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Biomedical subjects

K Endo

Publications and source records attributed to K Endo.

At least 451 records · Page 25Linked to original sources
PubMed1994

Evidence for the uptake of a vitamin D analogue (OCT) by a human carcinoma and its effect of suppressing the transcription of parathyroid hormone-related peptide gene in vivo.

The present study was undertaken to clarify the pharmacokinetics of 22-oxa-1,25-dihydroxyvitamin D3 (22-oxa-1,25-(OH)2D3, OCT), a vitamin D3 analogue with little calcemic activity, and its effect on the transcription of parathyroid hormone-related peptide (PTHRP) gene in nude mice bearing a human carcinoma (FA-6) associated with humoral hypercalcemia. FA-6 tumor expressed vitamin D receptor (VDR) mRNA, and its nuclear extract contained a specific and saturable 1,25-(OH)2D3 binding activity. Although [3H]OCT administered intravenously into FA-6 tumor-bearing nude mice was cleared from the circulation more rapidly than [3H]1,25-(OH)2D3, the uptake of [3H]OCT into the tumor tissue, relative to the radioactivity in the circulation, was greater than that of [3H]1,25-(OH)2D3. Intravenous or oral administration of OCT reduced the steady-state levels of PTHRP mRNA in FA-6 tumor, and nuclear run-off assays demonstrated that the effect of OCT on PTHRP gene expression occurred at a transcriptional level. RNase mapping analysis revealed that both upstream and downstream promoters of the human PTHRP gene were down-regulated by OCT. Finally, OCT exerted a preventive as well as therapeutic effect on cancer-associated hypercalcemia with a marked prolongation of the survival time in tumor-bearing animals. These results suggest that OCT is effectively taken up by a VDR-positive human carcinoma in vivo and has a therapeutic potential for cancer-associated hypercalcemia through suppression of PTHRP gene transcription.

Animals↗
PubMed1994

Expression of glutathione S-transferase-pi and sensitivity of human gastric cancer cells to cisplatin.

BACKGROUND: The authors examined the correlation between the expression of glutathione S-transferase-pi (GST pi) and the sensitivity of gastric cancer to anticancer agents. METHODS: In 62 human gastric carcinomas, the expression of GST pi was immunohistochemically evaluated, and sensitivity to the anticancer drugs, cisplatin (CDDP), doxorubicin (DXR) aclacinomycin A (aclarubicin), (ACR), 5-fluorouracil (5-FU), mitomycin C (MMC) and carboquone (carbazilquinon) (CQ) was examined using the in vitro succinate dehydrogenase inhibition test. The authors used the Chinese hamster ovary (CHO) cell line and its variant CDDP-resistant cell line C/CDP-2, and they analyzed the relationship among CDDP-sensitivity, mRNA expression, and immunohistochemical staining. RESULTS: Immunohistochemically detected GST-pi-positive tumors were noted in 35 of 62 excised tumors. There was no significant correlation between GST-pi expression and clinicopathologic features or prognosis. The succinate dehydrogenase activity of each drug for tumors, with regard to negative or positive GST-pi, was 34.9 plus or minus 13.7% and 46.0 plus or minus 22.0% for CDDP, with a significant statistical difference (P < 0.05). However, there was no statistical difference for the other drugs tested. C/CDP-2 cells showed a lower sensitivity to CDDP, a higher expression of mRNA for GST pi and a stronger immunohistochemical staining than CHO cells. CONCLUSIONS: The overexpression of GST-pi is significantly related to the sensitivity of gastric cancer to CDDP.

Aclarubicin↗
PubMed1994

Iron accumulation in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkeys.

The mechanism of abnormal iron accumulation in the substantia nigra (SN) pars compacta of patients with Parkinson's disease (PD) is unknown. To explore this question, we made a hemiparkinsonism model in monkeys by injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the caudate or putamen on one side, and compared iron content in the SN and other basal ganglia structures by histochemistry. The injected side, especially the SN pars compacta, showed a marked increase in iron staining. Our study indicates that an injury to the nigrostriatal system by MPTP injection can induce iron accumulation in the SN.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Trinucleotide repeat length and rate of progression of Huntington's disease.

The Huntington's disease gene contains an expanded unstable (CAG)n repeat, and the repeat lengths have been shown to correlate with the age of onset. Using detailed clinical scales, we evaluated the rate of progression of Huntington's disease and its relationship to the number of triplet repeats. We found significant positive correlation between the rate of progression of clinical symptoms (both neurological and psychiatric) and CAG repeat length. These data suggest an important role of expanded trinucleotide repeat length in affecting the pathological process during the entire course of Huntington's disease.

