[A case of familial hypercholesterolemia associated with nephrotic syndrome].
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Cholestyramine Resin↗
Biomedical subjects
K Morikawa
Publications and source records attributed to K Morikawa.
Isolation of human colon carcinoma cells for resistance to a single interferon associated with cross-resistance to multiple recombinant interferons: alpha, beta, and gamma.
We established variants resistant to human interferon (IFN) from an IFN-sensitive human colon carcinoma cell line and delineated some of the mechanisms for resistance to IFN-mediated cytotoxicity. The parent KM12C cells were incubated for 2 months in medium containing recombinant human IFN-alpha hybrid BBDD (r-IFN-alpha) or recombinant human IFN-gamma (r-IFN-gamma). Surviving variants were designated KM12 alpha R and KM12 gamma R, respectively. KM12 alpha R cells were cross-resistant to the cytostatic and cytolytic effects of r-IFN-alpha, r-IFN-beta, and r-IFN-gamma, whereas KM12 gamma R cells were resistant only to the effects of r-IFN-gamma. The parent and variant cell lines had similar in vitro growth rates and similar tumorigenicity in male BALB/c nude mice, but the mechanisms for resistance to IFNs differed in the two variant lines. The resistance of the cross-resistant KM12 alpha R cell line was not attributable to the loss of specific receptors, because our analyses demonstrated the presence of receptors for IFN-gamma, whereas the KM12 gamma R line lacked specific receptors for IFN-gamma. Northern blot analyses revealed that messenger RNA (mRNA) from the proto-oncogene c-myc was equally expressed in the IFN-sensitive and IFN-resistant cell lines and that treatment with r-IFN-gamma did not alter its expression. Treatment with r-IFN-gamma induced the expression of manganous superoxide dismutase mRNA in KM12C and KM12 alpha R cells, but not in KM12 gamma R cells, confirming that both KM12C and KM12 alpha R cells, but not KM12 gamma R cells, have functional receptors for IFN-gamma.
Blotting, Northern↗
Snap helix with knob and hole: essential repeats in S. pombe nuclear protein nuc2+.
The S. pombe nuc2+ gene is required for mitotic chromosome disjunction. Its mutation arrests mitosis at the metaphase. The gene product is present in the nuclear scaffold-like fraction. The nuc2+ protein contains a domain, separated from ten 34 amino acid repeat segments, that is capable of binding AT-rich DNA in vitro. The ts mutation resides in one of the 34 amino acid repeats. Circular dichroism, limited proteolysis of the repeats, and model fitting indicate the presence of helical segments connected by protease-sensitive hinges. We propose that these repeats form a novel secondary structure (snap helix) having "knob and hole" helix-associating motifs. The packing of the snap helices would be stabilized by the bonding between the hydrophobic amino acids surrounding the knobs and holes. The nuc2+ protein may in one way bind to DNA and in another way mutually associate to form a part of the chromosome scaffold.
Amino Acid Sequence↗
Synthesis and antitumor activities of platinum complexes of unsymmetrical alicyclic diamines as carrier ligands.
The synthesis and biological activities of the platinum complexes of 2-aminomethylaziridine, 2-aminomethylazetidine, 2-aminomethylpyrrolidine, 2-aminomethylpiperidine as carrier ligands are described. The platinum complexes of 2-aminomethylazetidine and 2-aminomethylpyrrolidine are significantly effective against murine tumors. In particular, 2-aminomethylazetidine (1,1-cyclobutanedicarboxylato)platinum II (13) and 2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platin um II (16) exhibited potent antitumor activity and were soluble in water, and their antitumor activities against Colon 26 carcinoma (sc-ip system) were superior to CBDCA and comparable to CDDP.
Animals↗
Immunological regression of metastatic cancer in the liver as a result of "in vivo xenogenization".
