[Image diagnosis of renal angiomyolipoma].
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Adult↗
Biomedical subjects
K Morimoto
Publications and source records attributed to K Morimoto.
X-ray structural studies and physicochemical properties of cimetidine polymorphism.
Four crystalline forms of cimetidine, three anhydrous (forms A, B, and D) and a monohydrate (form C), obtained by slow evaporation of aqueous solutions of varying concentrations were characterized by IR spectroscopy, X-ray powder patterns, dissolution rates in deionized water, and thermal analyses. Among the three anhydrous forms of cimetidine, form A was thermodynamically more stable than the others. The structural conversion of form C into form A on dehydration was confirmed by IR spectroscopy and X-ray powder patterns. The structures of forms C and D were determined using X-ray diffraction. Form D was of spirally curled conformation; it was linked in a head-to-tail arrangement with the neighboring molecules via intermolecular hydrogen bonds between the imidazole nitrogen and guanidine nitrogen atoms. Form C was characterized by its folded conformation due to the weak stacking interaction between the imidazole and guanidine moieties; there was stabilization by double hydrogen bond formation with neighboring molecules and via water molecules of crystallization. The dissolution rate constant in deionized water for form C was approximately 1.29, 1.70, and 1.90 times greater than those measured for forms A, D, and B, respectively. There was a similar relationship among the four forms with respect to the rates of inhibition of stress ulceration. Regarding the molecular conformations of the crystalline forms and the rates of inhibition of stress ulceration, the gauche orientation of the guanidine group relative to the imidazole ring would be the conformation necessary for effective binding to the histamine H2-receptor. The compactly folded conformation of form C appears to be optimal for binding to the active site of the receptor and for clinical efficacy.
Animals↗
Proliferative kinetics and mitomycin C-induced chromosome damage in Fanconi's anemia lymphocytes.
Lymphocytes from two sisters with Fanconi's anemia (FA) were studied for cell cycle kinetics, sister chromatid exchanges (SCEs), and chromosomal aberrations when they had undergone one, two, or three or more divisions in mitomycin C (MMC)-treated cultures. Lymphocytes from the parents, another sister of the probands, and a healthy unrelated adult were examined as controls. Analyses of cell cycle kinetics by the sister chromatid differential staining method revealed that the relative frequency of metaphase cells at their third or subsequent divisions was much smaller in untreated FA cultures than in normal cultures fixed at 96 h after phytohemagglutinin stimulation. These data indicate that FA cells proliferate much more slowly than normal cells. MMC treatments of FA and normal cells led to a clearly dose-related delay in cell turnover times, the duration of delay being much longer in FA than in normal cells. FA cells had about 1.4 times higher frequencies of SCEs than normal cells in both MMC-treated and untreated cultures. FA cells also showed several times higher frequencies of chromosomal aberrations than normal cells, and the frequency of chromosomal aberrations decreased through subsequent mitoses by approximately 60% in both FA and normal cells.
Adult↗
Interaction between calcium ions and surface charge as it relates to calcium currents.
Calcium ions affect the gating of Ca currents. Surface charge is involved but to what extent is unknown. We have examined this, using isolated nerve cell bodies of Helix aspersa and the combined microelectrode-suction pipette method for voltage-clamp and internal perfusion. We found that Ba and Sr currents produced by substitution of these ions for extracellular Ca ions are activated at less positive potentials than Ca currents. Mg ions do not permeate the Ca channel and changes in [Mg]o produce shifts in the activation-potential curves that are comparable to the effects of changes in [Ba]o or [Sr]o. Inactivation of Ba currents also occurs at less positive potentials. Perfusion intracellularly with EGTA reduced inactivation of Ca currents as a function of potential, but did not shift the inactivation-potential curve. Hence, Ca current-dependent inactivation which is blocked by intracellular EGTA probably does not involve a similar change of intracellular surface potential. The voltage shifts of activation and inactivation produced by extracellular divalent cations used singly or in mixtures can be described by the Gouy-Chapman theory for the diffuse double layer with binding (Gilbert & Ehrenstein, 1969; McLaughlin, Szabo & Eisenman, 1971). From the surface potential values and the Boltzman distribution, we have computed surface concentrations that predict the following experimental observations: 1) saturation of current-concentration relationships when surface potential is changing maximally; 2) the increase in peak current when Ca ions are replaced by Sr or Ba ions; and 3) the greater inhibitory effect of Mg on IBa than ICa. Theory indicates that surface charge cannot be screened completely even at 1 M [Mg]o and thus that Ca channel properties must be evaluated in the light of surface charge effects. For example, after correction for surface charge effects the relative permeabilities of Ca, Ba and Sr ions are equivalent. In the presence of Co ions, however, Ca ions are more permeable than Ba ions suggesting a channel binding site may be involved.