Base Sequence↗
PubMed1994

Dissociation in serum CA125 concentrations measured by different monoclonal antibodies.

The new immunoradiometric assay for CA125 (CA125II assay) uses the monoclonal antibody M11 as an immunoadsorbent. The epitope recognized by M11 is different from the OC125 epitope. Monoclonal antibodies 130-22 and 145-9 recognize an epitope designated as CA130 on the molecule expressing the OC125 epitope. Similarity of M11 epitope to the epitope of anti-CA130 antibodies and dissociation of antigen levels measured by the original CA125 assay and new CA125II assay were examined. Anti-CA130 antibodies partially competed with M11 for the M11 epitope. Among more than 20,000 serum samples we found 12 patients in whom the serum CA125 concentration measured by the CA125II assay was different from that measured by the original assay. In 11 out of 12 patients the CA125 concentration was moderately or extremely high by the original assay but very low by the CA125II assay. Eight of the 11 patients had benign disease, one had no apparent disease and two had cancer. The antigen level determined by CA130 assay was very low in all the 11 patients. In one patient the CA125II assay showed a higher antigen level than the original assay or CA130 assay. The heterogeneity of the epitope expression could cause the dissociation of CA125 levels measured by the different monoclonal antibodies.

Adult↗
PubMed1994

Preparation and clinical evaluation of technetium-99m dimercaptosuccinic acid for tumour scintigraphy.

We describe a simple method of pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] preparation for the imaging of medullary carcinoma of the thyroid using commercially available kits. 99mTc(V)-DMSA is available at high pH (approximately 7.5) by adding NaHCO3 solution in the presence of a small amount of reducing agent (SnCl2). On the other hand, trivalent 99mTc-DMSA [99mTc(III)-DMSA] can be obtained at low pH (below 3) in the presence of an excess amount of reducing agent. In the clinical evaluation of a patient with a medullary carcinoma of the thyroid, only 99mTc(V)-DMSA revealed an area of intense accumulation.

3-Iodobenzylguanidine↗
PubMed1994

Second-order vestibular neuron morphology of the extra-MLF anterior canal pathway in the cat.

Second-order vestibular neurons form the central links of the vestibulo-oculomotor three-neuron arcs that mediate compensatory eye movements. Most of the axons that provide for vertical vestibulo-ocular reflexes ascend in the medial longitudinal fasciculus (MLF) toward target neurons in the oculomotor and trochlear nuclei. We have now determined the morphology of individual excitatory second-order neurons of the anterior semicircular canal system that course outside the MLF to the oculomotor nucleus. The data were obtained by the intracellular horseradish peroxidase method. Cell somata of the extra-MLF anterior canal neurons were located in the superior vestibular nucleus. The main axon ascended through the deep reticular formation beneath the brachium conjunctivum to the rostral extent of the nucleus reticularis tegmenti pontis, where it crossed the midline. The main axon continued its trajectory to the caudal edge of the red nucleus from where it coursed back toward the oculomotor nucleus. Within the oculomotor nucleus, collaterals reached superior rectus and inferior oblique motoneurons. Some axon branches recrossed the midline within the oculomotor nucleus and reached the superior rectus motoneuron subdivision on that side. Since these neurons did not give off a collateral toward the spinal cord, they were classified as being of the vestibulo-oculomotor type and are thought to be involved exclusively in eye movement control. The signal content and spatial tuning characteristics of this anterior canal vestibulo-oculomotor neuron class remain to be determined.

Animals↗
PubMed1994

Alkaline phosphatase isozymes of serum and urine and urinary protein in young men before and after running 3 km.

