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Biomedical subjects

K Endo

Publications and source records attributed to K Endo.

At least 487 records · Page 27Linked to original sources

BE-23372M, a novel protein tyrosine kinase inhibitor. I. Producing organism, fermentation, isolation and biological activities.

BE-23372M, a novel protein tyrosine kinase inhibitor, was isolated from the culture broth of a fungus. The producing strain, F23372, was identified as Rhizoctonia solani, based on the cultural and morphological characteristics. The active principle was extracted from the mycelium with acetone and purified by solvent extraction, silica gel column chromatography and Sephadex LH-20 column chromatography. BE-23372M showed strong inhibitory activity against EGF receptor kinase with IC50 values of 0.02 and 0.03 microM on two different substrates, whereas IC50 values against protein kinase C and cAMP-dependent protein kinase were 4.5 and > 20 microM, respectively. The compound inhibited the growth of A431 human epidermoid carcinoma and MKN-7 human stomach cancer cell lines with IC50 values of 8 and 24 microM, respectively.

Amino Acid Sequence↗

Potentiated maturation with a high proliferating activity of acute promyelocytic leukemia induced in vitro by granulocyte or granulocyte/macrophage colony-stimulating factors in combination with all-trans retinoic acid.

All-trans retinoic acid (ATRA) induces differentiation of acute promyelocytic leukemia (APL), but the effect of cytokines regulating myeloid differentiation on ATRA-induced APL cells is poorly understood. In this study, maturation and proliferation of fresh APL cells were examined when induced in vitro by granulocyte or granulocyte/macrophage colony-stimulating factors (G-CSF or GM-CSF) in combination with ATRA. APL cells showed a low proliferating activity when induced by ATRA alone. In contrast, cells induced by G-CSF or GM-CSF alone showed increased DNA syntheses, the levels of which were not significantly affected by the combination of ATRA with CSFs. Interestingly, G-CSF or GM-CSF potentiated the capability of ATRA-induced cells to reduce nitroblue tetrazolium (NBT), while G-CSF or GM-CSF alone induced no NBT reduction. Furthermore, in several patients examined, APL cells induced by ATRA with G-CSF showed an increased activity of chemotaxis and CD11a expression. These findings suggest that G-CSF or GM-CSF can potentiate differentiation of ATRA-induced APL cells while stimulating their proliferating activity as well, and that G-CSF, rather than GM-CSF, may be a useful adjunct to promote ATRA-induced differentiation of APL.

Adolescent↗

[A case of severe measles encephalitis in a pregnant woman].

A 23-year-old woman in her 23rd week of gestation became febrile and then developed cutaneous eruption typical of measles on July 16, 1993. Two weeks prior to this, her 8-month-old daughter has developed measles. The woman became comatose in a few days and was admitted to our hospital where coma, flaccid paralysis of all four limbs and midbrain corectopia were apparent. High titers of anti-measles antibodies were found in the serum and cerebrospinal fluid. She received a 3-day course of pulse-dose intravenous methylprednisolone, however, without effect. Her consciousness gradually improved and after 1 month, subtle volitional movements were observed. However, fetal death was found and the fetus was removed by cesarean section. In MRI T2-weighted images, earlier in her illness, high signal intensity areas were scattered deeply in the cerebral white matter and the posterior limbs of the internal capsule. However, T1-weighted image was unremarkable. Marked, diffuse cerebral atrophy was noticed 3 months later by both CT and MRI, which was accompanied by wide spread high signal intensity areas around the lateral and fourth ventricles. Regarding the pathogenesis, there are two possibilities, i.e., her encephalitis was due to direct measles viral invasion into the CNS, or due to the autoimmune processes triggered by measles infection. Immune dysfunction known to occur during pregnancy might be responsible for the severity of encephalitis the patient suffered from. A recent increase in the number of adult measles infection might be an admonition that pregnant women are not exceptional to measles infection and that the infection could give rise to a severe form of measles encephalitis.

Adult↗

Improved clearance of radiolabeled biotinylated monoclonal antibody following the infusion of avidin as a "chase" without decreased accumulation in the target tumor.

