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Biomedical subjects

K Tadokoro

Publications and source records attributed to K Tadokoro.

At least 19 recordsLinked to original sources

[Clinical evaluation of hepatic scintigraphy using 99mTc-GSA].

Functional hepatic imaging was performed using 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA), a radiolabeled ligand that reacts specifically to the asialoglycoprotein receptor that resides at the plasma membrane of hepatocytes, in 21 patients: five with chronic active hepatitis (CAH), 14 with compensative liver cirrhosis (LC), one with chronic inactive hepatitis and one with acute hepatitis. The former two diseases were mainly investigated. Serial liver images were acquired at the rates of 10 sec/frame for 0-5 min and 2 min/frame for 6-30 min after the injection of 99mTc-GSA, and the images were compared with 99mTc-phytate images in 2 patients with CAH and 11 with LC, and those with portal scintigrams using 123I-iodoamphetamine (IMP) in 3 patients with LC. The images using 99mTc-GSA were in better agreement with hepatic function than those using 99mTc-phytate, and with the findings of portal scintigraphy using 123I-IMP. LHL15 (liver/liver and heart radioactivities at 15 min after the injection of 99mTc-GSA) correlated with the hepaplastin test (r = 0.978 in CAH, and r = 0.544 in LC), indicators of hepatic reserve. These results suggest that liver scintigraphy using 99mTc-GSA might be a useful method for evaluating liver function.

Adult

Genomic organization of the human WT1 gene.

We have analyzed the genomic structure of the human WT1 gene, one of the recessive oncogenes for Wilms' tumor at chromosome 11p13. By analyses of three cosmids covering the WT1 gene as well as products generated by polymerase chain reaction, cleavage sites for 10 restriction enzymes were mapped in a region of about 80 kb, and the positions of 10 exons were defined. We also mapped two polymorphic sites for TaqI. Our genomic map will be useful to analyze DNA abnormalities sometimes found in the tumors, as well as loss of heterozygosity.

Base Sequence

Intragenic homozygous deletion of the WT1 gene in Wilms' tumor.

One example of intragenic homozygous deletion of the WT1 gene on chromosome 11p13 was found after screening 42 samples of Wilms' tumor DNA from Japanese patients. After construction of a restriction map for the genomic sequence covering the 3' half of the gene, the deletion was analysed at the nucleotide sequence level. The deletion occurred in the patient's germline on his paternal chromosome, and most of the short arm of his maternal chromosome 11 was subsequently lost in the tumor. The size of the deletion was about 8 kb, removing exons 6 and 7 and resulting in premature termination. The deletion seemed to be created by recombination between short homologous sequences found in an Alu repeat, with a 16-bp duplication left at the junction. This case conforms to a two-hit model for the genesis of a certain group of tumors, and supports the hypothesis that WT1 is one of the recessive oncogenes responsible for Wilms' tumor.

Base Sequence

[Evaluation of interstitial shadows by thin slice computed tomography].

We developed a method for evaluation of interstitial shadows by thin slice computed tomography (CT). We studied thirty-seven cases with interstitial shadows confirmed by thin slice CT, and 13 normal cases. Thin slice CT was scanned on 3 levels: 1) at the aortic arch, 2) about 2 cm below the carina, and 3) about 1 cm above the right diaphragm. Each level was scanned bilaterally to produce 6 regions of interest (ROI); CT numbers were recorded from each ROI. CT numbers ranging from -1000 to 100 Hounsfield units (H.U.) were classified into 4 different bands, -1000 - (-900) H.U. (low band), -900 - (-750) H.U. (medium low band), -750 - (-500) H.U. (medium high band), and -500 - 100 H.U. (high band), for cases with interstitial shadows and for normal cases. We calculated the prevalence of CT numbers in each band for both normals and subjects with interstitial shadows. Compared to the normals, subjects with interstitial shadows showed fewer pixels in the medium low band and more pixels in the medium high and high bands. Furthermore, the prevalence of CT numbers in each band correlated with %TLC, %VC, and pulmonary diffusing capacity. We conclude that thin slice CT is a useful method for evaluation of the extent and characteristics of interstitial shadows.

