[Roferon-A. Canferon-A. Interferon alpha-2A (genetic recombination)].
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Animals↗
Biomedical subjects
T Taguchi
Publications and source records attributed to T Taguchi.
[Malignancy grading in breast cancer as assessed by nuclear DNA content].
The relationship between nuclear DNA content measured by cytofluorometry and the prognostic factors, especially the histological lymph node metastasis was investigated in patients with breast cancer. Nuclear DNA content was measured in 82 cases to evaluate its clinical significance concerning the malignancy grading. Histograms of DNA content were classified into two basic ploidy patterns based on presence or absence of a prominent peak at the 2c (diploid) region. D type (diploid type) which had a prominent peak at the 2c region resembled the histogram pattern of normal cells more closely than N type (non-diploid type). The rate of lymph node metastasis of N type (57.4%) was significantly higher than that of D type (28.6%) (p less than 0.05). The rate of lymph node metastasis of N type was higher than D type regardless of the tumor size or histological types. The five year cumulative survival rate of D type (91.7%) was significantly higher than that of N type (68.2%) (p less than 0.05). Despite the lymph node metastasis, the survival rate of D type was higher than that of N type. From a view point of the relationship between nuclear DNA content and lymph node metastasis, breast cancers of D type might be much safer indications for modified radical mastectomy. From this study, it was suggested that the measurement of nuclear DNA content of the breast cancer would bring the important informations about the malignancy grading and decision of the operative procedure.
Adult↗
[Basic studies in intra-arterial chemotherapy with degradable starch microspheres (DSM) on human gastric cancer xenografts in nude rats].
Enhancement of the antitumor effect of adriamycin (ADR) was investigated by using degradable starch microspheres (DSM) and pharmacokinetics of ADR in combination with DSM. An intra-arterial chemotherapy model of the nude rats transplanted of human cancer xenografts (H-154 gastric cancer) in the lower limbs was used for this study. Drug was administered through a catheter inserted into the carotid artery with the tip in the common iliac artery. DSM 30 mg/kg, which causes temporary arrest of blood flow in the tumor, had an only weak effect on tumor growth, whereas. DSM 30 mg/kg, mixed with ADR 3 mg/kg solution, was more effective than ADR solution. Furthermore, DSM 30 mg/kg mixed with ADR 3 mg/kg had a greater effect on the tumor growth than DSM 15 mg/kg mixed with ADR 3 mg/kg. In the pharmacological study, increase of the regional uptake of ADR and decrease of systemic distribution of ADR were recognized in some degree. It seems that embolization by DSM, retention of ADR in regional tissues and cytotoxic effect of ADR contributed to such a strong effect of ADR mixed with DSM on tumor growth.
Animals↗
A subpopulation of embryonic telencephalic neurons survive and develop in vitro in response to factors derived from the periphery.
Denervated chick muscle contains factors that enhance neurite outgrowth in cultures of embryonic chicken spinal neurons. Chromatography of muscle extract on a column of DEAE-Sepharose yielded a fraction which retained most of the starting neurite-promoting activity. This DEAE fraction was tested for its activity on neurons from other regions of the central nervous system of 5-day-old chicken embryos. Both neurite outgrowth and survival of telencephalic neurons in vitro were greatly enhanced when the DEAE fraction was added at protein concentrations around 1 microgram/ml. When cultures were prepared from embryos later than 6 days in ovo, the effects of the DEAE fraction progressively diminished with age. Neurons from the embryonic diencephalon, mesencephalon and rhombencephalon were not responsive to the DEAE fraction, although they all developed neurites on a laminin substratum. Similar neurite-promoting activities for telencephalic neurons were found in extracts of neonatal brain, liver and heart, but not lung.
Animals↗
Induction of zinc-thionein by estradiol and protective effects on inorganic mercury-induced renal toxicity.
