Biomedical subjects
Publications and source records attributed to H Enomoto.
An 8-month-old dog with a history of gastrointestinal disturbances and neurological signs was presented with hyperammonemia. Necropsy revealed ascites, portosystemic collaterals, and an irregularly surfaced small liver. Histologically, there were diffuse neuronal necrosis and focal spongiform changes in the brain, and marked fibrosis in the liver. Hepatic encephalopathy was diagnosed.
Vitamin D-dependent calcium-binding protein (calbindin-D28K), is regulated by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and several other factors in a tissue-specific manner, but the controlling mechanisms are still poorly understood. In this study we examined the relative contributions of transcriptional and posttranscriptional mechanisms in the 1,25-(OH)2D3 control of calbindin-D28K mRNA expression in primary chick kidney cells and investigated the effect of extracellular Ca2+ on calbindin-D28K gene expression in the presence and absence of hormone. 1,25-(OH)2D3 treatment (10(-8) M) of cells grown in serum-free medium resulted in a marked 20- to 30-fold increase in calbindin-D28K mRNA peaking at 12-18 h, which then rapidly declined to basal levels by 24 h. The abrupt decline in mRNA appeared to be associated with a reduction in size of the calbindin-D28K transcripts. Nuclear run-off assays showed only a slight (1.5-fold) increase in calbindin-D28K gene transcription 2 h after 1,25-(OH)2D3, whereas parallel assays clearly demonstrated a marked (7-fold) induction in the rate of metallothionein gene transcription 2 h after treatment of chick kidney cells with 10 microM zinc. The induction of calbindin-D mRNA by 1,25-(OH)2D3 required ongoing protein synthesis, since it was blocked by cycloheximide. Calbindin-D28K mRNA was stable for 12 h in the presence of actinomycin-D in both vitamin D-deficient and 1,25-(OH)2D3-treated cells. Both basal and 1,25-(OH)2D3-induced calbindin-D28K mRNA were modulated by the extracellular Ca2+, with maximum expression occurring at 1-2 mM. We conclude that 1,25-(OH)2D3 induces kidney calbindin-D28K mRNA by producing a small increase in its transcriptional rate, which is accompanied by pronounced posttranscriptional effects(s). The striking modulation of calbindin-D28K expression by extracellular Ca2+ is consistent with a putative role for this protein in the regulation of this ion in the kidney cell.
Selective and potent HIV protease inhibitors containing allophenylnorstatine [Apns; (2S, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid] as a transition-state mimic were designed and synthesized. Among them, conformationally constrained tripeptide derivatives, kynostatin (KNI)-227 and -272 (Fig. 1), exhibited highly potent antiviral activities against a wide spectrum of HIV isolates. Ready availability due to the simple synthetic procedure and the excellent antiviral properties indicate that KNI-227 and KNI-272 are promising candidates as selective anti-AIDS drugs.
The expression and induction of heat shock proteins (HSPs) were examined in cultured SV-40-transformed human retinal pigment epithelial (RPE)-derived cells following exposure to chemical oxidants. Concentrations of hydrogen peroxide and the organic oxidants tert-butyl hydroperoxide, cumene hydroperoxide and linoleic acid hydroperoxide were used under conditions where cell viability was between 75% and 90% as determined by the trypan blue exclusion tests. The types of HSPs that are either induced and/or elevated from constitutive levels in cultured transformed cells were separated both by SDS-PAGE and by two-dimensional gel electrophoresis. Subsequent immunoblotting was performed with both a monoclonal antibody (MAb C92) specific for only the stress-inducible form of HSP 70, namely HSP 72, and with a monoclonal antibody (MAb N27) specific for both the stress-inducible HSP 72 and its constitutive form, HSP 73. As positive controls for comparison, other types of stressing agents were used that included heat shock at 41 degrees C for various times and exposure to the proline analogue, azetidine-2-carboxylic acid (AzC). Protein immunoblotting analysis demonstrate that: (a) Stress-inducible HSP 72 is present at low levels in non-stressed cultured transformed RPE-derived cells and in fresh bovine retina and RPE, but is not detectable in non-stressed cultured lung fibroblasts until induction with heat shock; and (b) Stress-inducible HSP 72 is elevated from constitutive levels in RPE-derived cultured cells after exposure to various oxidants. After cellular exposure to both organic oxidants and to AzC in the presence of L-[35-S]-methionine, two-dimensional gel electrophoresis confirmed the elevation of newly synthesized HSP 72. Thus, these results indicate that cultured human SV-40-transformed RPE-derived cells are capable of elevated HSP 72 biosynthesis under conditions of oxidative stress produced by organic oxidants.