UNLABELLED: The techniques of radioimmunoimaging and radioimmunotherapy suffer from prolonged high background radioactivity because intravenously injected antibodies remain in the circulation and in the organs far longer than necessary for effective binding to the target. To decrease background and increase radionuclide excretion without decreasing the dose of radioactivity delivered to the target tumor, we used radiolabeled biotinylated antibodies followed by a "chase" avidin injection. METHODS: A mouse monoclonal antibody, OST7 (IgG1), which reacts with human osteosarcoma, was biotinylated and labeled with 125I, 131I or 99mTc. Radiolabeled biotinylated OST7 (10 micrograms) was administered intravenously into nude mice bearing human osteosarcomas and 30 micrograms of avidin was injected intravenously 6 or 24 hr later. RESULTS: Following avidin injection in mice pretreated with radiolabeled biotinylated antibodies, radioactivity was promptly cleared from the blood and deposited in the liver and spleen, after which radioiodine was rapidly detached from the antibody and excreted in the urine. The tumor-to-blood ratios at 6 and 24 hr after the injection of 125I-labeled biotinylated OST7 increased compared with the values before the avidin chase without any loss of tumor radioactivity. Furthermore, the tumor-to-background radioactivity ratio was improved and better images were obtained more rapidly after the injection of radiolabeled biotinylated antibodies than with conventional immunoscintigraphy. CONCLUSIONS: This method may find application in clinical radioimmunoimaging, especially using short half-life radionuclides such as 99mTc and 123I.

Animals↗

Reversible functional asplenia. Autoimmune hemolytic anemia with thrombocytopenia in chronic lymphocytic leukemia.

An enlarged spleen failed to accumulate Tc-99m-labeled phytate, but it showed normal perfusion and uptake of labeled and heat-denatured red blood cells. A blood cell count demonstrated moderately low hemoglobin and hematocrit levels and a markedly low platelet count, and results of direct Coombs' and antiplatelet-antibody (IgG) tests were positive. Steroid therapy resulted in normal splenic function. This case demonstrates reversible functional asplenia caused by reticuloendothelial dysfunction secondary to pure splenic chronic lymphocytic leukemia.

Anemia, Hemolytic, Autoimmune↗

[Eye complications in atopic dermatitis].

Eye complications were studied in 240 cases of atopic dermatitis (age distribution 9 months to 40 years) hospitalized in the dermatology ward of our hospital. One hundred and thirty-four patients (55.8%) had at least one eye complication. Allergic conjunctivitis, cataracts, vernal conjunctivitis, retinal detachment, keratoconus, and retinal tears were detected in 28.3%, 17.9%, 2.1%, 1.3%, 1.3%, and 0.8%, respectively. Serum IgE levels and eye complications did not correlate. Routine ophthalmological examinations are recommended for patients with atopic dermatitis.

Adolescent↗

Schwannoma of the extremities: comparison of MRI and pentavalent technetium-99m-dimercaptosuccinic acid and gallium-67-citrate scintigraphy.

The diagnostic value of MRI and scintigraphy was studied in patients with Schwannomas of the upper or lower extremities. MRI (T1- and T2-weighted imaging), pentavalent 99mTc-dimercaptosuccinic acid and 67Ga-citrate scintigraphy were performed in 11 patients with 12 histologically proven benign Schwannomas. All six tumors with a maximum diameter > or = 3 cm showed marked accumulation of pentavalent 99mTc-dimercaptosuccinic acid, whereas they showed no uptake of 67Ga-citrate. MRI detected all of the tumors, and the lesions had a signal intensity equal to or slightly less than that of skeletal muscle on T1-weighted images and hyperintense to that of subcutaneous fat on T2-weighted images. MRI was superior to detect small Schwannomas of the extremities. A positive 99mTc-dimercaptosuccinic acid scan and a negative 67Ga-citrate scan however is useful to distinguish sarcoma with myxoid change from Schwannoma.

Adolescent↗

[Chondrosarcoma originating in the rib: a case report].

Chondrosarcoma originating in the rib is a rare disease. Although its pathological characteristics are believed to be mild, it is apt to recur and prognosis deteriorates in the absence of appropriate excision. The authors experienced a patient with a chondrosarcoma in the right 6th rib. The patient was a 49-year-old man who visited our hospital with a mass in the right anterior chest wall and chest pain. The patient underwent radical excision of the bony chest wall including the right 5th to 7th ribs. The resulting defect in the chest wall was restored with double-overlapping Marlex mesh. There has been no sign of recurrence to date, 6 years and 1 month postoperatively.

Bone Neoplasms↗

Effect of hyperthermia on tumor uptake of radiolabeled anti-neural cell adhesion molecule antibody in small-cell lung cancer xenografts.