We attempted to induce the regression of liver metastatic tumor cells in vivo by the administration to rats of Friend leukemia virus (FV) (in vivo xenogenization). The virus which was used in this experiment, FV, is highly immunogenic and does not normally cause disease in an adult rat. At first, we induced a FV viremia in tumor bearing rats in order to deliver the virus to the site of the tumor cells. FV viremia was induced by injecting 60 mg/kg cyclophosphamide (CY) i.v. after the administration of FV, and by transferring syngeneic bone marrow cells so that FV would be able to infect them and then replicate. In order that the tumor cells which were infected with virus should regress, it was necessary to break down their tolerance to FV antigens. As adoptive immunotherapy we therefore, transferred syngeneic spleen cells from rats which had been immunized with FV to tumor bearing rats. The result of this experiment was that these tumor bearing rats infected with FV which had received either normal syngeneic spleen cells or no spleen cells as controls died from liver metastasis (8 out of 9 rats (89%) and 15 out of 17 (88%) respectively). On the other hand, only 4 out of the 15 (27%) tumor bearing rats which were infected with FV and which received FV-immune spleen cells died from liver metastasis. These sets of data indicate that the in vivo xenogenization of tumor cells are indeed able to induce the regression of metastatic tumor cells.
Animals↗
A novel water-soluble dopamine-2 antagonist with anticholinesterase activity in gastrointestinal motor activity. Comparison with domperidone and neostigmine.
A novel water-soluble dopamine-2 antagonist, N-[4-[2-(dimethylamino) ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride (HSR-803) was synthesized and assayed for its gastrointestinal smooth muscle stimulating activity in vivo and in vitro. In the in vivo study, gastrointestinal contractile activity was measured by means of chronically implanted force transducers in conscious dogs; it was found that HSR-803 at 3.0 mg/kg IV probably stimulated gastric contractile force twice during the digestive state and significantly antagonized dopamine-(1.0 mg/kg per hour) inhibited gastric contractions in doses of 0.3, 1, and 3 mg/kg IV. With a background IV infusion of HSR-803 at 3 mg/kg per hour, the contraction-stimulating activity of acetylcholine (0.05 mg/kg per minute) was greatly enhanced while the response to bethanechol was not changed. As a result, HSR-803 was found to have a strong anticholinesterase activity besides the antidopamine-2 activity; i.e., the anticholinesterase activity of HSR-803 at 3 mg/kg per hour was equivalent to that of neostigmine at 10 micrograms/kg per hour, and dopamine-2 antagonistic activity of HSR-803 was similar to that of domperidone on a weight basis. No symptom suggesting actions on the central nervous system was noticed in HSR-803 up to 10 mg/kg IV in conscious dogs. In the in vitro study, HSR-803 inhibited cholinesterase dose-dependently, and IC50 was 2.9 x 10(-6) mol/L, while those of neostigmine and domperidone were 2.3 x 10(-8) mol/L and 1.7 x 10(-5) mol/L, respectively. In conclusion, HSR-803 stimulates endogenous acetylcholine release by antagonizing the dopamine-2 receptor on the postsynaptic cholinergic neurons, and the anticholinesterase activity of HSR-803 may cause the released acetylcholine to accumulate at cholinergic receptor sites. Thus, HSR-803 is potentially capable of enhancing cholinergic activity in the gastrointestinal region.
Animals↗
Indirect carotid-cavernous sinus fistula: transvenous embolization from the external jugular vein using a superior ophthalmic vein approach. A case report.
A case of indirect carotid-cavernous sinus fistula treated by combined transarterial and transvenous embolization is described. A 49-year-old woman with a right indirect carotid-cavernous sinus fistula draining solely to the right superior ophthalmic vein was treated first by transarterial embolization with polyvinyl alcohol particles. Then, by approaching through the superior ophthalmic vein from the right external jugular vein, the cavernous sinus was embolized with platinum wire using a tracker microcatheter, which resulted in marked clinical improvement. Transvenous embolization by approaching from the external jugular vein through the superior ophthalmic vein represents a promising alternative when shunted blood drains anteriorly to the superior ophthalmic vein.
Arteriovenous Fistula↗
Functional analysis of clonally expanded CD8, TCR gamma delta T cells in a patient with chronic T-gamma lymphoproliferative disease.
