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Biomedical subjects

Y Okada

Publications and source records attributed to Y Okada.

At least 667 records · Page 37Linked to original sources

[Size estimation method for patch used in reconstruction of LV cavity].

The reconstruction of LV cavity is accomplished by suturing a patch to the viable myocardium to exclude the infarcted area from the high LV pressures. However, there is no clear guideline to estimate the size of patch used for LV reconstruction. We have designed a new method to determine the correct patch size, and applied it in 5 cases. The suture line of the patch is at the junction of contractile (functional) and infarcted portions of LV. The patch size is determined by the length of AB, termed "a", as the base, where "point A" represents the junction on the LV anterior wall side, and "point B" the junction of the LV posterior wall side, from RAO 30 degrees projection of the left ventriculogram obtained by cardiac catheterization. In LV aneurysm, we designed the patch in the range of a/2 < l < or = pi a/2, where patch length on RAO 30 degrees is considered "l". An effort was made to reconstruct to normalize LV volume and contour by designing the patch size to be a/2 < l < a, particularly when the contractile portion was enlarged by aneurysm. On the other hand, in post AMI VSD, LV contractile portion is not enlarged in early stage. Therefore, the patch was designed in the range of a < l < or = pi a/2 to maintain LV volume. Postoperative LV volume can be calculated prior to surgery, by using the lengths of the designed patch. Postoperative analysis indicated that the actual LV volume and contour were almost identical to our estimation. This method is very useful in planning the patch size for LV reconstruction.

Aged↗

Effects of plasma kallikrein specific inhibitor and active-site blocked factor VIIa on the pulmonary vascular injury induced by endotoxin in rats.

The acute respiratory distress syndrome (ARDS) is a serious complication of sepsis. To evaluate the role of the coagulation system in the pathogenesis of ARDS in sepsis, we examined the effects of the administration of a synthetic plasma kallikrein specific inhibitor (PKSI) and of active-site blocked factor VIIa (DEGR-VIIa) on the pulmonary vascular injury induced by E. coli endotoxin (ET) in rats. Administration of PKSI prevented the pulmonary vascular injury induced by ET as well as pulmonary histological changes in animals administered ET, but it did not affect the intravascular coagulation. The opposite effect was seen with DEGR-VIIa, which prevented the intravascular coagulation but not the pulmonary vascular injury. PKSI did not inhibit the activation of the complement system induced by ET leading to the activation of neutrophils. Findings suggest that PKSI may prevent the pulmonary vascular injury induced by ET by inhibiting kallikrein, which activates the neutrophils. The intrinsic pathway of coagulation may be more important than the extrinsic pathway in the pulmonary vascular injury produced by ET.

Amino Acid Chloromethyl Ketones↗

[Investigation of doxorubicin cardiotoxicity by echocardiogram and the appropriate method of using doxorubicin].

For a sample of 136 adults on whom Doxorubicin (DXR) had been used, we looked for the ejection fraction (EF) by echocardiography and examined its relationship with the amount of DXR. Our results showed that as the amount of DXR increased the EF decreased significantly, particularly with aging. The use of previous mediastinal radiation and 5-FU, etc. on breast cancer patients had no effect on the EF. From our examination of patients developing congestive heart failure, we repeatedly performed echocardiography and found that DXR can be safely used until the EF decreases to 55 percent. In this way, we can find many patients with whom it is possible to use DXR in larger amounts than 550 mg/m2. In general, large quantities of DXR can be used on young people, but for elderly people, large quantities of DXR should be used with caution.

Adult↗

Serum amyloid P component enhances induction of murine amyloidosis.

Serum amyloid P component (SAP), a common component of all known types of amyloid fibrils, protects amyloid fibrils from proteolysis in vitro. It is therefore speculated to contribute to the deposition of amyloid fibrils in various types of amyloidoses. However, a role for SAP in amyloid deposition is not yet known. To investigate the relationship between SAP and amyloid deposition, we used gene targeting techniques to generate a unique strain of mice carrying a null mutation at the sap locus. The resultant SAP-deficient mice displayed no obvious phenotypic abnormalities. We asked whether experimental amyloid A (AA) amyloidosis could be induced in the SAP-deficient mice. The wild-type and SAP-deficient mice did not differ in their synthesis of serum amyloid A, the precursor protein of AA amyloid fibril, in response to acute inflammation. The induction of AA amyloidosis, however, was significantly retarded in the SAP-deficient mice relative to wild-type mice. Our experiments present, for the first time, compelling evidence that, although not essential in the deposition of AA amyloid, SAP significantly accelerates this reaction. Thus, SAP enhances the induction of murine amyloidosis and may play an important role in the pathogenesis of human amyloidoses, including Alzheimer's disease.

