metastasis showed marked effect as PR to CR.

Amino Acids↗

Facilitation in Anopheles and spontaneous disappearance of filariasis: has the concept been verified with sufficient evidence?

The validity of recently much argued phenomenon of facilitation in the transmission of filariasis was considered by examining previously published papers. It was concluded that there was no clear evidence to support the existence of facilitation and facilitation-based unstable equilibrium in relation to microfilaria prevalence and density in human population below which filariasis would spontaneously disappear, even when the vector was Anopheles mosquitoes. Instead, the existence of a critical level of man/mosquito contacts for the disappearance of filariasis was suggested.

Animals↗

[Sex-related differences in EEG coherence in normal young adults--evaluation during rest and photic stimulation].

EEG coherence is a noninvasive technique for studying functional relationships between brain regions. Although EEG coherence would be a useful method to explore the differences in cerebral functional organization between the sexes, sex differences in coherence have not been well documented. The present study was conducted therefore to examine sex differences in interhemispheric EEG coherence during rest and photic stimulation (PS) in 15 male and 15 female healthy young adults. Interhemispheric coherence of the resting EEG revealed no significant sex differences for any frequency band. In contrast, coherence during PS revealed significant sex differences, and the females had a significantly higher coherence than the males in the frequency band (4.5-5.5Hz) corresponding to 5Hz PS. In addition, the changes in interhemispheric coherence from rest to the stimulus condition (i.e., coherence reactivity) showed sex differences at the brain region primarily involved in visual functioning; the females had significantly greater coherence reactivity for O1-O2 in EEG during PS at 5 and 15Hz. These findings indicate sex differences in interhemispheric EEG coherence during PS, and provide further evidence that sex-related differences exist in the degree of lateralization of hemispheric function.

Adult↗

[Sex differences in EEG background activity: a study with quantitative analysis in normal adults].

The present study performed quantitative EEG analysis in normal 20 males and 20 females, aged 18-26 years, in order to examine the sex differences in EEG activity at rest. The females had more absolute EEG power than the males, with significant differences observed for delta, theta and beta bands. In contrast, no significant difference was found in peak alpha frequency or relative EEG power for any frequency band. The present findings provide further evidence that females have more absolute power in resting EEG, and emphasize the importance of matching patients and control populations for sex in future investigations dealing with the relationship between resting EEG and various pathological conditions.

Adolescent↗

Detection of donor lymphocytes in the cerebrospinal fluid of a patient with metachromatic leukodystrophy following bone marrow transplantation.

An unrelated donor bone marrow transplant (UD-BMT) was carried out on a 10-year-old patient with metachromatic leukodystrophy (MLD). We collected cerebrospinal fluid (CSF) on day +168 and cultured it with recombinant IL-2 and PHA-P to examine the origin of cells in the CSF. Analysis on variable number of tandem repeat (VNTR) of lymphocytes in the CSF amplified by PCR revealed that lymphocytes in the CSF were of donor origin. These data support that BMT at an early stage may prevent deterioration in MLD. Although the patient developed grade III acute GVHD with rash and diarrhea, we successfully treated acute GVHD using rabbit anti-human thymocyte immunoglobulin (ATG). UD-BMT may be an alternative treatment for patients with MLD in the absence of an HLA matched family donor.

Bone Marrow Transplantation↗

Closure of leaks by fibrin gluing. Effects of various application techniques and temperatures.

This study was performed to determine the differences in covering power obtained with fibrin gluing using three different methods, layered, mixing, and spraying. The experimental system consisted of a 2 x 2 cm plastic plate with a hole 1 mm in diameter, a plastic syringe, and a digital manometer. The internal pressure of the syringe barrel was measured with the digital manometer. Five minutes after fibrin glue membranes (1 mm in thickness) had been prepared on the plastic plate with the layered, mixing, or spray method, the plunger of the syringe was pushed slowly, and the maximum internal pressure in the syringe barrel was measured, just before the breakage of the membrane. Experiments were performed five times at each four temperatures, 12 degrees C, 17 degrees C, 22 degrees C and 37 degrees C. Covering power of fibrin glue membranes (units: mmHg; atmospheric pressure 760 mmHg) were as follows: 1) Layered method (12 degrees C: 810.0 +/- 68.6, 17 degrees C: 769.0 +/- 10.2, 22 degrees C: 812.0 +/- 112.4, 37 degrees C: 773.6 +/- 24.4). 2) Mixing method (12 degrees C: 956.6 +/- 219.3, 17 degrees C: 972.4 +/- 243.5, 22 degrees C: 1045.2 +/- 233.0, 37 degrees C: 1059.0 +/- 220.2). 3) Spray method (12 degrees C: 1010.0 +/- 231.1, 17 degrees C: 1144.4 +/- 170.6, 22 degrees C: 1148.0 +/- 234.7, 37 degrees C: 1250.0 +/- 111.8).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

[Renal autotransplantation for dissecting aneurysm].

