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Biomedical subjects

T Uchida

Publications and source records attributed to T Uchida.

At least 559 records · Page 31Linked to original sources

Thimerosal induces toxic reaction in non-sensitized animals.

The effects of injection of thimerosal solution on nonsensitized animals was investigated. Intrafootpad injection of thimerosal solution in nonsensitized mice resulted in a swelling response which peaked 1 h after injection and lasted for more than 24 h. Histopathological examination showed that there were severe edema and infiltration of polymorphonuclear neutrophils at the site of injection. An increased vascular permeability was observed after cutaneous injection of thimerosal solution on the back of nonsensitized rats. Since mercuric chloride and methyl mercury induced severer reactions, and thiosalicylic acid had no effect, mercury contained in thimerosal would have caused the reactions observed in this study. These results suggest that part of these hypersensitivity reactions against thimerosal observed among patients were possibly induced by the toxic effect of thimerosal. Therefore, thimerosal contained as a preservative in vaccine may augment the side-effects of the vaccination.

Animals↗

IgE-specific unresponsiveness in mice induced by ovalbumin coupled with murine red blood cells.

Ovalbumin (OVA) was coupled with murine red blood cells (MRBC) using glutaraldehyde. OVA-MRBC conjugate induced anti-OVA IgG antibody production in mice at almost the same level as OVA in alum. However, no IgE antibody production specific for OVA was observed in OVA-MRBC-injected mice. IgE-specific unresponsiveness was also observed in mice injected with OVA coupled with sheep red blood cells (OVA-SRBC), suggesting that our present observation was not restricted to the property of MRBC. These results show the potential ability of antigen-RBC conjugate for the development of vaccine that induces sufficient IgG antibody production without IgE synthesis.

Alum Compounds↗

Emphysematous pyelonephritis, ureteritis, and cystitis in a diabetic patient.

This paper presents a case of gas-forming infection of the urinary tract in a diabetic patient. Plain film and computed tomography scans of the abdomen greatly facilitated clarification of the entire inflammatory process. The patient was cured by early nephrectomy conducted following unsuccessful treatment by percutaneous drainage.

Cystitis↗

A case of posttherapeutic sclerotic change of bone metastasis from renal cell carcinoma which proved histopathologically to be complete response.

A 60-year-old man with renal cell carcinoma and metastases to the right 7th rib and L2 vertebra (T2N0M1, OSS) was treated with interferon-alpha and the uracil and tegafur combination following nephrectomy. One and a half years later on bone scintigraphy, the abnormal accumulation had disappeared at the L2 vertebra and weakened in its intensity at the right 7th rib. Plain X-ray revealed that the metastatic lesion at the right 7th rib had decreased in size and had been replaced by calcification. The right 7th rib was removed surgically and step-sectioned pathological specimens revealed necrosis with no viable cancer cells.

Antineoplastic Combined Chemotherapy Protocols↗

Correlation of ultrasound-measured common carotid artery stiffness with pathological findings.

To quantitatively and noninvasively evaluate common carotid atherosclerosis in a series of patients, we measured the stiffness parameter beta, which represents the mechanical properties of the vessel. beta was calculated from the relationship between blood pressure and the diameter of the artery as measured by an ultrasonic, phase-locked, echotracking system. Increases in the severity grade of atherosclerosis as subsequently determined at autopsy were correlated with increased beta values in 60 common carotid arteries (r = .68). Patients with beta values greater than 13 had a pathological diagnosis of atherosclerosis in the common carotid artery. The sensitivity of this discrimination ratio was 80%, and the specificity was 80% as well. Thus, beta shows promise as a useful diagnostic indicator for detecting asymptomatic common carotid atherosclerosis.

Adult↗

Hypertonic saline dextran prime reduces increased intracranial pressure during cardiopulmonary bypass in pigs.

Children and adults who develop neurologic deficits after cardiac surgery may experience cerebral ischemia during cardiopulmonary bypass. Increased intracranial pressure (ICP) may contribute to cerebral ischemia during bypass. Hypertonic saline dextran (HSD), a hyperosmotic, hyperoncotic resuscitation solution, decreases ICP in trauma resuscitation. We hypothesized that HSD would decrease ICP, reduce brain water, and reduce intravascular fluid requirements during bypass. Twelve swine were divided into two bypass groups: Group 1 (ISO = isotonic) received as prime 1 L of lactated Ringer's solution and 500 mL of 6% hydroxyethyl starch. Group 2 (HSD = hypertonic saline/dextran) received as prime 1 L of lactated Ringer's solution, 500 mL of 6% hydroxyethyl starch, and 1 mL/kg of 24% hypertonic saline/25% dextran. Normothermic bypass was instituted at 100 mL.kg-1.min-1. ICP increased significantly during bypass with ISO prime but not with HSD. Brain water in the cerebrum did not differ between groups but was reduced in the cerebellum to 75.9% +/- 1.4%. We conclude that HSD prevented any significant increase in ICP during normothermic bypass, and substantially improved fluid balance during bypass. In cardiac surgery patients in whom maintaining decreased ICP and reducing isotonic fluid administration is important, HSD may be a useful addition to the bypass prime solution.