Acute-Phase Reaction↗

[Small cell carcinoma of the urinary bladder: a case report and review of the Japanese literature].

A 50-year-old man presented with asymptomatic gross hematuria which he had first noticed 3 months earlier. Clinical examinations revealed a non-papillary, broad-based tumor on the left lateral wall of the urinary bladder with a clinical stage of T3N0M0. The pathological diagnosis of a transurethral biopsy tissue specimen was small cell carcinoma. Neoadjuvant intraarterial infusion chemotherapy using cisplatin and adriamycin was initially administered but proved to be ineffective. Thus, we performed a radical cystectomy. The tumor tissue was apparently homogenous and composed of small cells arranged in sheets and solid patterns, and was staged to be pT3bR1L2V0N0. An electron microscopic study confirmed small cell carcinoma with neurosecretory granules. Postoperatively, 4 courses of adjuvant chemotherapy consisting of cisplatin, etoposide and ifosfamide were administered. The patient is alive without any evidence of tumor recurrence 26 months after the operation.

Antineoplastic Combined Chemotherapy Protocols↗

[Anesthesia in two patients with essential thrombocythemia].

Case 1. The patient was a 69-year-old man with essential thrombocythemia (ET), who underwent urgent laparotomy. On admission he was dehydrated and the platelet count was more than 160 x 10(4).microliter-1, with hematocrit of 50%. Anesthesia was induced with ketamine i.v. and maintained with nitrous oxide and sevoflurane in oxygen. Postoperative care included the administration of gabexate mesilate (GM) which is an antiplatelet agent. Case 2. An 84-year-old woman with ET was diagnosed as gastric cancer and elective gastrectomy was scheduled. The platelet count was more than 100 x 10(4).microliter-1. The patient was anesthetized with nitrous oxide and oxygen supplemented with fentanyl and mepivacaine via epidural catheter. Intravenous infusion of GM was performed at a rate of 1 mg.kg-1.hr-1 during surgery. PF-4 and beta-TG were measured. These are platelet releasing factors. The level of PF-4 decreased to normal level during this procedure. In conclusions, it will be important to use GM during anesthesia in order to avoid the complications such as myocardial or pulmonary infarction caused by thrombocythemia.

Aged↗

[A case of traumatic hematoma in the basal ganglia: successful drainage with ultrasound-guided aspiration surgery via burr hole].

A case was reported of massive traumatic hematoma of the basal ganglia which was treated successfully by ultrasound-guided aspiration surgery. A 8-year-old girl was transferred to our hospital 20 minutes after a traffic accident. She was in stupor and had right hemiplegia. A skull x-rays showed right temporal linear fracture and a head CT disclosed left massive putaminal hematoma. Ultrasound-guided aspiration surgery via a burr hole was performed under general anesthesia and 30 ml of hematoma was successfully evacuated. Her symptoms and signs improved gradually and she was discharged on foot 3 weeks after the accident. The clinical feature and mechanism of development of the hematoma in this lesion, and usefulness of ultrasound-guided aspiration surgery were also discussed.

Basal Ganglia↗

Non-enzymatic hydrolyses of aryl esters of thymidine 3'-monophosphate as probes for the rate-determining step in DNA hydrolysis.

In order to shed light on the rate-limiting step in DNA hydrolysis, non-enzymatic hydrolyses of aryl esters of thymidine 3'-monophosphate have been kinetically examined. In alkaline solutions, these dinucleotide analogues were hydrolyzed far faster than was thymidylyl(3'-5')thymidine (TpT), indicating that the departure of the leaving group from the phosphorus atom is rate-limiting. The CeIV- and CeIV/PrIII combination-mediated hydrolyses of these analogues were also faster than the corresponding hydrolysis of the dinucleotide.

Cerium↗

Non-selective cation conductance in a Xenopus renal epithelial line.