Urine samples were collected from seven healthy male students 1 h before (control fraction) and 5-15 min (5-15 min fraction), 1 h (1-h fraction) and 3 h (3-h fraction) after running 3 km at a perceived exertion equal to approximately 15-17 Borg's scale. Venous blood was also collected from the subjects 1 h before and 1 h after the run. Urine was studied by measuring protein excretion, patterns of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of proteins, total alkaline phosphatase (ALP) excretion, intestinal alkaline phosphatase (IAP) excretion and ALP isozyme analysis by PAGE. Serum ALP was studied by measuring the total ALP activity and isozyme analysis by PAGE. The following results were observed: firstly, an increase was seen in the excretion of total protein, total ALP and IAP after the exercise. Statistical significance was seen in the first two of these parameters; secondly, albumin was the only detectable protein band in the control, 5-15 min and 3-h fraction by SDS-PAGE; thirdly, no significant changes were seen in total ALP activity and ALP isozymes in the serum; and fourthly, three to five ALP bands (bands 1, 2, 3, 4 and 5, from the cathodal side) were detected in the zymograms of urinary ALP. Bands 1-3 were high molecular mass ALP. Bands 4 and 5 were intestine-like and liver-like ALP, respectively. An increase of ALP activity of high molecular mass ALP and/or decrease of that of band 5 or appearance of band 4 were seen in the 1-h fraction, in comparison to the control fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Scintigraphic detection of neural-cell-derived small-cell lung cancer using glioma-specific antibody.

Radiolabeled GA-17, a murine monoclonal antibody that reacts specifically with glioma cells, bound to a small-cell lung cancer (SCLC) cell line NCI-H69 derived from neural cells, both in vitro and in vivo. The affinity constant of GA-17 F (ab')2 fragment binding to NCI-H69 was 1.02 x 10(8)/M while that to the glioma cell line U87MG was 1.22 x 10(8)/M. Iodine-125-labeled GA-17 F(ab')2 fragments injected i.v. localized well in NCI-H69 cells xenografted in nude mice. The percentage of the injected dose per gram accumulated in the xenografted tumor was 6.87 +/- 1.34% g-1 (mean +/- SD, n = 5) 24 h after injection. On the other hand, control monoclonal F(ab')2 fragments accumulated in the xenografted tumor at 0.75 +/- 0.30% g-1. The tumor-to-blood ratio was 1.8 for NCI-H69, while that of control F(ab')2 was 0.60. In conclusion, the radiolabeled GA-17 F(ab')2 fragment is expected to be useful clinically to visualize the small-cell lung cancer and in radioimmunotherapy.

Animals↗
PubMed1994

Cytogenetic study of a severe case of Pallister-Killian syndrome using fluorescence in situ hybridization.

Usually, the supernumerary isochromosome 12p characterizing Pallister-Killian syndrome patients was detected in cultured skin fibroblasts but not in cultured blood lymphocytes. The proband of this study was a one-day-old female, who presented with major clinical characteristics of the Pallister-Killian syndrome, and had severe malformations in the form of anal atresia, cleft palate, and severe laryngomalacia. Chromosome preparations from cultured blood lymphocytes and skin fibroblasts, as well as buccal smears, from this patient were analyzed by fluorescence in situ hybridization (FISH) using a chromosome 12-specific alpha satellite probe. The proportions of cells showing positive signals for i(12p) in these samples were found to be 20, 62.5, and 70%, respectively. Repeated FISH studies of buccal smears from this patient showed considerable decreases in the proportions of i(12p) containing cells to 40% at one year of age and to 32% at the age of one year and five months. The decline in the percentage of i(12p)-containing cells in buccal smears with aging supports the concept of in vivo loss of the marker during repeated cell division.

Abnormalities, Multiple↗
PubMed1994

Solitary muscular sarcoidosis: CT, MRI, and scintigraphic characteristics.

Scintigraphy using gallium-67 (67Ga) citrate and penvaralent technetium-99m dimercaptosuccinic acid ([99mTc(V)]DMSA) and other radiological examinations were performed in three patients with solitary muscular sarcoidosis who had tumor-like muscular lesions. Although distinction from other invasive soft tissue tumors was difficult using plain and enhanced computed tomography and magnetic resonance imaging, marked uptake of 67Ga and moderate uptake of [99mTc(V)]DMSA were shown at the sites of granulomatous inflammatory lesions of sarcoidosis. Both 67Ga and [99mTc(V)]DMSA scintigraphy could be of value in the diagnosis and detection of distribution of granulomas of sarcoidosis in the soft tissue and in determining the appropriate region for biopsy.

Adult↗
PubMed1994

131I-metaiodobenzylguanidine therapy for malignant pheochromocytoma.