UNLABELLED: This study was performed to examine the effect of hyperthermia on the intratumor accumulation of a monoclonal antibody (Mab) in an animal model. Mab NE150 (IgG1) recognizes the neural cell adhesion molecule (NCAM) expressed by human small-cell lung cancer (SCLC) cells. METHODS: Athymic mice inoculated with NCI-H69, an SCLC cell line, received an intravenous injection of 125I- and 111In-NE150 and the serial changes of the biodistribution were determined. Furthermore, athymic mice bearing NCI-H69 were either sham-treated or treated by a single hyperthermia at 42 degrees C or 43 degrees C for 1 hr, with the tumor-bearing leg in a water bath using pentobarbital anesthesia. Immediately after heating, the mice were given an intravenous injection of radiolabeled NE150, and the biodistribution was examined at 24 and 48 hr. RESULTS: NE150 localized well in the transplanted tumor when compared with a control Mab. In mice treated at 43 degrees C, there was a 1.34- to 1.67-fold increase in the tumor uptake of 125I- and 111In-NE150 compared to sham-treated mice at both 24 and 48 hr. In addition, a 1.84- to 2.22-fold increase of the tumor-to-blood ratio was demonstrated, since radiolabeled NE150 cleared faster from the circulation in the mice given hyperthermia. A histological study demonstrated the infiltration of neutrophils in the perivascular spaces, indicating an increase of tumor vascular permeability, which might be one of the main reasons for the enhancement of Mab uptake. CONCLUSION: Hyperthermia seems to be a potential method of achieving an increased tumor accumulation of Mab in the radioimmunotargeting of SCLC.

Animals↗

The radiologic presentation of Osler-Weber-Rendu disease of the liver.

A case of Osler-Weber-Rendu disease with extensive hepatic arteriovenous fistulation is described in detail. Hemodynamic and imaging data indicated hepatic artery to hepatic vein shunting. Enhanced magnetic resonance imaging demonstrated the existence of arteriovenous fistulas by virtue of simultaneous enhancement of hepatic arteries and veins. Embolization treatment was not indicated because the patient was asymptomatic despite cardiac high output.

Arteriovenous Fistula↗

Quantitative EEG in patients with presenile and senile dementia of the Alzheimer type.

EEG data obtained from 27 patients with presenile Alzheimer's disease (AD) and 28 patients with senile dementia of the Alzheimer type (SDAT) were compared with data from 30 age- and sex-matched controls. Both patient groups exhibited more pronounced delta and theta activity and less prominent alpha and beta activity than the controls. AD, however, was accompanied by more severe slowing than SDAT. The slowing was distributed in the left temporal and frontal regions in AD, and bilaterally in the frontal regions in SDAT. As the severity of the dementia increased, delta activity alone increased in AD, whereas, there were significantly greater increases in both delta and theta activity and decreases in alpha and beta activity in SDAT. These EEG differences appear to be related to the degree of brain damage and the speed of progression of the disease process.

Aged↗

Treatment of small-cell lung cancer xenografts with iodine-131-anti-neural cell adhesion molecule monoclonal antibody and evaluation of absorbed dose in tissue.

UNLABELLED: Human small-cell lung cancer (SCLC) is considered a feasible target for immunotherapy using a radiolabeled monoclonal antibody (Mab). A murine Mab, NE150 (IgG1), reacts with the neural cell adhesion molecule, which is identical to cluster 1 antigen of SCLC. METHODS: To estimate their therapeutic effects, NE150 and an isotype-matched control Mab were labeled with 131I and administered intravenously as a single dose into athymic mice inoculated with a NCI-H69 SCLC xenograft. The absorbed dose in organs was also examined based upon a long-term biodistribution study of 131I-NE150. RESULTS: Tumors (initial volume 563.4 +/- 223.5 mm3) treated with 11.1 MBq (300 microCi) of 131I-NE150 diminished and became invisible at days 30-33, demonstrating a 60-day mean growth delay to reach a tripled initial volume compared with sham-treated tumors. Cumulative absorbed doses were estimated to be 2310, 410, 500, 330, and 790 cGy for the tumor, liver, kidney, spleen and lung, respectively. CONCLUSION: Iodine-131-NE150 had potent therapeutic effects against SCLC transplants in athymic mice, however, careful assessment of the side effects, improvement of radioiodination and chimerization of the Mab might be necessary to achieve efficient targeting in clinical therapeutic applications.

Antibodies, Monoclonal↗

[Clinical usefulness of thallium-201 chloride in the diagnosis of tumors (I)--Evaluation in brain tumors].

Forty-eight patients with suspected brain tumor were studied to evaluate the clinical efficacy of Thallium-201 (201Tl) SPECT. 201Tl scintigrams showed abnormal accumulation in 24/26 (92.3%) and 9/14 (64.3%) of patients with malignant and benign tumors, respectively. 201Tl tended to be retained more prominently in malignant brain tumors than in benign ones. The lesion-to-normal ratios (L/N ratios) of 201Tl demonstrated significant correlation with those of 18F-FDG (n = 5, r = 0.90, p = 0.044). L/N ratios were higher in patients with recurrent tumors than those with necrotic lesions (3.33 +/- 0.81 and 1.73 +/- 0.81, respectively, p = 0.0123). The positive predictive value of L/N ratios > or = 2.5 for diagnosing as recurrence and L/N ratios < 2.5 as necrosis were 83.3% and 100%, respectively. These results suggest that 201Tl scintigraphy may be useful to determine the malignancy of brain tumors and to differentiate recurrence from necrosis after therapeutic procedures.