The currents activated in single cells of an epithelial cell line from renal tubules of Xenopus laevis, were studied, using a whole-cell voltage-clamp technique. After the patched membrane was broken for the whole-cell recording, the currents developed transiently, reaching a peak in 20 min, in cells held under voltage-clamp. The currents did not show voltage- and time-dependent gating behavior at membrane potentials between -100 and +100 mV. The current-voltage relationships showed strong outward rectification. The ratio of the absolute amplitude of the current at a potential of +60 mV to that at -60 mV was 24.4 +/- 3.6. The reversal potentials of the currents under various ionic conditions imply that the membrane conductance was preferentially permeable to cations but that it had a finite permeability to anions. The cation conductance was non-selective for monovalent cations and also permeable to Ca2+, with a permeability sequence (relative to Na+); Na+: K+: Cs+: Li+: Ca2+ = 1.0: 1.3: 1.4: 1.0: 0.7. These results suggest that in A6 cells, the non-selective cation conductance activated after the rupture of the patch membrane, may play an important role in epithelial transport of fluid and electrolyte and that its Ca2+ permeability could be involved in some physiological signal transduction.

Animals↗

Mapping of host range restriction of the rakkyo strain of tobacco mosaic virus in Nicotiana tabacum cv. bright yellow.

The rakkyo strain (TMV-R) and the common strain (TMV-U1) of tobacco mosaic virus exhibit distinct host range differences. TMV-R infects rakkyo plants, a monocot host that TMV-U1 is unable to infect. However, TMV-R causes only latent infection in Nicotiana tabacum cv. Bright Yellow (BY) in inoculated leaves, whereas TMV-U1 infects BY systemically and induces mosaic symptoms. Complete nucleotide sequencing of the TMV-R genomic RNA revealed amino acid changes in the 130K/ 180K replicase proteins, the 30K protein, and the coat protein and nucleotide changes in the 5' and 3' noncoding regions compared to TMV-U1. To identify viral components involved in determination of differences in host range, we have mapped determinants for the differential infection phenotype in BY plants by constructing chimeric viruses between the two strains in the present study. Examination of the infection phenotypes of the 14 constructed chimeric viruses in BY showed that determinants defining the differential infection phenotype in BY reside in the 130K/180K replicase proteins and the 3' noncoding region. Cognate combination of the 130K/180K replicase proteins and the 3' noncoding region of TMV-U1 origin is required to produce systemic infection in BY plants.

DNA-Directed DNA Polymerase↗

Expression of membrane-type matrix metalloproteinase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay.

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a member of the recently identified unique membrane-type subgroup in the matrix metalloproteinase (MMP) family. MT1-MMP has proteolytic activity against components in the extracellular matrix and activates progelatinase A (72-kDa type IV procollagenase/proMMP-2) on the cell surface. Because MT1-MMP is frequently expressed in a variety of tumors, we examined its contribution to their metastatic potential. The mouse lung carcinoma cell line Madison 109 was transiently transfected with a MT1-MMP expression plasmid and inoculated into the tail vein of BALB/c mouse. Fate of the transfected cells was monitored by the neo(r) gene in the plasmid using the quantitative PCR method. The survival rate of the parental cells in lung was 0.7% of the inoculated cells. It was increased by 3-fold with the MT1-MMP transfected cells and the number of the lung nodules increased accordingly. Immunostaining of the consecutive tissue sections revealed that lung nodules expressing MT1-MMP were positive for gelatinase A as well, whereas MT1-MMP-negative cells were not stained for gelatinase A at all. Thus, MT1-MMP-expressing cells acquire specific ability to bind exogenous progelatinase A.

Animals↗

Intracellular glutathione as a possible direct blocker of HIV type 1 reverse transcription.

In AIDS patients, chronic inflammation and elevated levels of cytokines seem to be associated with reduced levels of glutathione (GSH). GSH has been proposed to inhibit the activation of NF-kB, which results in the inhibition of HIV-1 replication. Here, we show the evidence that GSH and N-acetylcysteine, but not L-cysteine or dithiothreitol, could inhibit the reverse transcriptase (RT) process of HIV-1. Such inhibition was not observed with the RT of murine leukemia virus.

Acetylcysteine↗

Hypocalcemia associated with 5-fluorouracil and low dose leucovorin in patients with advanced colorectal or gastric carcinomas.

BACKGROUND: The biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) has demonstrated significantly increased response rates in comparison with the use of 5-FU alone in patients with advanced colorectal carcinoma. However, the higher response rate of LV/5-FU may occur at the expense of increased toxicity and side effects such as diarrhea, myelosuppression, and mucositis. During chemotherapy, a high incidence of hypocalcemia associated with this chemotherapy regimen was noted. This study was therefore aimed at assessing the side effects of chemotherapy using low dose LV/5-FU on calcium metabolism. METHODS: Twenty-five patients with advanced gastric or colorectal carcinoma were treated with chemotherapy comprised of low dose LV administered at 20 mg/m2/ day by intravenous bolus, followed by 1-hour intravenous infusion of 5-FU at 425-600 mg/m2/day for 5 consecutive days every 28 days. RESULTS: The toxic effects were generally mild, and included diarrhea, mucositis, leukopenia, and nausea/vomiting. Fifteen patients (65%) experienced hypocalcemia. The plasma 1,25-(OH)2D3 levels were significantly reduced on Day 5 due to the chemotherapy. CONCLUSIONS: The toxic effects of the regimen were generally mild. However, a high percentage of hypocalcemia occurred with the combination of LV/5-FU. It is therefore necessary to examine carefully the serum calcium levels of patients when using this chemotherapeutic modality.