Alveolitis, Extrinsic Allergic

Enzymatic dispersion of mast cells from human sinus mucosa: characterization of histamine release and its comparison with chopped fragments of the tissue.

Functional characteristics of mast cells in chopped fragments from sinus mucosa, which was dissected from patients with chronic sinusitis, were compared with those from dispersed cells prepared by enzymatic treatment. The results obtained in this study were the following. (1) Both chopped fragments and dispersed cells released histamine in a dose-dependent manner when incubated with anti-IgE. However, higher histamine release was always observed in dispersed cells. (2) Although no differences in the ability to reduce histamine release with salbutamol or forskolin could be observed between chopped fragments and dispersed cells, staurosporin and p-bromophenacyl bromide were more active on dispersed mast cells than chopped fragments. (3) Passive sensitization of dispersed cells with an allergic serum containing IgE to mite could be achieved only after elution of IgE on the cells with lactic acid.

Acetophenones

Topical thrombin-induced IgE-mediated anaphylaxis: RAST analysis and skin test studies.

Bovine topical thrombin (BTT) is a heterologous plasma thrombin concentrate that has been frequently used for the hemostasis since the 1940s. Recently, three patients in Japan went into shock after the topical application of BTT at lesion sites, and two of these patients had received BTT repeatedly. The clinical symptoms and the increased anti-BTT percent RAST counts suggest that these reactions were shock mediated by anti-BTT IgE antibodies. The RAST-inhibition analysis suggested that the antigenic substance(s) were bovine-specific moiety(ies) mainly involved in the contaminant rather than bovine thrombin itself. The skin tests were studied to predict such allergic reactions. The intracutaneous test provoked nonspecific reactions even at the low concentrations of BTT. The prospective study on the predictive value of the prick test with 1000 U/ml (1 mg/ml) of BTT in 192 patients suggested that it is useful to detect highly sensitive patients. In addition, the increased levels of anti-BTT IgE antibodies in patients 1 month after the single administration of BTT suggested the immunogenicity of the topical application of BTT.

Administration, Topical

Food-dependent, exercise-induced anaphylaxis: a study on 11 Japanese cases.

Eleven patients with food-dependent, exercise-induced anaphylaxis were studied. Seven patients experienced anaphylactic symptoms only after eating certain foods, such as shellfish, wheat, and grape before exercise. In the remaining four patients, no specific food could be identified, but the act of eating itself predisposed to anaphylaxis. Their anaphylactic symptoms were all clearly distinguished from cholinergic urticaria by history. Patients who developed anaphylactic symptoms before 20 years of age (N = 7) were atopic themselves or had atopic first-degree relatives. Six patients had increased serum IgE levels, and IgE antibodies against the causative food allergens were detected by the skin prick test or RAST in four cases. In contrast, patients who developed the symptoms after 30 years of age (N = 4) appeared to have a less atopic background, and IgE levels were within normal range except in one case. Three of four patients in the latter group developed symptoms after ingesting food made of wheat followed by exercise. All patients were sensitive to wheat as determined by the skin prick test. In six of 11 patients, a considerable rise in plasma histamine concentration was observed after exercise challenge with treadmill alone, and food intake followed by exercise induced a further increase in one patient.

Adolescent

Detection of burst-promoting activity in spleens of myeloproliferative sarcoma virus-infected mice using serum-free cultures.