Animals↗
Trihalomethanes induce sister chromatid exchanges in human lymphocytes in vitro and mouse bone marrow cells in vivo.
The four major trihalomethanes (THMs) found in chlorinated drinking water (CHCl3, CHCl2Br, CHClBr2, and CHBr3) have been investigated for their ability to induce sister chromatid exchanges (SCEs) and cell-cycle delays in human lymphocytes in vitro and to induce SCEs in mouse bone marrow cells in vivo. Each THM tested caused dose-dependent increases in SCE frequency and delays in the cell cycle. The THMs differed greatly in their ability to induce these cytological effects in vitro, with CHBr3 being the most active compound and CHCl3 the least active compound, whereas they were not markedly different in their ability to induce SCEs in vivo.
Animals↗
Proliferative kinetics of human lymphocytes in culture measured by autoradiography and sister chromatid differential staining.
A simple combination of autoradiography, to determine when a cell synthesized DNA, and sister chromatid differential staining, to determine how many times a cell has divided, was used to follow up the proliferating fate of human lymphocytes in culture. Cells were incubated continuously with 5-bromodeoxyuridine (BrdU) and pulse-labelled with 0.1 muCi/ml [3H]thymidine at various times after stimulation with phytohemagglutinin (PHA). The cells were then harvested at 4 h intervals up to 72 h, and the percentage of labelled mitoses was determined separately in first, second, or third division cells. The data showed that the cycling cells, whether they began cycling at earlier or later times after stimulation, had about the same generation times of 12--14 h. This confirms that the heterogeneity of cell generations seen in short-term lymphocyte cultures is in large part due to the difference in the times when cells began cell cycling in response to PHA.
Autoradiography↗
Induction of sister-chromatid exchanges in human lymphocytes by microsomal activation of benzene metabolites.
Metabolic activation of the benzene metabolites, catechol, hydroquinone, and phenol, by rat-liver microsomes and an NADPH-generating system (S9 mix) caused an increased induction of sister-chromatid exchanges (SCEs) in cultured human lymphocytes. There were different optimal concentrations of S9 mix for converting each benzene metabolite into further reactive forms that could induce SCE-forming lesions. The data indicate that catechol and hydroquinone can be optimally metabolized to produce reactive species, presumably benzo(semi)quinones, under conditions of lower metabolic activity than those necessary for phenol and benzene.
Benzene↗
Bilateral intracranial granulomas as a complication of infected subdural peritoneal shunt.
Intracranial granuloma in childhood is considered to be a very rare disorder. A three-year-old child is described who had bilateral intracranial granulomas originating from the ends of bilateral subdural-peritoneal shunts. Serial computerized tomographic examinations revealed variable and peculiar findings. Since subdural-peritoneal shunt is used in neonate, intracranial granuloma must be considered as a potential complication of unremoved subdural-peritoneal shunt.
Brain Diseases↗
Binding sites of calmodulin and actin on the brain spectrin, calspectin.