Leukemic cells from a patient with T-gamma lymphocytosis were found to have the surface phenotype, CD3+, CD4-, CD8+, Leu19+, TCR delta 1+, WT31-. The clonal nature of the TCR gamma delta T cell proliferation was documented by flow cytometry and Southern blot analysis. Morphologically, they were large to medium-sized mature lymphocytes with cytoplasmic granules. Functionally, the cells revealed strong cytotoxic activities against NK-sensitive target cells, but had neither killer T cell activity nor suppressive activity on PWM-driven immunoglobulin synthesis by B cells. Interestingly, both suppressive and cytotoxic T cell activities were recovered with the depletion of CD8+ T cells. These studies may suggest some functions of the CD8+ population of human TCR gamma delta T cells in a normal immune system.
Aged↗
In vitro sensitivity test of breast cancer cells to hormonal agents in a radionucleotide-incorporation assay.
Breast cancer cell lines (MCF-7, T47D, BT-20 and STT-11) and fresh cells from malignant effusions of eight breast cancer patients were examined for their in vitro sensitivity to 17 beta-estradiol (E2), tamoxifen and toremifene in a miniaturized, improved nucleic acid precursor incorporation assay (MINI assay). Seven of the eight patients received either tamoxifen or toremifene following a MINI assay and the correlation was examined between in vitro sensitivity and clinical responses to the hormonal agents. In cell lines, E2 stimulated thymidine incorporation by estrogen receptor (ER)-rich cells, MCF-7 and T47D, but not by ER-poor cells, BT-20 and STT-11. Tamoxifen induced both ER-mediated and -unmediated effects in ER-rich cells. The latter effect was also observed in ER-poor cells. Toremifene had less ER-unmediated effect in all of the cells tested than tamoxifen did. The ER-mediated effect of toremifene was weaker than that of tamoxifen in cell lines but was equipotent to tamoxifen in fresh cells. E2 affected thymidine incorporation by cells withdrawn from patients who showed a partial response to the anti-estrogens. No clear correlation was demonstrated between in vitro sensitivity to anti-estrogens of fresh cells and clinical response to these agents. The present results suggest that 1) the MINI assay is a useful system to investigate hormonal effects on breast cancer cell lines; 2) clinical responses to anti-estrogens are not predicted by in vitro response to the agents but might be predicted by the in vitro response to E2; and 3) toremifene has a smaller non-specific effect on breast cancer cells than tamoxifen and is equipotent to tamoxifen in the ER-mediated effect in vitro.
Adult↗
Correlation between the presence of microvilli and the growth or metastatic potential of tumor cells.
We used an electron microscope to examine microvilli which appear on the surfaces of various tumor cells with high or low growth potential and/or metastatic ability. The results show that a greater number of microvilli appeared on the surfaces of tumor cells (QRpP and ERpP) which possess high growth potential than on tumor cells (QR and ER) with low growth potential. We also observed that microvilli were more abundant on the surface of highly metastatic clone cells, i.e. c-SST-2 (cl-2), mouse B16 melanoma (F-10) and human colon carcinoma (KM12SM) than on weakly metastatic clone cells, c-SST-2 (cl-4-2), B16 (F-1) and (KM12C). At the same time, more microvilli were observed on the surface of B16 BL6 cells, which were obtained from the metastatic site of the B16 F10 cells, than on the surface of the parent B16 F10 cells. Immunoelectron microscopy revealed that the c-neu oncogene product, which is closely related to an epidermal growth factor receptor, was positively stained in the microvilli of tumor cells (ERpP) with high growth potential and high metastatic ability, whereas the tumor cells (ER) with low growth potential and weak metastatic ability were not stained. These findings suggest that the increased presence of microvilli correlates closely with the growth potential and metastatic ability of tumor cells.
Animals↗
Synthesis of platinum complexes of 2-aminomethylpyrrolidine derivatives for use as carrier ligands and their antitumor activities.