131I-metaiodobenzylguanidine (MIBG) therapy was given to five patients with malignant pheochromocytoma. The patients received 1-3 doses of 3.33-4.625 GBq (total dose: 3.7 to 10.73 GBq). Partial tumor regression was observed in two patients, the tumor was unchanged in two patients, and slow progression was noted in one patient. Marked improvement in clinical symptoms was achieved in four patients. The other patient had no symptoms before 131I-MIBG treatment, but the serum epinephrine and dopamine decreased. There were no severe untoward responses in four patients. However, one patient developed transient but severe orthostatic hypotension, hypertension, and hyperglycemia from 1 week to 1 month after 131I-MIBG administration. Although complete remission was not obtained, all the patients achieved some benefit from 131I-MIBG therapy. Thus, 131I-MIBG appears to be useful for the palliation of malignant pheochromocytoma.

3-Iodobenzylguanidine↗
PubMed1994

CYFRA 21-1 as a tumor marker used in measuring the serum fragment of cytokeratin subunit 19 by immunoradiometric assay.

Serum levels of cytokeratin subunit 19 (CYFRA 21-1) were measured in 42 healthy volunteers, 104 cases of malignant diseases, 30 patients with chronic renal failure and 13 patients with nonmalignant and infectious diseases. The reliability of the method was demonstrated after dilution of serum samples and intra- and inter-assay reproducibility. Serum CYFRA-21-1 concentrations were less than 2.00 ng/ml in all healthy controls and 86% of the malignant cases had high serum CYFRA 21-1 levels. However slightly elevated values of CYFRA 21-1 were observed in most chronic renal failure patients. High correlation was observed between serum CYFRA 21-1 and Tissue Polypeptide Antigen (TPA) values (r = 0.90, n = 10) but not with serum alpha-feto protein (AFP) concentrations. Furthermore, cross binding tests with the CYFRA 21-1 tracer/CYFRA 21-1 antibody-coated beads and CYFRA 21-1 tracer/TPA antibody-coated beads also gave an almost linear graph. These results indicate that CYFRA 21-1 and TPA share similar type of antigens.

Biomarkers, Tumor↗
PubMed1994

Effects of oral administration of Lactobacillus casei on antitumor responses induced by tumor resection in mice.

The effects of an oral administration of BLP, a preparation of viable Lactobacillus casei YIT 9018, upon tumor growth and the mitogenic responses of splenocytes from tumor-bearing mice were studied. BALB/c mice were insufficiently pre-immunized by resecting a Colon 26 tumor mass (primary tumor) grown for 5 days intradermally. Thereafter, mice were rechallenged by injecting Colon 26 tumor (secondary tumor) into the hind footpad. The secondary tumor grew progressively in control mice, but was markedly suppressed by oral administration with BLP at a dose of 100 or 200 mg/kg/day for 7 consecutive days. The suppression was a primary tumor-specific response. Viable L. casei, not heat-killed L. casei, could suppress the secondary tumor. Although the lymphoproliferative responses of splenocytes from the secondary tumor-bearing mice with T-cell mitogens (concanavalin A and phytohaemagglutinin) and cytokines (interleukin-1 and interleukin-2) were lower than those of normal mice, this suppression of mitogenic responses under tumor-bearing conditions was abolished by oral administration with BLP. Thus we concluded that oral BLP potentiated systemic immune responses that modified T-cell functions in tumor-bearing mice.

Adjuvants, Immunologic↗
PubMed1994

Histamine release and calcium concentrations in rat mast cells are dependent on intracellular ATP: effects of prostaglandin D2.

When PGD2 (10 microM), was added to rat mast cells, it caused a rapid increase in adenosine 3',5'-cyclic monophosphate (cyclic AMP) and decrease in adenosine 5'-triphosphate (ATP), both of which recovered to their original levels within 2 min. The accumulation of cyclic AMP was maximal at 30 s after challenge with PGD2. The minimum level of ATP was observed at 30 s after addition of PGD2. The initial rise in [Ca2+]i and the histamine release induced by anti-IgE (200 micrograms/ml) were strongly inhibited at 30 s after incubation of the mast cells with PGD2. Removal of glucose from Tyrode-Hepes solution caused a rapid decrease on ATP level in mast cells, and showed strong inhibition on the rise in [Ca2+]i and histamine release induced by anti-IgE. Addition of glucose to the mast cells induced a time-dependent increase in ATP, and the rises in [Ca2+]i and histamine release were closely correlated with the recovery of ATP. These results suggested that the inhibitory mechanism of PGD2 on the initial rise in [Ca2+]i and histamine release induced by anti-IgE was due to the inhibition of ATP-dependent CA(2+)-release from the intracellular Ca(2+)-stores.

Adenosine Triphosphate↗