Myeloproliferative syndrome was induced in adult DBA/2 mice by inoculation with myeloproliferative sarcoma virus (MPSV) and Friend murine leukemia virus (F-MuLV) as a helper virus. On day 26 after infection, the spleen weighed a maximum of 2.0 g (about 30 times the control weight). Assay of multipotent stem cells in vitro showed that the more enlarged spleens contained an increased number and concentration of mixed colony-forming units (CFU-mix) (at maximum, 11 times higher than the control). When the supernatant of cultured spleen cells was added to a serum-free bone marrow cell culture with or without erythropoietin (Epo) for detection of burst-promoting activity (BPA), it enhanced erythroid mixed colony (E-mix) formation only in the presence of Epo (p less than 0.05). Even when addition of Epo was delayed, it still induced a significant number of E-mix (p less than 0.05). These findings rule out a mimic effect of Epo resembling BPA and indicate the presence of BPA in the spleen. The culture supernatant also supported the proliferation of interleukin 3 (IL-3)-dependent 32Dcl cells. Therefore, although purification of the BPA substance has not yet been accomplished, BPA in the supernatant seems to depend on the presence of IL-3, which is known to be one of the factors stimulating multipotent hemopoietic stem cells. The presence of BPA- or CFU-mix-stimulating activity in the spleen after infection might be responsible for the development of panmyelosis, which is a characteristic of MPSV-induced myeloproliferative syndrome.

Animals

[The diagnostic value of a new whole blood histamine release test using paper disc-coupled antigens--results compared with intracutaneous test, RAST, and eye test].

We have developed a novel histamine release test (HR) using whole blood and antigen-coupled RAST paper discs, for the screening of allergens rather in a short time with a small amount of blood. Histamine was determined by a RIA kit. In order to evaluate the diagnostic value, the results of the test were compared with those of RAST, intracutaneous tests, and eye tests in 45 allergic patients. HR correlates better with RAST than intracutaneous test in almost all antigens. The closest positive correlation with the other tests was seen in mite allergen, followed by pollen, foods and mould spores in that order. When the HR was positive for house dust, 100% of the patients were also positive for the eye test, which is reported to closely correlate with bronchial provocation tests. HR seemed to be a useful test not only for the screening but also for the determination of pathogenic allergens.

Adolescent

Histamine release with a solid-phase-coupled allergen.

Mite allergen was coupled to Sepharose, paper disk or microcrystalline cellulose, and the immobilized allergen was used for histamine release assay in human leukocytes. In terms of the spontaneous release and the reproducibility, the histamine release assay using immobilized allergen was comparable to that using soluble allergen. Histamine release increased progressively with the concentration of the immobilized allergen up to maximal release of histamine which persisted with further increase in immobilized allergen. Histamine release with soluble allergen decreased at higher concentrations of the allergen. The concentration of immobilized allergen required for maximal histamine release was the same as that with soluble allergen, but the maximal release with immobilized allergen was always about 20% lower than that with soluble allergen. Histamine release was not dependent on the density of allergen molecules on Sepharose beads. Although there was a significant correlation between histamine release obtained with a commercial disk, with a disk prepared in our laboratory, and with soluble allergen, the magnitude of the release by both assays using a paper disk was reduced significantly.

Allergens

[Clinical evaluation of renoscintigraphy using 123I-orthoiodohippurate--comparison with 131I-OIH and measurement of the effective renal blood flow].

Renoscintigraphy using 123I-orthoiodohipprate (123I-OIH) was conducted, and the dynamic imaging study results and the renograms were analyzed. The results using 123I-OIH were compared with those using 131I-OIH in 22 of 33 patients. Measurement of the effective renal blood flow (ERBF) was also performed using 123I-OIH by the single blood-sample method. 123I is a more suitable nuclide for gamma-camera scintigraphy than 131I in terms of physical characteristics, and a larger dose of 123I-OIH is possible than 131I-OIH because of its lesser radiation. These are the reasons why clearer dynamic images of the blood flow phase, functional phase and excretion phase can be obtained. These make possible diagnoses associated with the organic changes and functions. No essential differences could be found in the functional study results of renogram between the two drugs because on the nuclide of 131I is replaced by 123I, but a renogram with less statistical noise could be obtained using 123I-OIH than 131I-OIH. The radiation dose of 123I-OIH is less than that of 131I-OHI, and clearer dynamic images and functional indexes can be easily obtained in scintigraphy using 123I-OIH. It is concluded that 123I-OIH is a useful radiopharmaceutical for renal examination, and it should replace 131I-OIH.

Adolescent

[3 cases of food-dependent exercise-induced anaphylaxis in which aspirin intake exacerbated anaphylactic symptoms].