The castrated or unoperated male rats received an intravenous injection of HgCl2 at a dose of 0.7 mg/kg of body weight (b.w.) after pretreatment with 30% ethanol or estradiol dissolved in 30% ethanol at a dose of 0.5 mg/kg b.w. subcutaneously twice a day for six consecutive days. Renal total protein, gamma-GTP and K excretion in the rats treated with Hg and estradiol were significantly lower than the corresponding values in the rats treated with Hg alone, suggesting that pretreatment with estradiol ameliorates the renal toxicity of Hg in male rats. Pretreatment with estradiol significantly increased Hg and Hg-thionein(Hg-MT) concentrations in the renal cortex of the animals treated with Hg, though in the liver this agent did increase the Hg-MT without elevation of Hg concentration. Treatment with estradiol alone (0.5 mg/kg, s.c., twice a day, for six consecutive days) significantly increased the zinc-thionein (Zn-MT) concentration in the kidney and liver. Simultaneous treatment with 10(-5) M estradiol and Hg in human amniotic-fluid cells caused a significant increase in the uptake of Hg and the synthesis of Hg-MT, suggesting that estradiol may directly stimulate an accumulation of Hg into the cells and the synthesis of Hg-MT. Together, all of the above findings suggest that pretreatment with estradiol may increase the uptake of Hg, which in turn leads to the increase in the Hg-MT concentration. The induction of Zn-MT by pretreatment with estradiol may account for the protective effect of estradiol on Hg-induced renal toxicity.
Animals↗
Determination of pseudo-alpha- and pseudo-beta-DL-glucose by gas-liquid chromatography, high-performance liquid chromatography, and enzymatic colorimetry with glucose 2-oxidase.
Three methods have been developed for measuring pseudo-alpha- and pseudo-beta-DL-glucose (pseudo-beta-D-glucose), synthetic compounds in which the ring oxygens of alpha- and beta-DL-glucose (beta-D-glucose) have been replaced by a methylene group. Moderate sensitivity in the determination of these pseudo-glucoses dissolved in human serum was obtained by GLC (0.1 nmol) and HPLC (0.5 nmol). The colorimetric determination with glucose 2-oxidase, peroxidase, and 2,2'-azino-di-(3-ethylbenzothiazoline-6-sulfonic acid) was satisfactory for the assay of pseudo-alpha- and pseudo-beta-DL-glucose (respective sensitivities: 25 and 5 nmol). The addition of hexokinase to the colorimetric assay system made it possible to eliminate glucose present in the sample, such as serum, and the remaining pseudo-alpha- or pseudo-beta-DL-glucose in the sample solution could then be measured by a colorimetric method using glucose 2-oxidase. The methods described can be used for biochemical studies involving pseudo-alpha- and pseudo-beta-DL-glucose.
Chromatography, Gas↗
Quantitation of urinary metabolites of toluene, xylene, styrene, ethylbenzene, benzene and phenol by automated high performance liquid chromatography.
An automated high performance liquid chromatographic method (HPLC) for the direct determination of urinary concentrations of hippuric acid (HA), and o-, m- and p-methyl hippuric acids (MHAs), metabolites of toluene and o-, m-, and p-xylenes, and of urinary phenyl glyoxylic acid (PGA) and mandelic acid (MA), metabolites of styrene or ethylbenzene, is described. Methanol was added to urine, the mixture was centrifuged and the supernatant was injected into HPLC. A stainless-steel column packed with octadecyl silanized silicate was used and the mobile phase was a mixed solution of 5 mM potassium phosphate monobasic/acetonitrile (90/10). The method is simple and specific. Urine can be analyzed without solvent extraction. Analysis can be performed satisfactorily within 45 min for samples containing HA, MHAs, PGA and MA, and within 15 min for those containing HA, PGA and MA. Another automated HPLC method for the determination of urinary concentrations of phenylsulfate (PhS) and phenylglucuronide (PhG), metabolites of benzene and phenol, is also described. Urine was centrifuged and the supernatant was injected into HPLC. A column packed with octadecyl silicate and a mobile phase of 50 mM of potassium phosphate monobasic/acetonitrile (85/15) were used. The whole analyses and quantitative determination can be performed within 15 min for samples containing PhS and PhG in the worker's urine with a simple mobile phase. The accuracy and precision in the present methods by the use of automated HPLC were satisfactory.
Autoanalysis↗
High performance liquid chromatographic procedure for quantitative determination of urinary delta-aminolevulinic acid as indices of lead exposure.
A high performance liquid chromatographic method for the determination of delta-aminolevulinic acids (ALA) in urine, is described. 2-Methyl-3 carbmethoxy-4-(3-propionic acid) pyrrole was produced by the condensation of ALA with methylacetoacetate (MAA) while heating. The methylacetoacetate could be replaced by ethylacetoacetate. The ALA pyrrole thus obtained was injected into high performance liquid chromatography (HPLC). A stainless-steel column packed with octadecyl silanized silica gel was used. The mixed solution of acetonitrile/50 mM KH2PO4 (adjusted to pH 2.5 with 0.001 volumes of 85 g/dl H3PO4) (20/80) was a favorable mobile phase for the separation of ALA. Amino acetone pyrrole was produced by the condensation of amino acetone with methyl acetoacetate. The amino acetone pyrrole appeared later than ALA pyrrole on HPLC. The method is simple and specific. It has a lower detection limit of 0.2 ng on column. The analysis and quantitative determination of one specimen can be performed within 20 min. Mean ALA concentration of normal urine by HPLC was 1.18 mg/g creatinine.
