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Biomedical subjects

S Okamoto

Publications and source records attributed to S Okamoto.

At least 235 records · Page 13Linked to original sources

Clinical factors influencing posttransfusion platelet increment in patients undergoing hematopoietic progenitor cell transplantation--a prospective analysis.

BACKGROUND: Platelet transfusion refractoriness remains problematic in the management of patients who have undergone hematopoietic progenitor cell transplantation. Bone marrow transplantation itself is reported to be a relevant factor hampering efficient platelet transfusions. However, a prospective analysis assessing factors affecting platelet transfusion efficacy in the setting of hematopoietic progenitor cell transplantation has yet to be conducted. STUDY DESIGN AND METHODS: To identify factors independently influencing platelet transfusion efficacy after hematopoietic progenitor cell transplantation, a prospective study was performed to determine the effectiveness of platelet transfusions by estimating posttransfusion (16-hour) corrected count increments (CCI) in 42 consecutive patients (26 who received allogeneic transplants and 16 who received autologous transplants) with 439 available platelet transfusions. RESULTS: The mean CCI and percentage of CCI <4500 for all transfusions were 6161.1 +/- 7775.2 per microL and 42.1 percent, respectively. Multiple linear regression analyses revealed high total bilirubin, total body irradiation, high serum tacrolimus, and high serum cyclosporin A to be major factors independently predicting a lower CCI. HLA antibodies with restricted specificity and platelet antibodies were detected transiently in 17 and 14 percent of the patients, respectively. The presence of these antibodies was not, however, associated with a poor response to platelet transfusions. CONCLUSION: Platelet transfusion efficacy in hematopoietic progenitor cell transplant recipients is markedly influenced by clinical factors specific to the procedure as well as those already recognized in other settings. Alloimmunization is not, however, a major factor associated with a poor response to platelet transfusions after this procedure.

Adolescent↗

Role of inflammatory cytokines in induction of anterior chamber-associated immune deviation.

PURPOSE: To determine the extent to which proinflammatory cytokines [(interleukin-I-beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), gamma-interferon (gamma-IFN)] interfere with induction of anterior chamber-associated immune deviation (ACAID). METHODS: Proinflammatory cytokines were injected intracamerally prior to local injection of ovalbumin (OVA), or added to cultures containing peritoneal exudate cells (PEC), transforming growth factor-beta (TGF beta), and OVA. After incubation, these cells were washed and injected intravenously into naive, syngeneic mice. One week later, the mice were immunized with OVA in adjuvant, and delayed hypersensitivity (DH) was assessed seven days later. RESULTS: Eyes pretreated with IL-1 beta, TNF alpha or gamma-IFN failed to support ACAID induction. In addition, IL-1 beta and gamma-IFN robbed OVA-pulsed, TGF beta-treated PEC of their ability to induce ACAID, whether the inflammatory cytokines were added prior to, simultaneously with, or after exposure to TGF beta. By contrast, in-vitro exposure of PEC to TNF alpha was unable to prevent TGF beta-promoted ACAID. CONCLUSION: IL-1 beta, gamma-IFN, and TNF alpha injected intracamerally rob the eye of immune privilege and prevent ACAID induction. In the cases of IL-1 beta and gamma-IFN, ACAID seems to be prevented by a direct action of the cytokines on antigen-presenting cells (APCs). In the case of TNF alpha, prevention of ACAID in vivo probably occurs by an APC-independent mechanism.

Animals↗

Increased plasma levels of substance P and disturbed water excretion in patients with liver cirrhosis.