This study examined the relationship between self-disclosure and loneliness. The self-disclosure questionnaire (ESDQ) and the loneliness scale (LSO, consists of two subscales, U-scale and E-scale) were administered to 114 female subjects (junior college students). Results show that self-disclosure scores were negatively related to the U-scale of loneliness (whether or not they believe in mutual sympathy among human beings), but not to the E-scale of loneliness (whether or not they are conscious of individuality of each individual). The results suggest that we have to specify the quality of loneliness in question, when we examine the relationship between self-disclosure and loneliness.
Beta-2-microglobulin (beta 2-MG) is a well-known tumor marker, particularly in patients with multiple myeloma (MM) in whom survival decrease in relation to high serum beta 2-MG concentrations. We investigated the level of serum beta 2-MG by radioimmunoassay (RIA) double antibody method in 14 cases of MM, 13 cases of benign monoclonal gammopathy, and 25 healthy controls. Beta-2-MG of the kidneys was stained by the MM by peroxidase-anti-peroxidase (PAP) method and clinical courses were compared. In controls, the serum beta 2-MG concentration increased with aging, and its concentration of MM was higher than that of controls. Most MM patients with positive beta 2-MG staining in glomeruli showed poor prognosis. Beta-2-MG staining of proximal and distal tubuli did not contribute to the prognosis of MM.
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The authors present a rare case in which a choroid plexus papilloma originating in the left cerebellopontine angle region metastasized and formed a space-occupying lesion in the right temporal region. A 46-year-old woman with choked disks presented with two separate mass lesions in the right temporal and the left cerebellopontine angle regions. Magnetic resonance imaging exhibited the relationship between the tumors and the surrounding structures. To our knowledge, no case has been reported in which a choroid plexus papilloma originating in the cerebellopontine angle region formed a space-occupying lesion in the right temporal region.
A 42-year-old female with high fever and headache was admitted. Physical examination revealed hypertension, thrombocytosis with megakaryocytosis, hyperfibrinogenemia, and high level of serum noradrenaline. After operation of extramedullary pheochromocytoma, all symptoms disappeared and findings became normal. The supernatant of tumor culture showed high levels of interleukin-6.
Parathyroid hormone-related protein (PTHrP), which is responsible for producing hypercalcemia in patients with humoral hypercalcemia of malignancy, has recently been identified in several normal tissues. Because PTHrP, like parathyroid hormone (PTH), is known to exhibit vasodilatory properties, we investigated the expression and regulation of PTHrP mRNA in cultured rat aortic smooth muscle cells (SMC). We report here that PTHrP mRNA is expressed in SMC and is markedly induced by serum in a time- and concentration-dependent fashion. Addition of 10% fetal calf serum to serum-deprived, confluent cells, resulted in a marked induction of PTHrP mRNA by 2 h with a peak at 4-6 h. PTHrP was detected in SMC by immunocytochemistry and radioimmunoassay of conditioned medium, and was shown to be up-regulated within 24 h after the addition of serum. The serum induction of PTHrP mRNA was blocked by actinomycin D and by cycloheximide indicating the need for protein synthesis to evoke the serum effect on PTHrP gene transcription. In addition, treatment with dexamethasone, which has been previously shown to reduce the constitutive expression of PTHrP in human cancer cells, also blunted the serum induction of PTHrP mRNA in SMC. Treatment of quiescent cells with the serum mitogens platelet-derived growth factor or insulin-like growth factor-I had no effect on PTHrP, whereas the vasoactive peptides endothelin, norepinephrine and thrombin stimulated PTHrP expression. Exogenous addition of recombinant PTHrP-(1-141) had no significant effect on SMC DNA synthesis as measured by [3H]thymidine incorporation. In summary, the abundance of PTHrP mRNA and the characteristics of its regulation in SMC suggest a major role for PTHrP as a local modulator in vascular smooth muscle.
