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Biomedical subjects

T Tada

Publications and source records attributed to T Tada.

At least 235 records · Page 13Linked to original sources

Radiosensitizing, toxicological, and pharmacokinetic properties of hydroxamate analogues of nitroimidazoles as bifunctional radiosensitizers/chemical modifiers.

We examined the pharmacokinetics of KIH-802, potassium 2-nitroimidazole-1-acetohydroxamate, using its radioisotope-labelled compound and the acute toxicity in mice. We discovered that the concentration of KIH-802 was very low in the brain and its LD50 was nearly half the value of that of MISO. We also present here new 2-nitroimidazole radiosensitizers/chemical modifiers (KIN-804, 811, 831, 841, 844, 821, 823 and 824) designed to enhance their sensitizing ability intensely by substituting various biologically active groups, such as hydroxamic acids and oximes, with moderate lipophilicity to the aromatic ring, if necessary, through some spacers. The sensitizing effects of all compounds were estimated to be almost equal to or better than that of MISO. The results of their toxicities shows that new hydroxamates KIN-804 and 831 are less toxic than KIH-802 and MISO. Their in vitro enhancement ratios are 2.00 and 1.75, respectively, compared with those of KIH-802, MISO and SR-2508, 1.77, 1.72 and 1.72, respectively, at each dose of 1 mM for EMT6/KU single cell. We concluded that they may be superior radiosensitizers of hydroxamic acid analogues to KIH-802.

Animals↗

Kinetic study of the transformation from tetrahydrate to monohydrate of a new antiallergic, sodium 5-(4-oxo-phenoxy-4H-quinolizine-3-carboxamide)-tetrazolate.

Two hydrates (tetrahydrate, I, and monohydrate, II) of a new antiallergic, sodium 5-(4-oxo-phenoxy-4H-quinolizine-3-carboxamide)-tetrazolate (FR71021), were prepared and characterized by means of infrared spectrometry, thermal analysis, and power X-ray diffraction spectrometry. While I was confirmed to dehydrate readily resulting in an anhydrate form (noncrystalline form) below its critical relative humidity for dehydration, I was also transformed into II under humid conditions. The transformation kinetics from I to II were investigated under varying temperature and humidity conditions by a powder X-ray diffraction technique. The transformation mechanism followed a zero-order reaction, and the apparent transformation rate constant (k) could be described as a function of water vapor pressure (P), temperature (T), and the interaction orders between water vapor pressure and the samples (s): k = A.exp(-Ea/RT).Ps, where Ea is the activation energy and R is the gas constant.

Biotransformation↗

Intracranial mycotic aneurysm caused by Aspergillus--case report.

A 75-year-old female with chronic renal failure diagnosed as Wegener's granulomatosis was receiving steroids and immunosuppressive agents when subarachnoid hemorrhage developed. Cerebral angiography showed a fusiform aneurysm arising from an angular branch of the left middle cerebral artery. Hemorrhage occurred and the aneurysm was excised by emergency surgery. Microscopic examination of the aneurysm revealed dense infiltration of hyphae identified as Aspergillus. She died of subsequent hemorrhage. Autopsy showed numerous Aspergillus hyphae in the lung. Fungal mycotic aneurysm should be considered in the differential diagnosis of an immunocompromised patient with subarachnoid hemorrhage.

Aged↗

WF11605, an antagonist of leukotriene B4 produced by a fungus. II. Structure determination.

The structure of WF11605, a novel tetracyclic triterpene glucoside, was determined to be 1. The plane structure of deacetyl-WF11605 aglycone was elucidated as 2 through the concerted application of a series of 2D NMR techniques. The relative configurations were established by X-ray crystallographic analysis of bis(p-bromobenzoyl) derivative 3 and absolute stereochemistry by CD exciton chirality method.

Chrysenes↗

[Changes in seizure-triggering threshold and after discharge duration in seizure susceptibility].

Epilepsy is analysed on terms of two different conditions, seizure susceptibility and seizure induction. Reports on detailed changes of seizure-triggering threshold and after discharge duration in seizure susceptibility are few. We examined staged changes of seizure-triggering threshold and after discharge duration in seizure susceptibility in a cat amygdaloid kindling model. Ten crossed adult cats were used. We investigated after discharge threshold (ADT), partial seizure threshold (PST) in stage 4 group (P) and generalized seizure threshold (GST) in stage 6 group (C). At the same time, we examined after discharge duration on electroencephalograph (EEG) in each stage. Seizure-triggering threshold decreases significantly step by step. After discharge duration increases significantly step by step. It is concluded that staged decrease of seizure-triggering threshold and increase of seizure's grade and duration was seen in seizure susceptibility.

Amygdala↗

Suppression of immune responses by cloned T cells and their products.