BACKGROUND: The pathogenesis of impaired water excretion in liver cirrhosis has not been fully elucidated. METHODS: We induced an intravenous water overload of 20 ml/kg body weight in 10 cirrhotics without ascites (CLC), 11 cirrhotics with ascites (DLC), and 10 normal subjects (N) and investigated the relationship of plasma levels of substance P (SP), norepinephrine (NE), and antidiuretic hormone (ADH) to impaired water excretion. RESULTS: Free water clearance (CH2O) was lower in DLC (mean, 2.7 ml/min) than in N (8.3 ml/min; P < 0.001) and CLC (6.9 ml/min; P < 0.001). In DLC the creatinine clearance (CCr), maximal urine flow rate/CCr, (CH2O + CNa)/CCr, and mean arterial pressure (MAP) were significantly lower than in N and CLC. There was a progressive increase in basal SP, from lowest in N to CLC, to highest in DLC. Basal NE increased in CLC and DLC. Basal ADH did not differ among N, CLC, and DLC. In cirrhotics CH2O was correlated positively with serum albumin and cholinesterase and negatively with the retention rate of indocyanine green at 15 min. Basal SP was negatively correlated with CH2O (r= -0.71: P < 0.001) and MAP (r= -0.56; P < 0.005). Basal NE was correlated positively with basal SP (r= 0.67, P < 0.01 ). CONCLUSIONS: Decreased CH2O is closely related to the severity of the liver disturbance. Decreased CCr and reduced delivery of filtrate to the ascending limb of the loop of Henle secondary to an increased sodium reabsorption in the proximal tubule may play an important role in the impairment of water excretion. The increase in SP, which has a potent vasodilatory action, and the associated enhanced activity of the sympathetic nervous system may be responsible for the mild or moderate impairment of water excretion in the absence of nonosmotic hypersecretion of ADH in cirrhotics with ascites.

Adult↗

Cationic liposome-mediated efficient induction of type I interferons by a low dose of poly I:poly C in mouse cell lines.

Double-stranded polyriboinosinic acid:polyribocytidylic acid (poly I:poly C) is a powerful inducer of type I interferons (IFNs). However, the dose of poly I:poly C required for efficient IFN induction is so high as occasionally to be cytotoxic. In this work, we examined the IFN-inducibility of poly I:poly C complexed with several cationic reagents in mouse fibroblast L cells and found that Lipofectin and LipofectACE can induce the production of a substantial amount of type I IFNs (mostly beta-type) even at a two-order lower dose compared with poly I:poly C alone. Such effects of poly I:poly C were optimal at 0.1 microgram/ml for 2-10 microgram/ml of Lipofectin and LipofectACE. These conditions caused no significant cytotoxicity in the recipient cells. Furthermore, a short treatment (less than 10 min) with the complexes was sufficient for the maximum induction. This IFN induction method was applicable to other cell types and other species including human. Hence, our observations may pave the way for clinical application of the IFN inducer.

Animals↗

Acquisition of certain streptomycin-resistant (str) mutations enhances antibiotic production in bacteria.

Physiological differentiation (including antibiotic production) in microorganisms usually starts when cells encounter adverse environmental conditions and is frequently accompanied by an increase in the accumulation of intracellular ppGpp. We have found that the acquisition of certain streptomycin-resistant (str) mutations enables cells to overproduce antibiotics, demonstrating an increase in productivity 5- to 50-fold greater than that of wild-type strains. The frequency of such antibiotic-overproducing strains among the str mutants was shown to range from 3 to 46%, as examined with several strains of the genera Streptomyces, Bacillus, and Pseudomonas. Analysis of str mutants from Bacillus subtilis Marburg 168 revealed that a point mutation occurred within the rpsL gene, which encodes the ribosomal protein S12, changing Lys-56 (corresponding to Lys-43 in Escherichia coli) to Asn, Arg, Thr, or Gln. Antibiotic productivity increased in a hierarchical manner depending upon which amino acid residue replaced Lys at this position. The strA1 mutation, a genetic marker frequently used for mapping, had no effect on antibiotic productivity even though it was found to result in an amino acid alteration of Lys-56 to Ile. Gene replacement experiments with the str alleles demonstrated unambiguously that the str mutation is responsible for the antibiotic overproductivity observed. These results offer a rational approach for improving the production of antibiotic (secondary metabolism) from microorganisms.

Alleles↗

Application of a novel method for subsequent evaluation of sinusoids and postsinusoidal venules after ischemia-reperfusion injury of rat liver.