Exercise-induced anaphylaxis (EIAn) is a distinct form of physical allergy. As one of the predisposing factors of EIAn, food intake is often cited, and such cases are classified as food-dependent EIAn. Another factor reported is the administration of drugs. Recently we had 3 patients with food-dependent EIAn who showed more severe symptoms when they took aspirin orally. None of them had shown symptoms when they took aspirin alone. Symptoms were provoked only when they took aspirin for common cold, headache or toothache followed by certain foods and exercise. Two out of the 3 patients had experienced food-dependent EIAn before. However, after taking aspirin, their anaphylactic symptoms were more severe with more slight degree of exercise. Results of exercise challenge by treadmill showed that exercise alone induced an increase in plasma histamine concentrations in 2 out of the 3 patients 5 to 15 minutes after the challenge. These data suggest the possibility that our patients have an increased histamine releasability from mast cells responding to exercise, and that aspirin intake might enhance the process.

Adult

Enhancing effect of suspended particulate matter on the IgE antibody production in mice.

Suspended particulate matter (SPM), suspended in the polluted environmental atmosphere, are perpetually inhaled into the human body and are considered to have profound effects on human health. This study investigated the enhancing effect of SPM on the IgE antibody production in mice. The IgE antibody responses in mice immunized with intranasal administration of ovalbumin (OA) plus SPM at 3-week intervals were higher than responses in the animals immunized with OA alone. When the dose of OA administered as an antigen was 0.25 microgram, the time course and magnitude of enhancement by SPM was comparable to those by killed Bordetella pertussis, a common adjuvant. SPM had an enhancing effect on IgE antibody production even in a small dose such as 0.25 microgram administered at 3-week intervals. The possibility cannot be excluded that the natural exposure of humans to SPM in the environmental atmosphere may explain the high prevalence rate of allergic rhinitis caused by pollens in polluted districts in Japan.

Adjuvants, Immunologic

Activation of oncogenes in human oral cancer cells: a novel codon 13 mutation of c-H-ras-1 and concurrent amplifications of c-erbB-1 and c-myc.

By NIH3T3 transfection assay in conjunction with in vitro transient neomycin selection, activated c-H-ras-1 oncogenes were detected in two squamous cell carcinoma cell lines, ZA and HOC-313, newly established from human oral cancer patients. ZA had a point mutational activation at the 13th codon, this activation of c-H-ras-1 being novel in human cancer cells, while HOC-313 appeared to have an activation at the 12th codon. In ZA, 16- to 32-fold amplification of the EGF receptor gene, c-erbB-1 and a few-fold amplification of c-myc were detected. The significance of these findings is discussed in relation to multistep carcinogenesis in human cells.

Aged

[Dynamic local cerebral circulation study in patients with cerebral diseases--using 99mTc-HSA-D mainly compared with 99mTc-HSA].

We have been using 99mTc-RBC and 99mTc-HSA for cerebral angiography and measurement of the local cerebral blood volume (LCBV) and cerebral/peripheral hematocrit ratio (alpha). 99mTc-HSA, however, has a problem of poor stability in the blood. We conducted basic and clinical studies on 99mTc-HSA-D, a ready-to-use preparation with good stability in the blood. We measured the regional cerebral circulation dynamics in patients with cerebral diseases in comparison with 99mTc-RBC and 99mTc-HSA. 99mTc-HSA-D and 99mTc-RBC showed more than a 90% retention ratio in the blood 60 min after administration, and good SPECT images were obtained using these two pharmaceuticals. On the contrary, 99mTc-HSA was unstable and its retention ratio was 60s% 60 min after administration. 99mTc-HSA does not provide good SPECT images due to free 99mTcO4- which seems to be liberated from 99mTc-HSA in the body, etc. There were no adverse reactions or abnormal laboratory findings caused by the 99mTc-HSA-D administration in any of the patients. Based on these results, it is surmised that 99mTc-HSA-D is clinically useful for measurement of the cerebral blood volume and cerebral/peripheral hematocrit ratio (alpha).

Adult