Adult↗
Phase I study of recombinant human tumor necrosis factor.
A phase I clinical and pharmacokinetic study of recombinant human tumor necrosis factor (rH-TNF) was conducted in a single dose schedule in 33 patients with advanced cancer. rH-TNF was given by i.v. infusion over 30 min with a starting dose of 1 x 10(5) units/m2. The dose was escalated up to 16 x 10(5) units/m2 according to the modified Fibonacci scheme. Toxic effects were similar but not identical to those reported with interferons and interleukin-2, and included fever, rigors, nausea and vomiting and anorexia in a non-dose-dependent manner, and hypotension, leukocytosis, thrombocytopenia and transient elevation of transaminases (SGOT and SGPT) in an approximately dose-dependent manner. DIC syndrome was observed in one patient who had received 16 x 10(5) units/m2. The dose-limiting toxicities were hypotension, thrombocytopenia and hepatotoxicity, and the maximum tolerated dose in a single i.v. infusion of rH-TNF appeared to be 12 x 10(5) units/m2 when thrombocytopenia and elevation of SGOT and SGPT were taken as the dose-limiting toxicities. However, if hypotension was included, the maximum safely tolerated dose appeared to be 5 x 10(5) units/m2.
Adult↗
Isolated unilateral absence of left pulmonary artery with peribronchial arteriovenous malformation showing recurrent hemoptysis.
Unilateral absence of a pulmonary artery is an uncommon condition and usually complicated by a cardiac anomaly. Our case is a rare one who showed the absence of the left pulmonary artery with left aortic arch and without cardiac anomaly. He suffered from recurrent hemoptysis and pneumonia since he was 9 months old. Angiography revealed peribronchial arteriovenous malformation of the affected lung which was supplied from subclavicular arteries and bronchial arteries. Although he was treated by operative ligation and angiographic embolotherapy of the supplying systemic arteries, the repeated the attacks of massive hemoptysis and necessiated left pneumonectomy at 10 years of age.
Arteriovenous Malformations↗
A comparative study of IgA nephritis in Japan and Germany. An approach to its geopathology.
A comparison of clinical and pathological features in 357 Japanese cases and 29 German cases of primary IgA nephritis was performed. Male population was higher than female in the German cases (2.6:1), while it was almost even in the Japanese (1.07:1) (p less than 0.05). Age distribution was similar. At the time of detection of the disease, asymptomatic patients were more frequent in Japanese (78%) than in German cases (60%) (p less than 0.05). The most common findings were mild mesangial proliferative glomerulonephritis in both series (65% in Japanese, 61% in German cases), but severe histological changes were more frequent in German patients (25%) than in the Japanese (16%). The incidence of IgA nephritis in primary glomerulonephritis was 38.8% in Japanese and 11.9% in German cases, and the incidence in mesangial proliferative glomerulonephritis was 65.6% in Japanese and 29.2% in German patients (p less than 0.01). It is considered that the divergent incidence of IgA nephritis may be a real geopathological event, although its variability may be intensified by different indications for biopsy or different population. It is suggested that various possible pathogenetic agents may be irregularly distributed throughout the world, which may contribute to the divergent clinical and pathological manifestations.
Adolescent↗
Interferon treatment of human stomach and breast carcinoma xenografts in nude mice.
Comparative effects of natural and recombinant interferons (IFNs)-alpha and -beta on xenografted human gastric and breast carcinoma lines in nude mice were studied. The lines were sensitive to IFNs. The breast carcinoma lines were more sensitive than the gastric carcinoma lines to IFNs. Natural IFN-beta was more effective than the other three IFNs on the gastric carcinoma lines. One breast carcinoma line was more sensitive to IFN-alpha whereas the other was more sensitive to IFN-beta. Large doses and frequent injections of IFNs were necessary for optimal effectiveness.
Animals↗
Extracts of muscle biopsies from patients with spinal muscular atrophies inhibit neurite outgrowth from spinal neurons.