Aged↗

External-anion-dependent anionic current in blastoderm cells of early medaka fish embryos.

1. Anionic current was studied by a whole-cell variation of the patch-clamp technique in blastoderm cells dissociated from medaka (Oryzias latipes) embryos at the early blastula stage. The blastoderm cells were mechanically dissociated without using proteolytic enzymes. 2. The anionic current was deactivated by hyperpolarizing steps. The steady-state current-voltage (I-V) relationship of the anion current was accurately represented by the Boltzmann relation with z = 1.01 +/- 0.02 (+/- S.E.M., n = 4) for voltage-dependent activation when internal calcium ions were buffered at 100 nM by BAPTA-Ca2+ buffer. 3. When the internal calcium concentration was reduced to 10 nM, this anionic current became an external-calcium-dependent current and was remarkably decreased by removal of external calcium ions. Furthermore, this anionic current was almost abolished when the internal calcium concentration was greatly reduced by chelating Ca2+ ions with 10 mM BAPTA. 4. This current was not affected by replacing external Na+ with TEA+ or N-methyl-D-glucamine. The reversal potentials shifted by +58.6 mV for a 10-fold decrease in the external Cl-concentration. External Cl-ions were substituted with various anions and respective current-reversal potentials were measured. The order of permeability was I- > Br- > Cl- > F-. Both the outward and inward currents almost disappeared in external Cl(-)-free solutions. 5. The voltage dependency of the anionic current shifted in a positive direction with the reduction in the external Cl- concentration, the potentials at which half the channels were activated (V 1/2) being -59.8 +/- 1.2 mV (n = 4), -40.7 +/- 0.8 mV (n = 4), -14.9 +/- 0.7 mV (n = 4), and -0.7 +/- 0.6 mV (n = 4) for 135, 90, 67, and 45 mM Cl-, respectively. This implies that the inward current, brought by efflux of internal anions, decreases with reductions in the external Cl- concentration. In the presence of external 135 mM Br-, the voltage dependency of the anionic current shifted in the negative direction (V 1/2 = -84.5 +/- 1.0 mV and z = 0.91 +/- 0.02 (n = 3)) in comparison with that in the external Cl- medium. It further shifted in the negative direction in the presence of 135 mM I- (V 1/2 = -93.8 +/- 1.5 mV and z = 0.85 +/- 0.03 (n = 3)). The inward current of the anion channel is considered to be affected by both the type and the concentration of external halide ions. 6. At the beginning of the blastula stage, the blastocoel cavity is formed for the first time. A mechanism is necessary to transport ions to the cavity without losing them to pond water outside the embryos. Since this anion channel is external-anion dependent, the current cannot be activated in the membrane facing the pond water, where concentrations of anions are much lower than those of the intracavernous solution. Only after blastocoel formation are blastoderm cells first exposed to the extracellular fluid with high ionic concentrations. Then, the anion channel would become effective for maintaining the Cl- equilibrium potential.

Animals↗

Relaxed specificity of matrix metalloproteinases (MMPS) and TIMP insensitivity of tumor necrosis factor-alpha (TNF-alpha) production suggest the major TNF-alpha converting enzyme is not an MMP.

Tumor necrosis factor-alpha is released from cells by a proteolytic cleavage. Previous work suggested that a specific, non-matrix metalloproteinase carries out this cleavage, but matrix metalloproteinases have also been implicated. In this paper, we report that none of the matrix metalloproteinases tested cleaved peptide substrates as specifically as the non-matrix metalloproteinase. A matrix metalloproteinase did process tumor necrosis factor-alpha extracted from COS cells, but neither tissue inhibitor of metalloproteinases-1 nor -2 blocked tumor necrosis factor-alpha processing by human monocytes. Moreover, tissue inhibitor of metalloproteinases-1 had at most a partial effect on the in vivo release of the cytokine in mice. We conclude that a non-matrix metalloproteinase is the major physiological tumor necrosis factor-alpha convertase.

ADAM Proteins↗