Although several intravital fluorescence microscopic studies demonstrated that microcirculatory derangement is induced during liver ischemia-reperfusion, these data were obtained from randomly selected microvascular areas and microvessels. Repeated observation of the identical microvessels has not been performed yet. Using a specially designed cover glass, it is now possible to relocate desired sites of observation repeatedly over the whole reperfusion time. The aim of this study was to determine the impact of reperfusion time on hepatic microvascular perfusion state. Twenty minutes of ischemia induced a significant decrease in sinusoidal perfusion rate (29.1 +/- 10.2%) as compared with baseline values (98.0 +/- 0.3%). At 30, 60, and 120 min of reperfusion, the percentage of perfused sinusoids recovered to 62.8 +/- 6.6, 67.5 +/- 5.7, and 77.2 +/- 5.4%. The number of stagnant leukocytes in the same sinusoids was 6.2 +/- 1.9/lobule at baseline and increased to 22.3 3.6/lobule at 120 min of reperfusion. The number of leukocytes adhering within postsinusoidal venules was 53.5 12.5/mm2 before ischemia and increased to 414.2 62.5/mm2 at 120 min of reperfusion. We have demonstrated that during 120 min of reperfusion, there was a steady increase in both sinusoidal and venular leukocyte adhesion along with an attenuation of the initially severely depressed sinusoidal perfusion. A no-reflow phenomenon at an early phase of reperfusion and subsequent reflow were proven.

Animals↗

Abdominal aortic thrombosis in a patient with nephrotic syndrome.

We report a patient who presented with severe nephrotic syndrome complicated with infrarenal aortic and right renal arterial thrombosis. The nephrotic syndrome frequently causes thromboembolic complications in veins, but arterial thrombosis is relatively rare, especially in the aorta. Various predisposing factors leading to thromboembolic complications are discussed. In this case, the thromboembolic complication may have some clinical association with the hypercoagulable state in nephrotic syndrome.

Aorta, Abdominal↗

Identification, genomic organization, and alternative splicing of KNSL3, a novel human gene encoding a kinesin-like protein.

Proteins of the kinesin superfamily are microtubule-dependent molecular motors that play important roles in organelle transport and cell division. Through genomic sequencing and use of the RT-PCR technique, we have identified and characterized KNSL3 (kinesin-like 3), a novel member of the kinesin-like protein family in humans. We determined its genomic organization and detected four alternatively spliced transcripts. KNSL3 was expressed ubiquitously, but sizes and relative amounts of the major products were different in each of the tissues examined. Alternative splicing, along with the multiplicity of genes in the molecular family that includes KNSL3, produce diversity among the C-terminal ends of kinesins. These observations may contribute to an understanding of the specificity of different kinesins with respect to organelle binding.

Alternative Splicing↗

Purification method for human plasma kallikrein by a new affinity chromatography.

We synthesized a new affinity gel (PKSI-Toyopearl) using a selective synthetic inhibitor of plasma kallikrein (PKSI-527) as an affinity ligand, and employed it for the rapid purification of plasma kallikrein from human plasma. Human plasma activated with kaolin after acid treatment was applied to a PKSI-Toyopearl column. Adsorbed protein was eluted with 50 mM glycine-hydrochloric acid buffer (pH 3.0). Plasma kallikrein was purified 181-fold with a yield of 85% from the kaolin-activated plasma. Further purification was performed by chromatography on a DEAE-Toyopearl 650M column. Plasma kallikrein was finally purified 1720-fold with a 63% yield by these procedures. On sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, a band was observed at approximately 88 kDa. These findings indicate that PKSI-Toyopearl is a valuable tool for the purification of plasma kallikrein from human plasma.

Blood↗

Design of plasma kallikrein inhibitors: functional and structural requirements of plasma kallikrein inhibitors.

The synthetic plasma kallikrein (PK) inhibitor trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyme thylanilide (PKSI-527) consists of three parts. Each part was replaced by analogues in an attempt to improve the potency and the selectivity of PKSI-527. Among the peptides examined, trans-4-aminomethylcyclohexanecarbonylphenylalanine-4-carboxyan ilide (peptide 16) inhibited PK with a high selectivity and an IC50 value of 2.7 microM, being as potent as PKSI-527.

Drug Design↗

[Flow cytometric DNA analysis and MR imaging of salivary gland tumors].