We have established a number of IL-2 dependent T cell clones with a definite suppressor function for the antibody response. Our collection included CD4+ helper (Th) and suppressor T cell (CD4+ Ts), and CD8+ cytotoxic (Tc) and suppressor T cell (CD8+ Ts) clones. Ts clones were defined by their suppressive activity on antigen-induced proliferative response and on helper functions of other CD4+ Th clones without detectable cytotoxicity and production of known helper type interleukins. The I-J expression was found to be present on both Th and Ts clones, and was generally associated with the H-2 restriction specificity of TcR of these clones. We have shown that the activated CD4+ Ts cells could inhibit the increase of intracellular Ca2+ of Th clones induced by antigen-pulsed antigen-presenting cells (APC). The identity of MHC restriction-specificities was required for the instant suppression of Ca2+ influx of Th clones, while a longer period of activation of Ts clones was needed to suppress the response of Th clones having different MHC restrictions. A strict selectivity was found in the suppressive activity of Ts clones in that Ts clones could suppress the Ca2+ responses of Th1 or Th2 clones but not of other CD4+ Ts clones. Ts clones could suppress the Ca2+ influx of Th clones induced only by antigen-pulsed APC or anti-TcR antibody but not by Con A or IL-2. Both CD4+ and CD8+ Ts clones released soluble immunosuppressive factors upon stimulation with immobilized anti-CD3 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Postoperative intracranial hemorrhage due to vitamin K deficiency: report of two cases].

Vitamin K deficient hemorrhagic diathesis is well known as a cause of infantile intracranial hemorrhage. Its occurrence, however, as a post-surgical complication is rare and has never been reported previously. Two cases are presented here which illustrate the existence of such a hazard. Case 1. A 73-year-old woman admitted with subarachnoid hemorrhage (WFNS IV) underwent microsurgical exploration of a left internal carotid aneurysm, and neck clipping of the aneurysm was performed. She had an uneventful postoperative course, but her neurological condition deteriorated suddenly on the fifth postoperative day. CT scan revealed a large epidural hematoma. Case 2. A 6-year-old boy was admitted due to the dysfunction of a ventriculo-peritoneal shunt system that had previously been placed for hydrocephalus. This dysfunction was thought to be caused by meningitis. Twelve days after ventricular drainage and antibiotic therapy, sudden intraventricular hemorrhage occurred. In both cases, PT and APTT were markedly prolonged, FDP slightly increased and fibrinogen slightly decreased. SFMC was positive in case 2. After the administration of vitamin K, PT and APTT were immediately normalized. Recent reports emphasize the adverse effect of antibiotics that leads to vitamin K deficient hemorrhagic diathesis, especially, in patients in a cachectic state. In these two cases, such a cachectic condition was not observed. We presume that the cause of vitamin K deficiency would be, along with the administration of antibiotics, a preliminary condition of disseminated intravascular coagulation which is encountered in some neurological disorders including subarachnoid hemorrhage. We conclude that attention should be paid for these pitfalls in perioperative neurosurgical care.

Aged↗

Molecular events in the T cell-mediated suppression of the immune response.

To understand the mechanism of T cell-mediated suppression, we have established a number of suppressor T cell (Ts) clones of both CD4+ and CD8+ phenotypes that exert a definite suppressive effect on antigen-induced proliferative response of normal and cloned CD4+ helper T cells (Th). When an antigen-activated Ts clone was added to Th clones that were subsequently stimulated with antigen and APC, the increase of intracellular Ca2+ in the latter was greatly inhibited. The suppression was unidirectional where Ts suppressed Th but not vice versa. A Ts clone could not suppress other Ts clones. Exactly the same suppression of Ca2+ response could be induced by the treatment of T cells with an anti-I-J antibody. The anti-I-J suppressed the Ca2+ response of Th clones induced by antigen-pulsed APC and anti-TcR alpha beta antibody, whereas the responses to anti-CD3 and Con A were not inhibited. The difference in the effect of anti-TcR alpha beta and anti-CD3 suggests that the suppression is caused by a functional uncoupling of TcR alpha beta and CD3. The stimulation of Ts clones with anti-CD3, on the other hand, induced a unique suppressor factor that potently inhibits the antigen- and anti-TcR induced proliferation of CD4+ Th clones.

Animals↗

Cloning and nucleotide sequence of a human Zn-alpha 2-glycoprotein cDNA and chromosomal assignment of its gene.

A cDNA clone of Zn-alpha 2-glycoprotein (Zn alpha 2gp) was isolated from a human prostate library. The amino acid sequence of prostate Zn alpha 2gp deduced from the nucleotide sequence was identical to the one previously reported on the Zn alpha 2gp protein purified from human blood plasma, except at three positions: the 65th and 222nd amino acid residues were Gln (----Glu) and Glu (----Gln), and there was a two amino acid insertion (Ile-Phe) between the 75th (Glu) and 76th (Met) amino acids. Southern blot analysis of human genomic DNA, however, suggested a single gene encoding Zn alpha 2gp. Using a panel of rodent-human somatic cell hybrids, the Zn alpha 2 gp gene was assigned to human chromosome 7.