Preparations derived from embryonic and neonatal chick muscle enhance neurite outgrowth when added to cultures of embryonic chick spinal neurons. In the presence of soluble extracts of biopsied muscle from 15 of 20 patients with spinal muscular atrophy (SMA), the in vitro neurite-promoting activity of neonatal chick muscle was inhibited. There was no comparable inhibition using extracts from 20 age-matched pathologic or morphologically normal controls. The neurite-promoting activity in media conditioned by embryonic myotubes was not inhibited by extracts of the SMA group.
Animals↗
Pharmacokinetic studies on 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077). III. Pharmacokinetics of a new nitrosourea antitumor agent TA-077 in humans (a phase I study).
A new nitrosourea antitumor agent TA-077, 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea, was intravenously administered to 15 cancer patients at doses ranging from 7 to 100 N (1 N = 30 mg/m2) in a phase I clinical trial. Time courses of blood concentrations of TA-077 and its active metabolite TA-G, 3-beta-D-glucopyranosyl analog of TA-077, were followed. The TA-G concentration reached a maximum at 7.0 +/- 2.3 min, and decreased thereafter with a half-life of 12.9 +/- 2.8 min. The time-course patterns and various pharmacokinetic parameters of TA-077 and TA-G were similar to those in the guinea pig, which, like humans, lacks plasma maltase activity. The 2 h-urinary excretion rate of TA-G in the above patients ranged from 0.15 to 7.7% of the dose. The areas under the concentration-time curve and maximal concentration values were both linearly correlated to the dose with correlation coefficients of 0.78 and 0.82, respectively. Repeated administration of TA-077 (29 to 40 N) for 5 or 6 consecutive days did not affect the pharmacokinetic parameters of TA-077 and TA-G in 7 cancer patients except for slight increases in the half-life and area under the curve of blood TA-G.
Adult↗
Mutarotation of D-glucose in body fluids and perfused rat liver.
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Adult↗
Synthesis and biological activity of fluorine-modified platelet activating factors.
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Animals↗
Blood vascular architecture of the rat cerebral hypophysis and hypothalamus. A dissection/scanning electron microscopy of vascular casts.
Complete casts of the hypophyseal and hypothalamic blood vascular beds of newborn, pubescent, adult and aged rats were produced by infusion of low viscosity methacrylate media, dissected under a binocular light microscope, and observed with a scanning electron microscope. The primary capillary plexus projected capillary loops into the median eminence and infundibular stalk. These loops were composed of anastomosing capillaries, being numerous in the central area of the anterior lip of the median eminence. The well developed long loops received their proper afferent arterioles from the arterial terminals in the primary plexus, and emitted their proper efferent venules continuous with the long portal vessels. The loops in newborn rats were poorly developed, appearing as simple ball-like protrusions of the capillaries of the primary plexus. Many branches of the anterior, middle and accessory middle hypophyseal arteries penetrated the primary plexus, and ascended as infundibular ascending arterioles in the median eminence and infundibular stalk. These infundibular ascending arterioles continued into the capillary bed of the hypothalamus, especially in its basilar and peri-ventricular areas. The subependymal capillary network was fairly independent, and located dorsal to the loops. This network received some of the infundibular ascending arterioles, and emitted infundibular descending venules continuous with the long portal vessels. The subependymal network also received the infundibular descending arterioles from the hypothalamic arteries, and emitted the infundibular ascending venules continuous with the hypothalamic veins. Thus, neither a feedback nor a retrograde portal route from the hypophyseal capillaries to the hypothalamic capillaries was noted. The capillary bed of the pars tuberalis was observed only in the adult and aged rats; it was a very coarse network which was derived from the primary capillary plexus and connected to the secondary capillary plexus.
Aging↗
Lysine-mediated tissue osmication in combination with a tannin-osmium conductive staining method for non-coated scanning electron microscopy of biological specimens.
Glutaraldehyde fixed rat kidney blocks showed no charging effect when treated with lysine and osmic acid and viewed in a scanning electron microscope using an acceleration voltage of 5-30 kV and a specimen current of 1 X 10(-10) A. The podocyte processes and endothelial micropores of the glomerulus were visible without metal coating. Glutaraldehyde fixed, tannin-osmium impregnated and lysine-osmium treated specimens also showed no charging effect in the scanning electron microscope, yielding instead much clearer scanning images which were comparable to those obtained from gold-coated specimens or from tannin-osmium-thiocarbohydrazide-osmium impregnated specimens (Murakami and Jones, 1980).
Animals↗