Adolescent↗

[Use of monoclonal antibodies for the immuno-imaging of cancers].

Monoclonal antibodies are expected to carry radio-nuclides selectively to cancer tissues and to offer antigen-specific diagnosis and/or therapy of cancer. Monoclonal antibodies tagged with indium (111In) and technetium (99mTc) are clinically used for the localization of malignant melanoma, colorectal and ovarian cancer. They have detected about 80% of tumors, tumors missed by conventional diagnostic methods and tumors in patients with normal serum tumor marker levels. Acute or subacute toxicity was not observed. However, human anti-murine antibodies (HAMA) were detectable in sera of some cases after receiving radiolabeled monoclonal antibodies. Development of protein engineering has made it possible to produce humanized antibodies, which are expected to diminish the HAMA response. The same monoclonal antibodies are also employed for therapy of some cancers using iodine (131I), yttrium (90Y) and rhenium (186Re) labeled antibodies.

Animals↗

Increased uptake of iodine-131 in metastases of differentiated thyroid carcinoma associated with less severe hypothyroidism following total thyroidectomy.

BACKGROUND: In an attempt to determine possible factors affecting the efficacy of iodine-131 (I-131) treatment for metastatic thyroid carcinoma, the authors focused their efforts on thyroid functions after total thyroidectomy. METHODS: Between 1980 and 1991, 47 patients with lung metastases of differentiated thyroid carcinoma were treated with I-131. Relationships of the images on post-therapy scans with various clinical features were studied. RESULTS: Among them, 28 (59.6%) showed I-131 uptake in the metastases on post-therapy scans. Younger patients had lesions that concentrated more radioactive iodine than did those of older patients. The amount of I-131 concentrated in the metastatic lesions correlated with serum triiodothyronine (T3), thyroxine (T4), and thyroglobulin levels and inversely with serum thyroid-stimulating hormone (TSH) levels determined at the time of therapy. Serum T3 and T4 levels were significantly higher in 28 patients with positive scans than in 19 patients with negative scans. Most patients who had metastases with markedly increased radioactivity were euthyroid or mildly hypothyroid, suggesting that thyroid hormones produced by tumor masses compensated for severe hypothyroidism after total thyroidectomy, and showed favorable responses to the treatment. In three patients successfully treated, decreases in serum thyroglobulin levels and the size of metastatic lesions were accompanied by the development of severe hypothyroidism. CONCLUSIONS: The presence of a large amount of metastatic functioning thyroid tissues responsive to I-131 treatment can be suspected in patients with less severe hypothyroidism after total thyroidectomy.

Adenocarcinoma↗

[Clinical usefulness of 123I-IMP scintigraphy in the diagnosis of bone metastases from hepatocellular carcinoma: comparison with 99mTc-MDP bone scintigraphy].

The diagnostic value of N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) scintigraphy was evaluated in 12 patients with 20 bone metastases from hepatocellular carcinoma, in comparison with 99mTc-methylene diphosphonate (99mTc-MDP) bone scintigraphy. Sixteen lesions (80%) were detected by 123I-IMP scintigraphy, whereas four lesions (two lesions in the rib and two lesions after a radiation of 40 Gy) were missed. Of 16 lesions demonstrated as areas of increased uptake in 123I-IMP scan, only eight (50%) showed an increased pattern of uptake in 99mTc-MDP bone scintigraphy. In conclusion, 123I-IMP is a promising radiopharmaceutical for the detection of bone metastases from hepatocellular carcinoma.

Amphetamines↗

Mast cell activation by pedicellarial toxin of sea urchin, Toxopneustes pileolus.

Pedicellarial toxin, partially purified from the sea urchin Toxopneustes pileolus, dose-dependently and time-dependently caused histamine release from rat peritoneal mast cells. Pedicellarial toxin induced a rapid initial rise in [Ca2+]i within several seconds which was followed by a further slower increase of [Ca2+]i (second rise). The toxin induced a dose-dependent formation of inositol 1,4,5-triphosphate (IP3) as well as the histamine release in mast cells. Furthermore, the toxin stimulated phosphoinositide-specific phospholipase C (PI-PLC) activity in mast cell membranes. 2-Nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC), a PLC inhibitor, inhibited the activation of PI-PCL induced by pedicellarial toxin. Cholera toxin inhibited pedicellarial toxin-induced histamine release, whereas pretreatment of pertussis toxin failed to inhibit it. These results suggest that pedicellarial toxin from T. pileolus activates PI-PCL and the stimulation of PI turnover may lead to the release of IP3 into the cytoplasm, resulting in histamine release from rat mast cells.

Animals↗