A series of N-phenyl-delta 8-dihydroabietamide analogs were prepared and tested for hypocholesterolemic activity. The effects of substituents of the phenyl moiety on the activities were quantitatively analyzed by using various substituent parameters. The activities were enhanced by the electron-donating effect of ortho and para substitutents and the bulkiness of ortho substituents. A combination of 2,6-dimethylaniline with resin acids other than delta 8-dihydroabietic acid produced lower activities than N-(2,6-dimethylphenyl)-delta 8-dihydroabietamide, abietane-type carboxamides being somewhat stronger than pimarane-type carboxamides. The conversion of the carboxamide group to other groups resulted in more or less of a decrease in activity, giving evidence that the carboxamide group is important to hypocholesterolemic activity.
A device to irradiate a monolayer of cultured cells with alpha-particles using an Am-241 alpha-source (33.4 MBq) was designed to investigate RBEs of alpha-particles in cell killing, induction of chromosome aberration, mutagenic changes and transformation. This device can be used conveniently in a common laboratory by a small number of researchers without any limitation of machine time. The device performs as follows: (1) The energy of alpha-particles at the entrance of the cell layer is 3.20 MeV with a standard deviation of 0.25 MeV, (2) the incident angle to the cell layer is 82.8 degrees with a standard deviation of 3.2 degrees, (3) the fluence rate is 4.7 x 10(5) cm-2.min-1, (4) the average LET infinity for a cell layer 5 microns thick is 138 keV/micron, (5) the average dose rate for a cell layer 5 microns thick is 0.10 Gy/min., (6) a temperature and CO2 concentration conducive to cell cultivation are maintained during irradiation.
A 64 years old woman with anterior chest wall recurrence after bilateral mastectomy for breast cancer was treated by the resection of chest wall in full thickness involving the whole sternum and the anterior part of ribs except the first rib. The thoracic cage was reconstructed using a free rectus abdominis myocutaneous flap which was placed over Marlex mesh covering the defect of chest wall. By means of surgical microscope, inferior epigastric artery and vein of the graft were anastomosed with internal thoracic artery and vein at the neck, respectively. Postoperative course was uneventful and the patient is alive and well for one year after the surgery. A free myocutaneous flap method provides enough volume of soft tissue for coverage of a large defect and chest wall stability.
It has been reported that mental retardation due to congenital hypothyroidism can be prevented by early detection and early adequate replacement therapy. We have developed a radioimmunoassay for TSH using the dried blood spot and have started screening for newborn congenital hypothyroidism using a part of sample of the inborn metabolic error screening. (1) The dried blood spot TSH of 61,000 newborn infants was assayed in the first half of our screening and that of 74,505 newborn infants was assayed in the latter half of our screening. As a result, although we were not able to detect any cases in the first screening, we were able to detect 9 cases of congenital hypothyroidism in the latter screening. From the results obtained through our investigation of the thyroid function of these 9 infants, we confirmed that mild hypothyroidism can be better detected by the screening of TSH. (2) As to the program of the screening, we chose from the latter half of our screening all the samples in which TSH concentrations contained above 3 percent of each assay and were remeasured on the next assay. (3) As we confirmed that the sensitivity of measurement was increased at very low concentrations, when the volume of antibodies, radioisotopes and eluates used for each assay were decreased, we measured TSH successfully using two 3 mm discs. (4) As we can perform very simple screening by the 3 mm disc method, we are changing the screening method from that with 10 mm disc to one with two 3 mm discs. We intend to extend our screening, and will make every effort to prevent mental retardation due to congenital hypothyroidism.
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Explore the source record for details and available documents.