Animals↗

4-acylaminophenol derivatives as novel lipoxygenase inhibitors: synthesis and inhibitory effect on 5-lipoxygenase and leukotriene B4 production.

Structure-activity relationships in the inhibitory effects of 4-acylaminophenol derivatives on the 5-lipoxygenase (5-LOX) from RBL-1 cells and leukotriene B4 (LTB4) production by guinea pig neutrophils were studied. When the N-acyl group was n-octanoyl or 2-thiophenecarbonyl and the size of the two ortho substituents of phenol was varied, the substituents bulkier than isopropyl, i.e., 2,6-di-tert-butyl and 2,6-dicyclohexyl, substantially weakened the inhibitory activity in both enzymatic and cellular systems. Among the 2,6-dimethyl derivatives with an acyl group of various carbon-chain lengths (C1-13), those with a n-alkyl chain of C5 to C12 showed similarly potent inhibitory activities toward 5-LOX with an IC50 ranging from 0.27 to 0.66 microM; in contrast, maximal inhibitory activities toward LTB4 production were observed in a narrower range of the serial compounds: i.e., those with a n-hexyl, n-heptyl, or n-octyl chain on the carbonyl carbon formed by far the most inhibitory group of the series and the inhibitory activity sharply decreased on either side of the chain length. Nearly all the active compounds also inhibited cyclooxygenase (COX), but the IC50 values for COX inhibition were more than ten times higher than the corresponding IC50 values for 5-LOX inhibition in most cases, indicating that the acylaminophenols are relatively selective 5-LOX inhibitors.

Aminophenols↗

Oral delivery of poly(lactide-co-glycolide) microspheres containing ovalbumin as vaccine formulation: particle size study.

The objective of the present study was to produce ovalbumin (OVA) loaded poly(lactide-co-glycolide) (PLGA) microspheres with different diameters and to evaluate their possibilities as vaccine formulation in mice following oral inoculation. Four kinds of OVA loaded PLGA microspheres with different mean average volume diameters (1.3, 4.0, 7.5, and 14.0 microns) were manufactured using a w/o/w emulsion/solvent evaporation method. Low loading efficiencies (8-20% w/w) were observed in all batches although smooth spherical particles were obtained. Single oral administrations of OVA loaded PLGA microspheres with different diameters to mice produced immune responses (serum IgG levels by ELISA) which were statistically higher than OVA solution as negative control (Fisher's paired t-test). A dose-response was observed, and single and double inoculation orally produced similar serum antibody levels. The rank of immune response was as follows: 4.0 microns- > 1.3 microns- = 7.5 microns- > 14.0 microns-microspheres. The oral inoculation with 0.13% OVA loaded PLGA microspheres having a mean volume diameter of 4.0 microns exhibited the best immune responses with values greater than those obtained after subcutaneous inoculation with complete Freund's adjuvant (CFA) as positive control, and not significantly different from those obtained after subcutaneous inoculation with the same microspheres.

Adjuvants, Immunologic↗

Relationship between lipophilicity and skin permeability of various drugs from an ethanol/water/lauric acid system.

The in vitro skin permeability of 16 drugs with a wide range of lipophilicity (log P; -0.95-4.40) was evaluated by the use of an ethanol/water (60/40) binary vehicle with or without lauric acid as a permeation enhancer. The enhancing effect by the addition of lauric acid to the ethanol/water (60/40) binary vehicle could be observed from the aspect of both permeation rate and lag time. The permeation rate increased with an increase in the hydrophilicity of the drugs. It was considered that lauric acid exerts an effect on both the polar and nonpolar regions of lipids of the stratum corneum, and the cooperative interaction of ethanol and lauric acid increases the participation of the polar pathway of drugs. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/water (60/40) binary vehicle with lauric acid showed a parabolic shape, with its peak at a more hydrophilic range (log P; 0.19) compared with other past references (log P; 2-3). The ethanol/water (60/40) binary vehicle with lauric acid appears to be a good candidate as a vehicle for transdermal therapeutic systems for hydrophilic drugs.

1-Octanol↗

Detection of 1-acetamino-3-(1-naphthyloxy)-2-propanol as a new metabolite of propranolol.

