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Biomedical subjects

M Maeda

Publications and source records attributed to M Maeda.

At least 1,405 records · Page 78Linked to original sources
PubMed1982

Separation and determination of bile acids by high-performance liquid chromatography using immobilized 3 alpha-hydroxysteroid dehydrogenase and an electrochemical detector.

A high-performance liquid chromatographic method using an immobilized 3 alpha-hydroxysteroid dehydrogenase column and an electrochemical detector was developed for the determination of individual bile acids in serum and bile. Bile acids in the eluate from a Radial-Pak A column reacted with NAD in the enzyme column to generate NADH, which was monitored by a voltammetric detector after mixing with phenazine methosulphate solution. Each bile acid was measurable at the 20 pmole level at the highest sensitivity of the detector. The mean recoveries and reproducibilities of bile acids were 86.7-104.6% [coefficient of variation (C.V.) = 0.3-8.7%] within-assay and 83.8-103.4% (C.V. = 1.6-7.0%] between-assay.

3-Hydroxysteroid Dehydrogenases↗
PubMed1982

Fluoro norcholesterol analogues. Synthesis of 6 beta-(2'-fluoro) ethyl-19-norcholest-5(10)-en-3 beta-ol.

A synthetic route for labelling 6 beta-(2'-fluoro)ethyl-19-norcholest-5(10)-en-3 beta-ol (VII) with fluorine-18 was developed to evaluate the potential utility of VII as an adrenal imaging agent. 6 beta-p-Toluene-sulphonyloxymethyl-19-norcholest-5(10)-en-3 beta-ol acetate (I) was converted to the 6 beta-(2'-hydroxy)ethyl (VI) in a five-step process. The treatment of VI with N-N-diethyl (2-chloro-1,1,2,-trifluoroethyl)amine in methylene chloride and subsequent hydrolysis with base gave the required VII. Iodination of VI with triphenoxymethylphosphonium iodide followed by alkaline hydrolysis gave the 6 beta-(2'-iodo)ethyl (IX) which, on treatment with silver fluoride in acetonitrile, furnished the 6 beta-(2'-fluoro)ethyl (VII). Excellent conversion of the 6-beta-(2'-p-toluenesulphonyloxy)-ethyl (X) into VII was also achieved by heating with potassium fluoride for 2 hr in diethylene glycol in 76% yield, which is a readily applicable method for labelling with fluorine-18.

Chemical Phenomena↗
PubMed1982

Effect of microphase separated structure of polystyrene/polyamine graft copolymer on adhering rat platelets in vitro.

Rat platelet adhesion on microphase separated surface of polystyrene/polyamine graft copolymers (SA copolymers) was investigated. Shapes of adhering platelet were very much changeable in response to the mode of microphase separation of SA copolymer surfaces. We assume that the microphase separated structure of SA copolyer may regulate the shape change of platelet through its effect on a redistribution of proteins and/or lipids present at the plasma membrane of platelets.

Animals↗
PubMed1982

Salivary-type hyperamylasemia in primary lung cancer: observation of a possible precursor of the salivary-type isoamylase.

Although recent studies by column chromatography and electrophoresis showed that elevated amylase activity in the body fluids and tumor extracts in patients with primary lung cancer was mainly in the salivary-type isoamylase, neither mechanism nor mature of elevation of amylase have been clarified yet. This study was undertaken in order to make clear the nature of amylase elevated in the body fluids and tumor extracts of patients with primary lung cancer. In addition, amylase contained in the extracts of normal lungs and diseased lungs of patients who had died of various diseases was also studied. Our results revealed that amylase elevated in the body fluids and tumor extracts in patients with primary lung cancer was the salivary-type isoamylase and, moreover, that small amounts of salivary-type isoamylase in normal lung tissues and large amounts in diseased lung tissues were also contained. These facts suggested that salivary-type isoamylase was physiologically contained in normal lung tissues and large amounts in diseased lung tissues were also contained. These facts suggested that salivary-type isoamylase was physiologically contained in normal lung tissues and might be activated through pathological processes, such as inflammation, circulatory disturbance or tumor formation. Two peculiar isoamylases with cathodic mobility on polyacrylamide gel electrophoresis were found. One of them was so unstable that it was converted to the stable salivary-type isoamylase, suggesting the precursor of human salivary isoamylase.

Adenocarcinoma↗
PubMed1982

Use of adenine nucleotide derivatives to assess the potential of exo-active-site-directed reagents as species- or isozyme-specific enzyme inactivators. 3. Synthesis of adenosine 5'-triphosphate derivatives with N6- or 8-substituents bearing iodoacetyl groups.