We correlated the histopathology of 32 cases of salivary gland tumors with MR imaging and flow cytometric DNA analysis. All malignant tumors were invasive and/or had an ill-defined margin. Fifty-seven percent of the pleomorphic adenomas were shown as a high signal intensity area on T2 weighted images. Fifty-six percent of Warthin tumors were shown as a low or iso signal intensity area on T2 weighted images associated with the cystic portion. Sixty-seven percent of malignant tumors were characterized by DNA aneuploidy and/or a total percentage of the S-phase fraction plus the G2 + M fraction higher than 10%. It was less than 10% and the Ki-67 positive fraction was higher than 20% in all pleomorphic adenomas. The Ki-67 positive fraction was less than 20% in 78% of Warthin tumors. The histopathology of all malignant tumors, 86% of the pleomorphic adenomas, and 89% of Warthin tumors was correctly predicted by the combination of MR images and flow cytometry. We suggest that the MR images combined with flow cytometric analysis of fine needle aspiration-derived materials is useful in the pre-operative histopathologic diagnosis of salivary gland tumors.

Adenolymphoma↗

Spontaneous regression of malignant lymphoma of the stomach.

We report a case of complete and spontaneous regression of malignant lymphoma of the stomach. A submucosal tumor with central ulceration was detected on the greater curvature of the stomach in a 63-year-old woman. The tumor was diagnosed histopathologically as a diffuse large B-cell lymphoma (REAL classification). The tumor disappeared 18 days later without chemotherapy. Examination at that stage showed Helicobacter pylori (H. pylori), which was later treated with antibiotics. There was no evidence of recurrence of the malignant lymphoma at the last follow-up conducted at the time of preparation of this report, 13 months after the initial diagnosis. Spontaneous regression of an intermediate and high-grade non-Hodgkin's lymphoma is uncommon. We discuss the possible role of H. pylori in the regression of gastric malignant lymphomas.

Biopsy↗

[The mechanism of corneal epithelial disorder induced by prostaglandin F2 alpha isopropyl unoprostone].

Deleterious effects of isopropyl unoprostone (PG-F2 alpha) on the ocular surface were evaluated using the in vivo barrier function assay of corneal epithelial cells and the proliferation assay of human corneal epithelial cells in vitro. The barrier function of corneal epithelial cells in vivo was not impaired by treatment with PGF2 alpha, but it was significantly suppressed by timolol. The result of cell proliferation assay of human corneal cells showed that the 0.12% PGF2 alpha ophthalmic solution caused greater suppression of cell proliferation and acuter cell toxicity than 0.5% timolol ophthalmic solution. Further study showed that not the vehicle but the PGF2 alpha itself was responsible for these deleterious effects. We conclude that the 0.12% PGF2 alpha ophthalmic solution affects cell migration and proliferation but not the barrier effects of the ocular surface. These results suggest that the corneal epithelial defect of glaucoma patients may be caused by these two independent mechanisms, namely suppression of cell proliferation by PGF2 alpha and the destruction of the barrier function of the ocular surface by timolol.

Adrenergic beta-Antagonists↗

[Severe hepatic veno-occlusive disease (VOD) which was successfully treated with supportive therapy, but subsequently developed late-recurrence].

A 40-year-old man with chronic myelogenous leukemia in chronic phase received an allogeneic marrow graft from his HLA identical brother. He was conditioned with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). Graft-versus-host disease (GVHD) prophylaxis was attempted with cyclosporine A (CYA) and methotrexate. On day 30, weight gain, ascites and hepatomegaly developed in addition to an elevation of total bilirubin (TB). He was diagnosed as having veno-occlusive disease (VOD) and treated conservatively. The TB level increased up to 20.1 mg/dl on day 66, then reduced to 2.1 mg/dl on day 129. By that time ascites and hepatomegaly also had completely resolved. However, on day 134. The TB level started to increase again, when the lesions of chronic GVHD were observed in the eye, the mouth, and the skin. CYA was started on day 142, and FK506 was substituted for CYA on day 161. Despite the improvement of oral and skin lesions, TB level continued to rise, and he died of respiratory failure due to ARDS on day 186. Autopsy revealed both acute and old hepatic VOD lesions, suggesting the occurrence of late-onset VOD which probably contributed to the liver dysfunction observed after clinical resolution of the first episode of VOD.

Adult↗

Dermatofibrosarcoma protuberans and its fibrosarcomatous variant with areas of myoid differentiation: a report of three cases.