1-Acetamino-3-(1-naphthyloxy)-2-propanol which is an acetyl conjugate of N-desisopropylpropranolol (AcNDP) was detected as a new metabolite of propranolol (PL) from the incubation medium of isolated rat hepatocyte system and from the urinary extracts of a patient under PL therapy as well as a healthy volunteer given PL. In the case of the hepatocyte systems, the optical selectivity of PL elimination and the metabolite formation were discussed by HPLC determination, and the effect of pretreatment by phenobarbital (PB) or 3-metylcholanthrene (3-MC) on the metabolism was also clarified.

Acetamides↗

Cross reactivity of serum antibodies from chickens immunized with three Eimerian species.

Cross reactivity of serum antibodies from chicken immunized with E. tenella, E. necatrix and E. acervulina was observed. The enzyme linked immunosorbent assay (ELISA) using soluble antigen prepared from oocysts of each species showed the cross reactivity among chicken serum immunized with the three species of protozoa, especially between E. tenella and E. necatrix. In immunoblot analysis with E. tenella oocyst antigen, 7 major bands were detected by homologous E. tenella antiserum and 10 and 6 bands were reacted by E. necatrix and E. acervulina antiserum respectively. In these antigens, the band of 33 kDa was regarded as cross reactive agent between E. tenella and E. necatrix because of high reactivity to both of the antiserum. In addition, the 130 kDa antigen that reacted with every antiserum was regarded as common antigen among these three species.

Animals↗

Disposition and metabolism of a novel diurea inhibitor of acyl CoA: cholesterol acyltransferase (YM17E) in the rat and dog.

1. We have investigated the disposition and metabolism of YM17E after intravenous and oral administration in the rat and dog. 2. Bioavailability of YM17E was 5-9% at oral doses of 3-30 mg/kg in rat, and 9 and 13% at oral doses of 10 and 30 mg/kg in dog. 3. Five N-demethylated metabolites, which have significant pharmacological activity, were found in rat and dog plasma after oral administration. Plasma concentrations of each of these metabolites were comparable with that of unchanged drug. 4. When 14C-YM17E was administered to rat, AUC of unchanged drug was 7% of that of radioactivity. However, AUC of the combined concentration of unchanged drug and five active metabolites was about 50% of that of radioactivity, indicating that the pharmacological activity of the agent was maintained in spite of its biotransformation. 5. After oral administration of 14C-YM17E at a dose of 10 mg/kg to rat, radioactivity was distributed widely to almost all tissues except the brain. The concentration of radioactivity in the liver, one of the target organs, was 65 times higher than that in plasma at 1 h after administration. 6. A significant amount of radioactivity in the liver was located in the microsomal subfraction, which contains much acyl CoA:cholesterol acyl transferase activity. More than 50% of this microsomal radioactivity was derived from unchanged YM17E and five active metabolites. 7. From excretion data in the bile duct-cannulated rat, the absorption ratio of YM17E from the gastrointestinal tract in this species was estimated to be at least 40%, suggesting that the low bioavailability of the drug is due to extensive first-pass metabolism. 8. Some 95% of the administered radioactivity was excreted in the faeces of rat following iv or po doses of 14C-YM17E.

Animals↗

Richter's syndrome showing pronounced lymphadenopathy in response to administration of granulocyte colony-stimulating factor.

A patient with Richter's syndrome developed rapid generalized lymph node enlargement with a decrease of peripheral blood lymphocytes after recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy for neutropenia induced by chemotherapy. The lymphadenopathy subsided spontaneously following discontinuation of rhG-CSF medication. Reinstitution of rhG-CSF therapy was followed by the same response as during initial therapy. Histopathologically, the lesions were characteristic of diffuse large cell lymphoma (DLL) with no evidence of myeloid cell involvement. No spontaneous contraction of enlarged lymph nodes followed withdrawal of the second course, but the enlargement subsided with chemotherapy. The patient died of myocardial infarction. All residual tumors examined post mortem presented microscopic features of small lymphocytic lymphoma (SLL), and G-CSF receptor was demonstrated on these neoplastic cells by Northern blot hybridization analysis. This observation indicates that some B cell malignancies may retain G-CSF receptor and respond to G-CSF.

Aged↗

[Clinical evaluation of measuring system of occlusal force].

An occlusal diagnostic system was evaluated for clinical applications. This system consists of pressure sensitive sheets (DENTAL PRESCALE, Fuji Photo Film Co.) and analyzing computer (OCCLUZER FPD703, Fuji Photo Film Co.). The clinical efficiency of this system was evaluated in aged dentates, aged complete denture wearers and an aged patient suffered from periodontitis. The results were as follows: 1. There was a positive correlation between the masticatory efficiency and maximum occlusal force. 2. In the complete denture wearers, the distances from the medial line to the center of the occlusal load were statistically greater in the adjustment needed cases than in the control group. 3. In a case of periodontitis, the full arch fixed splint was adjusted using this system. After adjustment, the maximum occlusal force and contact area increased, and the maximum and medial pressure of the occlusal contact force decreased. 4. It was suggested that this system would be available for the examination of masticatory efficiency and diagnosis of various types of occlusions.