Several series of N6- or 8-substituted derivatives of adenosine 5'-triphosphate (ATP) were synthesized. N6-(omega-Aminoalkyl) derivatives of adenosine 5'-monophosphate (AMP) were converted into their omega-N-carbobenzyloxy derivatives, and these were converted, via the 2',3'-O-carbonyl derivatives of their 5'-phosphorimidazolidates, into the corresponding ATP derivatives. Hydrogenolytic removal of the carbobenzyloxy groups, followed by iodoacetylation of the omega-amino groups with N-(iodoacetoxy)succinimide, gave N6-R-ATP, where R = (CH2)nNHCOCH2I (n = 2--8) or (CH2)nCON)CH3)(CH2)mN(CH3)CO(CH2)nNHCOCH2I (n = m = 3; n = 3, m = 4; n = 4, m = 3; n = m = 4). Condensation of N6-(omega-aminoalkyl) derivatives of AMP with N-hydroxysuccinimide esters of omega-[N-(carbobenzyloxy)amino] carboxylic acids gave N6-(CH2)nNHCO(CH2)mNH-Cbz derivatives of AMP which, upon conversion to the corresponding derivatives of ATP, followed by removal of the carbobenzyloxy group and iodoacetylation, as described above, gave N6-(CH2)nNHCO(CH2)mNHCOCH2I-ATP derivatives (n = 3, m = 5 or 6; n = 4, m = 5; n = 6, m = 1--6). The same sequence of reactions starting with N6-[omega-(methylamino)alkyl] derivatives of N6-CH3-AMP gave N6-CH3, N6-(CH2)nH(CH3)CO(CH2)mNHCOCH2I derivatives of ATP (n = 4, m = 3, 5 or 6; n = 6, m = 5 or 6). Reaction of alpha, omega-diaminoalkanes with 8-Br-ATP gave 8-NH(CH2)nNH2 derivatives of ATP, which upon iodoacetylation gave 8-NH(CH2)nNHCOCH2I derivatives of ATP (n = 2, 4, 6, or 8). Substrate and inhibitor properties indicated that the ATP derivatives are potential exco-ATP-site-directed inactivators of hexokinases, adenylate kinases, and pyruvate kinases.

Adenosine Diphosphate↗
PubMed1982

Use of adenine nucleotide derivatives to assess the potential of exo-active-site-directed reagents as species- or isozyme-specific enzyme inactivators. 4. Interactions of adenosine 5'-triphosphate derivatives with adenylate kinases from Escherichia coli and rat tissues.

Adenosine 5'-triphosphate (ATP) derivatives of the types N6-R-ATP [R = (CH2)nHNCOCH2I, (CH2)nNHCO-(CH2)mHNCOCH2I, or (CH2)nCON(Me)(CH2)mN(Me)CO(CH2)nNHCOCH2I], N6-Me-N6-R-ATP [R = (CH2)nN-(Me)CO(CH2)mNHCOCH2I], and 8-R-ATP [R = NH(CH2)nNHCOCH2I] with 5--19 spacer atoms between N6 or C-8 and iodine have been evaluated as substrates, reversible inhibitors, and inactivators of adenylate kinase (AK). With Escherichia coli AK, the derivatives were noncompetitive inhibitors, Ki = 4.7--7.3 mM, with little affinity for the ATP site, and N6-(CH2)nNHCOCH2[-ATP (n = 5 or 6) effected progressive inhibitions that were not ATP site directed. With rat muscle AK (M-AK), some compounds had slight affinity for the ATP site as evidenced by weak substrate activity with as much as 8 spacer atoms, but all compounds tested were weak noncompetitive inhibitors; Ki = 6--12 mM vs. ATP. The ATP derivatives, notably N6-(CH2)8NHCOCH2I-ATP, mediated a progressive inhibition of M-AK, which was abolished by substitution of hydrogen for the iodine and thus presumably involves alkylation of the enzyme. The inhibition appeared not to be ATP site directed because kinetic analysis indicated a random bimolecular enzyme-inhibitor reaction and because N6-(CH2)8NHCOCH2I-AMP and its adenosine counterpart, which have relatively low affinity for the ATP site, were more effective than N6-(CH2)8NHCOCH2I-ATP. The ATP derivatives were substrates (KM = 0.4--1.6 mM) and/or competitive inhibitors (Ki = 0.3--6.2 mM) vs. ATP of rat isozymes AK II or III. Exposure of AK II or III for 6 h, 22 degrees C, at pH 7.6 to 10 mM levels of the 1:1 Mg complexes of 25 of the ATP derivatives led in no case to progressive enzyme inhibition, suggesting the absence near the ATP sites of nucleophilic groups suitably positioned for alkylation.

Adenosine Triphosphate↗
PubMed1982

Human T-cell leukemia-lymphoma virus (HTLV) is in T but not B lymphocytes from a patient with cutaneous T-cell lymphoma.