In order to study a new antitumor platinum complex, various platinum complexes were prepared from 2-amino-methylpyrrolidine derivatives synthesized to serve as carrier ligands and tested for their antitumor activity against Colon 26 carcinoma (s.c.-i.p. system) and P388 leukemia (i.p.-i.p. system) in mice. 2-Aminomethylpyrrolidine proved to be the most effective carrier ligand in its amine derivatives. The structure-activity relationships of the carrier ligands in the platinum complexes with dichloro, oxalato, 1,1-cyclobutanedicarboxylato and dichlorodihydroxo as leaving group were clearly shown on the Colon 26 carcinoma screen and were as follows: the antitumor activity of the platinum complexes with any leaving groups was considerably decreased by the substitution of hydrogen by alkyl group (Me, Et) on nitrogen of aminomethyl and the effects of 1,1-cyclobutanedicarboxylato Pt(II) complexes completely disappeared with the same substitution on nitrogen of pyrrolidine. In all the tested platinum complexes 2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platin um(II) (15) exhibited the most potent antitumor activity. 15 was superior to 1,1-cyclobutanedicarboxylatodiammineplatinum(II) (CBDCA) and similar to cis-diamminedichloroplatinum(II) (CDDP) on the Colon 26 carcinoma screen but it was inferior to CBDCA and CDDP on the P388 leukemia screen. Furthermore, 15 showed more potent antitumor activity than CBDCA against Colon 38 carcinoma (s.c.-i.p. system).
Animals↗
Effects of various drugs on bladder function in conscious restrained-denervated rats placed in a restraining cage and produced by transection of the hypogastric nerve.
We evaluated the effects of various intravenously administered drugs, which had been shown to influence bladder function in anesthetized and/or conscious rats, on the cystometrogram in conscious restrained-denervated rats (produced by transection of the hypogastric nerve) placed in a restraining cage in comparison to those in conscious restrained-intact rats (with the hypogastric nerve intact) placed in a restraining cage. The bladder capacity in the restrained-denervated rats was smaller than that in restrained-intact rats and did not change when they were transferred to a wide cage, but the bladder capacity of the restrained-intact rats decreased following transfer to the wide cage. Therefore, the activity of the hypogastric nerve in conscious rats appears to be stimulated by restraint. Atropine suppressed the amplitude of the micturition contraction (time to micturition in the cystometrogram). In the restrained-denervated rats, thiopental and indomethacin increased the bladder capacity at almost the same doses as those in restrained-intact rats, but it took a higher dose of morphine to increase the bladder capacity than in restrained-intact rats. These findings suggest that cystometrography in restrained-denervated rats is a useful method for evaluating the effect of a newly developed agent on bladder function without any influence from the hypogastric nerve.
Animals↗
Detrusor hyperreflexia induced by intravesical instillation of xylene in conscious rats.
Intravesical instillation of xylene (30-50%) produced detrusor hyperreflexia characterized by a decrease in both the bladder capacity (time to micturition in the cystometrogram) and the urine volume in conscious rats placed in a restraining cage. At this time, the bladder tissue showed evidence of experimental cystitis with degradation of the epithelium and edema and hemorrhage in the submucosa, and a slight increase in the content of prostaglandin E2, which stimulated directly and/or indirectly capsaicin-sensitive sensory fibers. In addition, the bladder exhibited high amplitude spontaneous activity, but the bladder contractions induced by acetylcholine, substance P, prostaglandin E2 and capsaicin were not changed following intravesical instillation of xylene. In these hyperreflexic rats, atropine suppressed the amplitude of the micturition contraction and morphine increased the bladder capacity at similar doses as in sham-treated rats, while thiopental and indomethacin increased the bladder capacity at lower doses than in sham-treated rats. These findings indicated that intravesical instillation of xylene had produced detrusor hyperreflexia in conscious rats, and that the detrusor hyperreflexia is thought to be a useful model for evaluating the effect of a newly-developed agent on bladder function.
Acetylcholine↗
Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (2nd report)--schedule of administration and clinical effects in low back pain and tooth extraction.