Out of twenty-five patients operated on for dissecting aneurysm in our institution since January 1991, four patients had autotransplantation of the kidney. The renal autotransplantation and the segmental replacement of the descending aorta with the prosthesis were done at the same time in three of them, and segmental replacement of the distal aortic arch was followed by autotransplantation because of the postoperative acute renal failure in the other one. Postoperative renal function of simultaneously operated patients was good whereas the patient who had been treated by two-staged operation needed hemodialysis for two weeks after the autotransplantation. Postoperative scintigraphy showed fully recovered function of the autotransplanted kidneys with enlargement. CT scan showed that the false lumen of the dissecting aorta was reduced in size with increased intraluminal clot formation. Renal autotransplantation with entry closure is easy and safe technique and assures successful operative results for the dissecting aneurysm, restoring impaired renal blood flow.

Acute Kidney Injury↗

[An adult case of bacterial meningitis caused by penicillin-resistant Streptococcus pneumoniae].

Recently the incidence of infectious diseases caused by penicillin-resistant Streptococcus pneumoniae (PRSP) is increasing. Patients with meningitis caused by PRSP have been reported with high mortality especially in the field of pediatrics, and it is crucial to treat with accurate and precise choice of antibiotics. We report the first adult case of bacterial meningitis caused by PRSP in Japan. A 32-year-old male without immunological abnormalities developed acute pneumococcal meningitis. Empiric therapy with ampicillin and cefotaxime was not effective and the S. pneumonia from CSF showed resistance to multiple antibiotics such as penicillin and cefotaxime. He was treated successfully with the combination of panipenem/betamipron, vancomycin, and chloramphenicol. We assume that panipenem/betamipron is recommended to be added to empiric therapy of bacterial meningitis, considering an increasing incidence of PRSP infection.

Adult↗

[Cystinosis].

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Cystinosis↗

[Folic acid].

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Adult↗

Laboratory evaluation of a juvenile hormone mimic, pyriproxyfen, against Chironomus fusciceps (diptera: chironomidae).

The efficacy of the insect growth regulator, pyriproxyfen, against Chironomus fusciceps was examined in the laboratory. A series of 6 concentrations (0.1-0.00001 ppm) was used. A positive relationship between mortality and concentration was observed in the pupal stage as well as in the larval stage. Pyriproxyfen caused 50 and 90% emergence inhibition of C. fusciceps at 0.00177 and 0.05369 ppm, respectively.

Animals↗

Lupus anticoagulant autoantibody induces apoptosis in umbilical vein endothelial cells: involvement of annexin V.

The effects of lupus anticoagulant (LAC) on cultured human umbilical vein endothelial cells were studied. All five monoclonal antibodies from a patient with systemic lupus erythematosus (SLE), as well as plasma samples with LAC activity from six SLE patients, induced apoptosis. Anti-annexin V IgG also induced apoptosis. Since monoclonal antibodies and plasma from SLE patients had an affinity for annexin V, an endothelial apoptosis pathway mediated by annexin V was suggested as the molecular pathogenesis of the hemostatic derangement associated with LAC.

Animals↗

A correlation between thrombotic disease and a specific fibrinogen abnormality (A alpha 554 Arg-->Cys) in two unrelated kindred, Dusart and Chapel Hill III.

For the first time, a correlation between a specific fibrinogen abnormality and the clinical symptoms of thrombosis has been found in unrelated families. These abnormal fibrinogens have been designated Dusart and Chapel Hill III. The abnormal fibrinogen Chapel Hill III was identified previously in a patient with thrombotic disease. We purified fibrinogen from small aliquots of patient and normal plasmas by a simple, rapid procedure. Coomassie stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis demonstrated that fibrinogen Chapel Hill III contained several high molecular weight forms in addition to the two forms seen with normal fibrinogen. Immunoblot analysis of Chapel Hill III fibrinogen demonstrated that essentially all the high molecular weight forms react with antiserum to albumin. Immunoblot analysis of plasmin digests of Chapel Hill III fibrinogen demonstrated that albumin is linked to the C-terminus of the A alpha chain. Using DNA analysis, we found that the patient is heterozygous for a single base change, resulting in the substitution A alpha Arg 554-->Cys. This is the same change identified in fibrinogen Dusart. The Dusart family members who are heterozygous for this substitution also suffer from recurrent thrombotic disorders.

Afibrinogenemia↗

The histidine interruption of an alpha-helical coiled coil allosterically mediates a pH-dependent ligand dissociation from macrophage scavenger receptors.

Macrophage scavenger receptors uptake modified low density lipoproteins (LDLs) through receptor-mediated endocytosis. In the alpha-helical coiled coil domain, 2 histidines (His168 and His260) disrupt leucine or isoleucine heptad repeats. Substitution of His168 or/and His260 to leucine had no effect on AcLDL binding activities. However, the His260-replaced receptors had their ligand degradation activities diminished. Cell surface ligand release experiments under acidic pH clarified that His260 mutants lost their ligand dissociation activities at 37 degrees C. Furthermore, immunoelectron microscopic experiments using anti-scavenger receptor antibody showed that the His260 replaced receptors were not able to release gold-labeled AcLDL in endosomes. Here we propose an allosterical ligand dissociation mechanism by His260 in macrophage scavenger receptors.