Amino Acid Sequence↗

Congenital angiotropic lymphoma (intravascular lymphomatosis) of the T-cell type.

The autopsy of a stillborn infant showed an extensive intravascular proliferation of atypical cells throughout the body. There was no infiltration by these cells of the parenchyma of the bone marrow, lymph nodes, or thymus. By histochemistry, these cells were negative for naphthol-ASD-chloroacetate esterase, a marker of granulocytes. By immunohistochemistry, they were reactive with MT-1 and anti-Leu-22, but unreactive with MB-1, L26, anti-Leu-M1, Tü-9, and antihemoglobin antibodies. A few cells reacted with antileukocyte common antigen and UCHL-1. Based on these findings, the lesion was diagnosed as angiotropic lymphoma (intravascular lymphomatosis) of the T-cell type, which occurred congenitally. Most angiotropic lymphomas in the literature are of the B-cell type, and no leukemia virus type I antibody was negative in the mother.

Female↗

Transforming growth factor-beta-induced inhibition of T cell function. Susceptibility difference in T cells of various phenotypes and functions and its relevance to immunosuppression in the tumor-bearing state.

The present study investigates the nature of humoral component(s) generated in tumor-bearing hosts to induce immune dysfunction of T cells. Cell-free ascitic fluid and culture supernatant (SN) were obtained from the ascites and cultures allowing MH134 hepatoma cells to grow. These ascites and SN samples were tested for their abilities to influence the generation of CTL responses to TNP and alloantigens. The generation of the anti-TNP CTL responses that require self H-2-restricted CD4+ Th cells was markedly suppressed by addition of the ascites or SN under conditions in which these samples did not inhibit anti-allo CTL responses capable of using alternate pathways of allo-restricted CD4+ and CD8+ Th. The activation of CD8+ CTL precursors and CTL activity were also resistant to the ascites or SN. The ascites- or SN-induced suppressive effect to which CD4+ Th were most susceptible was found to be mediated by transforming growth factor-beta (TGF-beta) activity, because: 1) the TGF-beta activity was detected in the MH134 ascites and culture SN; 2) the suppression of CD4+ Th function required for anti-TNP CTL responses was almost completely prevented by addition of anti-TGF-beta antibody to cultures and; 3) rTGF-beta also induced similar patterns of immunosuppression to those observed by ascites or SN. These results indicate that TGF-beta produced by tumor cells induces deleterious effects on T cell, especially on the CD4+ Th subset, and provide an explanation for the molecular mechanism underlying the previously observed CD4+ Th-selective suppression in the tumor-bearing state.

Animals↗

Effects of sublingual nitroglycerin in patients receiving transdermal nitroglycerin for coronary artery disease: prevention of cross-tolerance.

The systemic hemodynamic and coronary dilative responses to sublingual nitroglycerin were studied in patients receiving transdermal nitroglycerin. A total of 48 patients with coronary artery disease were divided into 4 groups: 12 patients receiving 1 tablet of sublingual nitroglycerin without transdermal nitroglycerin (Group 1), 12 patients receiving 1 tablet of sublingual nitroglycerin with 12-hour-daily intermittent therapy of transdermal nitroglycerin (Group 2), 12 patients receiving 1 tablet of sublingual nitroglycerin with continuous therapy of transdermal nitroglycerin with continuous therapy of transdermal nitroglycerin (Group 3), and 12 patients receiving 2 tablets of sublingual nitroglycerin with continuous therapy of transdermal nitroglycerin (Group 4). Before and during administration of sublingual nitroglycerin, aortic pressure, left ventricular pressure, and coronary artery diameter were examined at diagnostic cardiac catheterization in all patients. During sublingual nitroglycerin, the decreases of aortic systolic pressure and left ventricular end-diastolic pressure were greater in Group 1, 2, and 4 than in Group 3. Dilation of coronary arteries by sublingual nitroglycerin tended to be greater in Group 1, 2, and 4 than in Group 3. Thus, the effects of sublingual nitroglycerin for the relief of ischemia might be more prominent in patients with intermittent therapy of transdermal nitroglycerin than in those with continuous therapy. The increased dose of sublingual nitroglycerin for the relief of ischemia might be more effective in patients with continuous therapy of transdermal nitroglycerin.

Administration, Cutaneous↗

X-ray structural studies and physicochemical characterization of (E)-6-(3,4-dimethoxyphenyl)-1-ethyl-4-mesitylimino-3-methyl- 3,4-dihydro-2(1H)-pyrimidinone polymorphs.