Aged↗

[Purification and characterization of growth factor extracted from bone].

Local metabolic balance between the bone formation and resorption is modulated by many growth factors present in the bone. The mechanism of this regulation has been investigated by many researchers but is not completely clarified yet. In this study, the author found the presence of several growth factors in the 1 M NaCl extract from the bovine bone and one of them was confirmed to be different from the factors previously reported in the bone tissue. This factor was purified by means of gel filtration and heparin-affinity chromatography and characterized in detail. The purified factor stimulated the proliferation of the fibroblast cell line, Balb/c3T3, but neither stimulated nor inhibited that of the osteoblast cell line, MC3T3-E1. The factor was stable against heat (65 degrees C), acid (2N HCl), 6M urea or 4M guanidine-HCl treatments. However, it was inactivated by trypsin. The molecular size of this factor was about 15,000 and had a high affinity for heparin. In contrast to aFGF or bFGF, the fibroblast-proliferating activity of this factor was suppressed dose-dependently by heparin addition. According to those properties, this factor was indicated to be different from TGF- beta, aFGF, bFGF, PDGF, IGF-I, IGF-II or BMP which were reported to be present in the bone tissue. It is suggested the presence of a new factor in the bone which may regulate the proliferation of fibroblasts in vivo.

Animals↗

[Comparison of tumor markers versus their relative values to prostatic volume in detecting prostate cancer].

Diagnostic utility of serum markers and their relative values to prostatic volume were evaluated using Receiver Operator Characteristics Analysis (ROC analysis) in 173 patients who underwent ultrasound guided biopsy of the prostate gland. Seventy cases (40.5%) of prostate cancer were detected. As a whole, prostate specific antigen density (PSAD) and prostate specific antigen (PSA) were more useful than gammaseminoprotein density (GSMD), gammaseminoprotein (GSM) and prostatic acid phosphatase in diagnosing cancer judged by the area under the ROC curve denoting a test's diagnostic accuracy (p < 0.05). No significant difference was noted, however, between PSAD and PSA (p > 0.05). Prostate specific antigen density was more predictive for prostate cancer than PSA in a subgroup of patients with PSA levels of 2.0-10.0 ng/ml (p < 0.05). No advantage of PSAD was obtained in patients with intermediate PSA levels of 2.0-5.0 ng/ml or benign-feeling glands (p > 0.05). Higher sensitivity could be achieved by using Eiken PSA 2.0 ng/ml as a cutoff rather than the recommended value of 3.0 ng/ml. This helped to diagnose 5 more cases of prostate cancer who otherwise might have been missed if PSA cutoff of 3.0 ng/ml had been used. A PSAD cutoff of 0.15 has a sensitivity of 81.4%, a specificity of 87.4% and an accuracy of 85.0%. However, use of this cutoff for biopsy could result in unacceptable numbers of undiagnosed cases, including many potentially curable cancers. Though PSAD may enhance sensitivity and specificity in a certain group of patients, this gain is not sufficient to reliably define the group at highest risk of prostate cancer. Indication of biopsy should still be determined based upon PSA concentration rather than PSAD value.

Adult↗

[Clinical feature and quality of life of urinary diversion patients with bladder cancer].

A clinical survey was performed on 95 cases who were treated by total cystectomy with urinary diversion at our hospital between August 1971 and March 1992. Urinary diversions were classified by ureterocutaneostomy (Group I) in 27 patients, ileal or colon conduit (Group II) in 45 and continent urinary reservoir (Group III) in 23. The patients ranged in age from 29 to 76 with an average age of 60.6 year and the male to female ratio was 68 to 27. Histopathological typing of bladder cancers showed 82 cases of transitional cell carcinoma, 8 cases of squamous cell carcinoma, 4 cases of adenocarcinoma, and 1 mixed carcinoma with transitional cell carcinoma, squamous cell carcinoma and adenocarcinoma. At present, patients alive of Group I, II and III were 14, 27 and 16, respectively, totally 57 (60.0%) patients were alive. Five-year actuarial survival rates of Group I, II and III were 45.2%, 54.1%, and 56.8%, respectively. A questionnaire survey was carried out to assess the quality of life (QOL) of 57 alive patients. The analysis of replied questionnaire showed that even all patients of each groups adapted to the basic life activities after urinary diversion, though a step forward quality of life with hobby, travel and job were decreased postoperatively in 3 groups. We obtained results that the patients of Group III were more satisfactory with daily (bath) and social life (job) than the patients of Group I, II and preoperatively. We have a new comprehension of importance of enough informed consent and mental support to the urinary diversion patients preoperatively, and of a new operative procedure not to impair the QOL.

Adenocarcinoma↗