Allosteric Regulation↗

Glycation of human beta 2-microglobulin in patients with hemodialysis-associated amyloidosis: identification of the glycated sites.

beta 2-Microglobulin (beta 2M) is a major component forming amyloid deposits in patients with hemodialysis-associated amyloidosis (HAA), a serious complication of long-term hemodialysis. Recently, we demonstrated that beta 2M modified with the Maillard reaction is a definite constituent of amyloid deposits in patients with HAA. Our further study demonstrated that this modified beta 2M induces not only chemotaxis of monocytes but also secretion of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 from macrophages, suggesting the potential link of glycation of beta 2M by the Maillard reaction to the pathogenesis of HAA. The present study was undertaken to identify the glycated site(s) of beta 2M purified from long-term hemodialysis patients as well as beta 2M incubated with glucose in vitro. Borotritide-treated beta 2M was cleaved by endoproteinase Lys-C, and peptides were isolated by reverse-phase high-performance liquid chromatography, followed by amino acid sequence analysis and fast atom bombardment mass spectrometry to identify the glycated site. The glycated sites of beta 2M formed in vivo were found to be almost the same as those of glycated beta 2M in vitro. The primary glycated site was the alpha-amino group of the amino terminal isoleucine. Other minor sites were the epsilon-amino groups of Lys-19, -41, -48, -58, -91, and -94. Computer graphics of the three-dimensional structure of beta 2M suggested that the high specificity for the glycated site at Ile-1 may be explained by its high solvent accessibility and the nearby imidazole group of His-31 as an acid-base catalyst of the Amadori rearrangement.

Adult↗

Sterol mediated regulation of SREBP-1a,1b,1c and SREBP-2 in cultured human cells.

Under conditions of cholesterol depletion and SREBP-1 accumulation, changes in the levels of sterol regulatory element binding protein(s) (SREBPs) and sterol regulated gene mRNA were studied in Hep G2 cells by RNase protection assay. Cholesterol depletion increased the expression of mRNAs for cholesterol biosynthetic enzymes and low density lipoprotein (LDL) receptor. mRNAs levels for SREBP-1c and SREBP-2 were also increased by the cholesterol depletion. In contrast, levels for SREBP-1a and 1b (1a/b) mRNA increased transiently and then decreased. To examine the effect of SREBP-1 accumulation, Hep G2 cells were incubated with a SREBP-1 degradation inhibitor, N-acetyl-leucyl-leucyl-norleucinal (ALLN). The ALLN treatment increased the LDL receptor mRNA significantly, and also increased mRNA levels for HMG-CoA reductase, SREBP-1a/b and SREBP-2. The mRNA level for squalene synthase was not changed, and for SREBP-1c was decreased by the treatment. In conclusion, the regulation of differential expression of SREBP mRNA may be involved in sterol mediated regulation of gene expression. Moreover, the regulation of the SREBP-1 level may be a critical step in the regulation of sterol mediated LDL receptor expression.

Amino Acid Sequence↗

Therapeutic effects of imidazolineoxyl N-oxide against endotoxin shock through its direct nitric oxide-scavenging activity.

We recently found a new class of nitric oxide (NO) antidote, i.e., 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide derivatives (PTIOs). It has a potent inhibitory action against endothelium-derived relaxing factor. Here, we report the effect of a water-soluble carboxy derivative of PTIO (carboxy-PTIO) on endotoxin shock. Endotoxin [lipopolysaccharide (LPS)] (10 mg/kg) was injected into Wistar rats, and the mean arterial blood pressure (MABP), heart rate and urinary parameters were continuously measured. The MABP and urine volume gradually decreased during 1 hr after LPS injection, and within 4 hr, both values decreased to 50-70%. When carboxy-PTIO at 0.056-1.70 mg/kg/min was infused for 1 hr beginning 90 min after the LPS injection, the hypotension, renal dysfunction and survival rate were much improved and the state of shock was avoided. Carboxy-PTIO administered to normal rats did not affect each parameter. Measurement of urinary output of carboxy-PTIO and carboxy-2-phenyl-4,4,5,5-tetramethylimidazole-1-oxyl (carboxy-PTI), which is a reaction product of carboxy-PTIO and NO, showed that conversion of carboxy-PTIO to carboxy-PTI was augmented by LPS treatment due to the increased production of NO, and that the enhanced conversion (PTIO-->PTI) was significantly inhibited by administration of N omega-monomethyl-L-arginine. This indicates that carboxy-PTIO exhibits a potent therapeutic value in endotoxin shock through the direct scavenging action against NO.

Animals↗