We used rotary-shadowing electron microscopy to map the calmodulin-and actin-binding sites on the brain spectrin, calspectin (or fodrin). Calspectin dimers appeared as rods 110 nm long and joined in a head-to-head manner to form tetramers 220 nm long. We determined calmodulin-binding sites by a ferritin-labeling method combined with biotin-avidin complex formation. Ferritin particles were found to attach to the head parts of calspectin dimers at a position 10-20 nm from the top of the head. The number of the calmodulin-binding sites seemed to be only one for each dimer and two for each tetramer. In contrast, the actin-binding sites were localized at the tail ends of the calspectin molecules. The tetramers attached to muscle F-actin with their tail ends and often cross-linked adjacent filaments. The results are discussed in view of the analogy to the erythrocyte spectrin.
Actins↗
Reaction of 1-n-propyl-1-nitrosourea with DNA in vitro.
[n-propyl-2,3-3H]1-n-Propyl-1-nitrosourea (PNU) (sp. act.: 665 mCi/mmol) was synthesized and incubated with calf thymus DNA at pH 7.0 and 37 degrees C in vitro. The degree of alkylation was proportional to the concentration of PNU added. The extent was 68 pmol/mg of DNA at 1 mM PNU. After mild acid hydrolysis, purine bases were separated by Sephadex G-10 column chromatography. Although O6-n-propylguanine and O6-iso-propylguanine were separated by this method, 7-n-propylguanine and 7-iso-propylguanine were not separated. Then we used a h.p.l.c. equipped with a mu Bondapak-C18 reverse phase column with a linear gradient elution. 7-n-Propylguanine and O6-n-propylguanine were identified as major reaction products, and 7-iso-propylguanine and O6-iso-propylguanine were identified as minor reaction products. The ratio of O6-n- and iso-propylguanine/7-n- and iso-propylguanines was 0.73. This ratio is similar to that produced by 1-ethyl-1-nitrosourea and 1-n-butyl-1-nitrosourea.
Animals↗
"Fibrinogen Tokyo II". An abnormal fibrinogen with an impaired polymerization site on the aligned DD domain of fibrin molecules.
A hereditary dysfibrinogenemia associated with defective aggregation of fibrin monomers was found in a 39-yr-old female and in the members of her immediate family, who had all been asymptomatic. The abnormality was probably due to an impaired polymerization site exposed in the DD domain of two adjacent fibrin molecules, because plasmic fragment DD derived from the propositus' cross-linked fibrin bound far less tightly to insolubilized normal fragment E than that from the normal one. Its complementary polymerization site in the E domain of fibrin, which was exposed by thrombin cleavage, and the polymerization site in the D domain of fibrinogen, which was available without activation by thrombin, were both found to be normal. More anodal migration of the abnormal fragment DD than the normal one, as shown by immunoelectrophoresis, seemed to support our concept that the mutation most likely resides in the D domain of the abnormal fibrinogen molecule at or near a region closely related to the polymerization site that is exposed when two fibrin molecules are linearly aligned. The work of others on the polymerization of normal fibrin with different techniques yielded results consistent with our conclusions. We tentatively designate this type of abnormal fibrinogen "fibrinogen Tokyo II," but its possible identity with other abnormalities of fibrinogen reported heretofore is not excluded.
Adult↗
Enhancement of lymphatic transport of 1-(2-tetrahydrofuryl)-5-fluorouracil by polyacrylic acid aqueous gel and emulsion type suppositories in rats.
1-(2-Tetrahydrofuryl)-5-fluorouracil (FT-207) concentrations in lymph and plasma were measured after rectal administration of three types of suppositories containing FT-207. The suppositories used in this study were prepared from polyacrylic acid aqueous gel bases, emulsion type bases and a commercial fat base, witepsol w-35. Both aqueous gel and emulsion type suppositories were superior to the suppositories from witepsol with regard to FT-207 concentration in lymph and plasma. The addition of aqueous gel to the polyacrylic acid aqueous gel was found to be effective for the lymph transport from the aqueous gels. Polyacrylic acid aqueous gel containing 1% glycyrrhizin was better than other suppositories. Solidification of the emulsion type bases are also investigated, and it is suggested that these may be better substitutes of the oily suppository.
Acrylic Resins↗
Studies on the molecular weight of active and inactive renins in essential hypertension.