AIMS: We describe three examples of dermatofibrosarcoma protuberans which demonstrated focal myofibroblastic differentiation, and discuss the nature of myofibroblastic differentiation. METHODS AND RESULTS: We studied three cases of dermatofibrosarcoma protuberans, two of which had fibrosarcomatous portions containing myoid areas, and one which showed myoid areas in ordinary dermatofibrosarcoma protuberans. Myoid areas were recognized histologically as randomly distributed, scattered bundles or small nodules of spindle cells with deeply eosinophilic cytoplasm. Myofibroblastic differentiation was demonstrated immunohistochemically by positive staining for smooth muscle actin and muscle-specific actin, and ultrastructurally by the presence of microfilament bundles with focal dense bodies and pinocytic vesicles. The myoid areas occasionally contained intraneoplastic blood vessels. CONCLUSION: The presence of myoid areas may be related to reactive hyperplasia of stroma, and its relation to the histogenesis of dermatofibrosarcoma protuberans is uncertain.

Actins↗

[Experience of coronary and great vessel angiography by transradial puncture].

The introduction of 5F and even 4F catheters allows transradial coronary arteriography and aortography. The efficacy and limitation of angiography via the radial artery using 5F catheter was prospectively evaluated in 200 consecutive patients. Cardiac catheterization with diagnostic angiography was successfully performed in 198 of 200 patients, including 11 patients with acetylcholine provocation test, 21 with bypass graft angiography, 38 with aortography and 5 with biopsy of the left ventricular myocardium. The transradial approach was not indicated in one patient without normal Allen's test and in one with weak radial pulse. In four patients, guide wire support was needed during manipulation because of marked tortuosity in the innominate artery. The sheath was removed immediately after the completion of the procedure, followed by 5 hours of tourniquet hemostasis without manual compression. The postoperative resting period was reduced. Peripheral vasospasm occurred in 2.5% of cases, but could be eliminated by administration of isosorbide dinitrate and lidocaine. Subcutaneous hemorrhage in the puncture site was observed in 3.0% of cases, but required no additional compression. Transradial catheterization is a minimally invasive, safe and practical alternative to the brachial or femoral artery approach in patients with normal Allen's test.

Aortography↗

[A case of renal oncocytoma associated with acquired cystic disease of the kidney].

We report a case of renal oncocytoma associated with acquired cystic disease of kidney (ACDK). A right renal mass was incidentally found on an annual ultrasonography of the kidneys in a 56-year-old female patient who had been on maintenance hemodialysis for 6 years. Computerized tomography (CT) showed a right hypervascular renal mass, suggesting a renal cell carcinoma associated with ACDK. Right radical nephrectomy was performed. The post-operative pathological diagnosis was renal oncocytoma. Renal oncocytoma in ACDK is very rare, and the pathological characteristics of oncocytoma are discussed.

Adenoma, Oxyphilic↗

[Evaluation of the FREEDOM O2, DC Concentrator, a portable oxygen concentrator capable of operating under car battery power].

UNLABELLED: The FREEDOM O2 DC Concentrator, an oxygen concentrator which can be powered by a car battery, was evaluated. The oxygen concentrator was used by a 67 year-old man with sequelae of pulmonary tuberculosis who was receiving long-term oxygen therapy at home (HOT), and whose work required automobile trips over long distances. The equipment used was an adsorption-type oxygen concentrator capable of operating on a DC 12 V power supply, and which can be powered from a residential power outlet (AC 100 V) using a dedicated voltage converter. The trunk-shaped equipment measured 21/584 x 42 cm and weighed 17 kg. The noise level of the equipment was 58.2 +/- 2.5 dB (at 1 meter), and the flow rate can be set to 0.25, 0.50, 0.75, 1.0, 1.5, and 2.0 l/min. RESULTS: 1) The O2 concentration which can be generated by this equipment is 93 +/- 3% (0.25 to 1.5 l/min) or 90 +/- 2.8% (2.0 l/min). 2) Using this equipment, the patient was capable of driving himself in comfort for two hours or longer. Further, it was possible to stay in a hotel during a trip, inhaling oxygen generated by the equipment. Hereafter, this equipment should enable or facilitate long-distance driving, travel and lodging for HOT patients.

Aged↗