D-phenylalanine (DPA) is known to block the activity of carboxypeptidase, an enzyme which degrades enkephalins, endogenous morphine-like substances. Therefore, it is considered that DPA administered as an inhibiting drug of this degrading enzyme might prolong analgesia induced by acupuncture. 1) Thirty patients suffering from chronic low back pain were treated with acupuncture 30 minutes after the oral administration of 4.0 grams of DPA. The results were: excellent in 7 cases, good in 11, fair in 6 and poor in 6. Cases graded excellent and good were then compared with a placebo group. The effect was increased 26% in the DPA-acupuncture group, which shows no statistically significant difference (P less than 0.1). 2) In 56 patients, tooth extraction was performed under acupuncture anesthesia: 18 had received 4.0 gram of DPA (P.O.) 30 minutes earlier. The results were excellent in 8, good in 6, fair in 3, and poor in 1. The excellent and good cases were compared with 38 placebo group cases. The effect in the DPA-acupuncture anesthesia group was significantly increased by 35% (P less than 0.01). 3) In order to determine the optimum time for the administration of DPA, two schedules of administration were compared. [1] DPA was given on the previous day in three 0.5 gram doses (26 cases). [2] A single 4 gram dose was administered 30 minutes before treatment (30 cases). The results from the "excellent", "good" and "fair" cases showed a 16% increase in effectiveness when DPA was administered the day before, not a statistically significant difference (P less than 0.1), but a clear tendency to increase was observed. The above findings show that DPA has an enhancing effect on acupuncture analgesia and anesthesia in clinical practice.
Acupuncture Analgesia↗
[Leakage radiations in a medical electron accelerator facility--calculation of neutron doses in the facility].
Neutron doses often come dominant in mazes of electron accelerator facilities in which X-rays of energies more than 10 MV are produced. A simple analytical method to calculate neutron doses in such a facility is developed. In the calculation procedure, it is assumed that the irradiation room is spherical in shape and the maze is cylindrical. Multiple reflection of neutrons is also considered using the albedo concept in the calculation. The procedure allows to exist a hanging wall over the entrance of the irradiation room and also multiple legs in the maze. All the parameters used in the calculation are given definitely in the procedure, and any experiment is unnecessary to determine value of the parameters. Comparison of the calculated results with experimental ones will be described in the following report.
Hospital Departments↗
[Leakage radiations in a medical electron accelerator facility--measurement of neutrons and comparison with calculation].
Neutron dose equivalent rates are measured in the irradiation room and the maze of a medical electron accelerator facility. An m-counter used for measurement is associated with a gate circuit to reject piled up signals caused by pulsed X-rays, so that it is possible to measure the neutrons without obstruction by the piled up signals even in the irradiation room. Counting loss of neutrons is mathematically corrected, and the correction factor comes nearly equal to 1.5 at dose points close to the entrance to the irradiation room when 14 MV X-rays are generated. The measurement in the maze agrees with the calculation reported in the preceding report in a factor less than 1.5 except for dose points close to the entrance to the irradiation room.
Hospital Departments↗
[Leakage radiations in a medical electron accelerator facility--X-rays and capture gamma-rays].
Absorbed dose rates of photons are measured in the maze of a medical electron accelerator facility. Radiations in the maze include high energy recoiled electrons other than low energy reflected X-rays. An ionization chamber for low energy X-rays is used for measurement, and is put in a build-up cap thick enough to obstruct the recoiled electrons of which contribution to the chamber output comes sometimes equal to that of X-rays. Dose rates of capture gamma-rays in the maze are estimated applying the calculation of neutron dose equivalent rates reported in the preceding paper. It is proved that capture gamma-rays are dominant in the dose rates measured in the maze at 14 MV X-ray generation. The estimated absorbed dose rates of total photons including capture gamma-rays and reflected X-rays agree with the measured ones in the range from +10% to -27%.
Electrons↗
[Clinical psychology and polysomnographic findings on chronic insomnia in the aged].
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Age Factors↗