The polymorphism of (E)-6-(3,4-dimethoxyphenyl)-1-ethyl-4-mesitylimino-3-methyl-3,4-di hydro- 2(1 H)-pyrimidinone (FK664; 1) was characterized by using X-ray powder diffractometry, differential scanning calorimetry (DSC), and IR spectroscopy. Structures of two polymorphs (Forms A and B) were determined by X-ray crystallographic analysis. Form A crystallized in the monoclinic space group P2(1)/c, with a = 13.504(2), b = 6.733(1), c = 24.910(8) A, beta = 96.55(4) degrees, z = 4, and dcal = 1.203 g/cm3, while Form B crystallized in the same space group, with a = 8.067(2), b = 15.128(4), c = 18.657(4) A, beta = 102.34(3) degrees, z = 4, and dcal = 1.216 g/cm3. The conformational features of 1 were very similar between the two polymorphs. Compound 1, in both crystal forms, took an energetically reasonable conformation in three rigid planes, such as 2-pyrimidone, trimethylphenyl, and dimethoxyphenyl rings, but the molecules were packed in different ways between the two polymorphs. In the Form B crystal, a short contact was possible, to form pi-pi interactions between two dimethoxyphenyl groups related with the inversion center in the crystal lattice; this interaction seems to contribute to stabilizing the crystal structure of Form B. Both Forms A and B showed only one endothermic peak due to fusion at 115 and 140 degrees C, respectively, on the DSC thermograms; therefore, it is suggested that there are no transition points between the two polymorphs. The heats of fusion obtained from the DSC thermograms were 33.2(2) kJ/mol for Form A and 36.8(1) kJ/mol for Form B.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗

Intracerebral hemorrhage in carotid-cavernous fistula.

This report describes a case of traumatic carotid-carvernous fistula which presented as an intracerebral hemorrhage. The usual ocular signs were absent due to an atypical drainage pattern from the cavernous sinus. Engorgement of the deep venous system of the brain due to the carotid-cavernous fistula was thought to have caused the intracerebral hemorrhage.

Arteriovenous Fistula↗

Effects of digoxin, propranolol, and verapamil on exercise in patients with chronic isolated atrial fibrillation.

STUDY OBJECTIVE: The aim was to evaluate the effects of digoxin, propranolol, and verapamil on exercise in patients with chronic isolated atrial fibrillation. DESIGN: Patients with chronic isolated atrial fibrillation underwent maximal exercise testing before and after the administration of digoxin, propranolol, or verapamil. Heart rate, oxygen uptake and oxygen pulse were observed at rest, at gas exchange anaerobic threshold, and at peak exercise. SUBJECTS: The subjects were 10 patients (aged 48-78 years, mean age 60, SD 9, years) with chronic isolated atrial fibrillation. MEASUREMENTS AND MAIN RESULTS: During exercise without medication, the heart rate was 85 (SD 8) beats.min-1 at rest, 127(19) at the level of anaerobic threshold, and 175(17) at peak exercise. With digoxin, heart rate was reduced to 75(9) beats.min-1 at rest (control v digoxin, p less than 0.01). However, reduction of heart rate was not seen at anaerobic threshold or at peak exercise. With propranolol, heart rate was 63(7) beats.min-1 at rest, 99(16) at anaerobic threshold, and 138(28) at peak exercise (control v propranolol, all p less than 0.01). Heart rate with verapamil was 70(13) beats.min-1 at rest, 107(30) at anaerobic threshold, and 138(28) at peak exercise (control v verapamil, p less than 0.05 at rest and at anaerobic threshold, p less than 0.01 at peak exercise. Neither digoxin, nor propranolol, nor verapamil changed the oxygen uptake during exercise. Without medication, oxygen pulse was 6.5(2.0) ml.beat-1 at anaerobic threshold and 7.7(2.1) ml.beat-1 at peak exercise. With digoxin, the change of oxygen pulse, versus without medication, was not significant at rest or at anaerobic threshold but was increased at peak exercise, at 8.3(2.1) v 7.7(2.1) ml.beat-1, p less than 0.05. With propranolol, oxygen pulse was increased to 8.2(1.9) ml.beat-1 at anaerobic threshold and 9.2(2.3) ml.beat-1 at peak exercise (control v propranolol, both p less than 0.01). With verapamil, oxygen pulse was increased to 8.7(1.8) ml.beat-1 at anaerobic threshold and 10.0(2.1) ml.beat-1 at peak exercise (control v verapamil, both p less than 0.01). CONCLUSIONS: Digoxin was effective in reducing heart rate at rest, but failed to reduce it during exercise. Propranolol and verapamil reduced heart rate at all levels of exercise as well as at rest. Oxygen uptake during exercise (total exercise capacity) was not reduced with propranolol or verapamil; this was thought to have been accomplished by an increased oxygen pulse.

Aged↗