The molecular weight (MW) of active renin (AR) and inactive renin (IR) was investigated in individual plasma samples from 15 essential hypertensive and 5 normal subjects. The patients with essential hypertension were classified into 3 subgroups: low plasma renin activity (PRA), normal PRA and high PRA. The MW of AR and IR was estimated by Sephadex G-100 gel filtration. IR in the eluates was activated with trypsin. Plasma renin activity and renin activity in eluates were measured by radioimmunoassay of angiotensin I. At least 3 sizes of AR (MW: 48,000, 53,000 and 57,000) and 2 sizes of IR (MW: 53,000 and 57,000) were discovered, and the MW of AR was less than or equal to the MW of IR. The larger AR was predominant in the low PRA group and the smaller one in the high PRA group. This was also true for IR. This relation was also observed in the 2 types (high renin and low renin) of pooled plasma. In high renin pooled plasma the MW of AR and IR was about 48,000 and 54,000, respectively, while both were about 56,000 in low renin pooled plasma. It appears that the larger type of AR and IR remains in the circulation in the suppressed renin state, and that the smaller type of renins enters into the circulation when the secretion of renins is enhanced.
Enzyme Precursors↗
Anti-epileptic effects of TRH-T and DN-1417.
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Amygdala↗
Specific cleavage of calmodulin-binding proteins by low Ca2+-requiring form of Ca2+-activated neutral protease in human platelets.
Occurrence of Ca2+-dependent calmodulin-binding proteins in lysed human platelets and their cleavage by low Ca2+-requiring Ca2+-activated protease were investigated by a gel overlay technique using [125I]calmodulin. Calmodulin-binding polypeptides of Mr 100K, 90K, 60K, and 40K were detected in lysed platelets, of which 90K and 60K polypeptides were rapidly degraded to lower molecular weight products in the presence of micromolar concentrations of Ca2+. Then, we investigated cleavage of calmodulin-binding proteins by purified low Ca2+-requiring Ca2+-activated neutral protease from human platelets. As substrate, myosin light chain kinase and caldesmon purified from the chicken gizzard smooth muscle were used. In the presence of micromolar concentration of Ca2+, these two proteins were also rapidly degraded to lower molecular weight species, which were still capable of binding to calmodulin.
Animals↗
[Anticonvulsant effect of a novel TRH analog (DN-1417) on amygdaloid kindled seizure].
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Amygdala↗
[Anticonvulsant effect of a novel TRH analog (DN-1417) on amygdaloid kindled seizure II; comparison with TRH tytrate].
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Amygdala↗
[Anticonvulsant effects of TRH analog. 3. Prophylactive effects of DN-1417 on kindling model].
We reported previously that TRH . T and a novel TRH analog, DN-1417 had anticonvulsant effects in kindling cat preparations which had been established as an experimental model of epilepsy. Although acute anticonvulsant effect of DN-1417 was short-lasting without dose-related efficacy, DN-1417 administration resulted a lasting increase in convulsive threshold in some cases. In order to study the effects of DN-1417 on kindling seizure development (prophylactic effect), 10 amygdaloid kindling cats were examined. The animals in the DN-1417 group (N = 4) were treated with the agent (1 mg/kg) prior to each daily kindling stimulation for 35 days (drug sessions). Six cats in control group were kindled without drug treatment. Kindling rates, changes in after-discharge duration, and positivity of transference phenomenon to contralateral amygdala were compared between these two groups. The results obtained were: 1) Positive prophylactic effects on kindling was found in 3 cats of DN-1417 group. In these cats, 19 (7-37) additional daily stimulation to those given during the drug session were required for the kindling. 2) No positive transfer to contralateral amygdala was found in 2 of 3 cats of DN-1417 group. 3) During the drug sessions, self-sustained afterdischarges were fragmented into separated bursts of discharges with short duration in 2 cats of DN-1417 group. These results suggested that DN-1417 may prevent a trans-synaptic change underlying the kindling, which might relate to the long-lasting anticonvulsant effect reported clinically. A possible mechanism underlying the prophylactic effects of DN-1417 was discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