A human type C retrovirus, designated HTLV, previously was isolated from or identified in some patients with leukemias and lymphomas of mature T lymphocytes. HTLV is genetically and serologically distinct from any known animal retroviruses. The absence of HTLV proviral sequences in DNA from normal humans showed that HTLV is not a ubiquitous endogenous (germ-line transmitted) virus of humans. Antibodies to HTLV core proteins have been identified in some people with T-cell neoplasias and are particularly prevalent in Japanese with adult T-cell leukemia, suggesting that HTLV is acquired horizontally. However, it was possible that HTLV is transmitted through the germ line of some (possibly rare) families and is then expressed in the HTLV- positive malignancies. An opportunity to study this question was provided by the development of several T-cell lines and a B-cell provided by the development of several T-cell lines and a B-cell line from one HTLV-positive patient with a cutaneous T-cell lymphoma. Here we report that HTLV proteins or nucleic acids (or both) are found in three independently derived T-cell lines, all shown by HLA typing to have originated from the patient. In contrast, the B-cell line, the identity of which was also ascertained by HLA typing, contained no detectable HTLV protein, RNA, or proviral DNA. Because the sensitivity of the latter assay is more than sufficient to detect one proviral equivalent per haploid genome, the results indicate that HTLV was not transmitted to this patient through the germ line but rather was acquired by infection.

B-Lymphocytes↗
PubMed1982

Effect of alterations in thyroid status on the metabolism of thyroxine and triiodothyronine by rat pituitary gland in vitro.

The metabolism of thyroxine (T(4)) was studied in slices of rat pituitary gland and liver from the same animal incubated in vitro with [(125)I]T(4) and 10 mM dithiothreitol. In the pituitary gland, generation of (125)I-labeled 3,5,3'-triiodothyronine (T(3)), as well as overall T(4) degradation, increased significantly at 24 h after thyroidectomy and by 2 wk were approximately five times control values. Conversely, following a single injection of T(3) (1.5 mug/100 g body wt), values for both functions were significantly decreased at 4 h, and reached a nadir of approximately 20% of control values at 12 and 24 h. Net T(3)-neogenesis accounted for approximately 70% of T(4) degradation in control pituitaries from intact rats. This proportion was increased by thyroidectomy and decreased by T(3) replacement. Indirect evidence indicated that thyroidectomy decreased, and T(3) administration increased, non-T(3) generating pathways of T(4) metabolism, probably 5-monodeiodination leading to formation of 3,3'5'-triiodothyronine (rT(3)). As judged from studies by others, the prompt changes in T(4) metabolism that followed thyroidectomy or T(3) administration could not be explained by changes in pituitary cell type. Changes in T(3)-neogenesis in liver were the converse of those in pituitary, and were much slower to occur. In the thyroidectomized rat, administration of cycloheximide resulted in an approximately 60% inhibition of pituitary T(3)-neogenesis and T(4)-degradation at 4 h, a time-course of inhibition similar to that produced by T(3). Unlike T(3), cycloheximide did not alter the proportion of T(4) degradation that could be accounted for by T(3) neogenesis, and appeared, therefore, to inhibit both T(3) generating and non-T(3) generating pathways. The time-course of the inhibitory effect of cycloheximide on the incorporation of [(3)H]leucine into hemipituitaries in vitro was parallel to its effect on T(3)-neogenesis. The inhibition of T(3)-neogenesis that occurred when T(3) and cycloheximide were given together did not exceed the effect of T(3) alone, suggesting a common mechanism of action of the two agents. FROM THE FOREGOING INFORMATION, THE FOLLOWING TENTATIVE CONCLUSIONS ARE DRAWN: (a) turnover of the 5'-monodeiodinase for T(4) in rat pituitary is rapid, substantially more so than in liver; (b) thyroidectomy enhances, and T(3) inhibits, the conversion of T(4) to T(3) in the pituitary; these manipulations have opposite effecs on the non-T(3) generating pathways of T(4) metabolism, probably the 5-monodeiodination of T(4) that produces rT(3); (c) these changes are probably the result of parallel effects on the synthesis of the corresponding enzymes; (d) the changes in T(3)-neogenesis described may permit an intrapituitary feedback mechanism that damps the changes in TSH secretion mediated by classical feedback regulatory control; (e) the effects of hypothyroidism and T(3)-replacement on T(3)-neogenesis and overall T(4) degradation in liver were opposite to those produced in the pituitary. Hence, among differing tissues, the same stimuli may produce greatly different responses in pathways of peripheral T(4) metabolism, thus making possible differing metabolic sequelae within each.

Animals↗
PubMed1982

Glucose-dependent insulinotropic action of cholecystokinin and caerulein in the isolated perfused rat pancreas.

The effect of pure natural porcine cholecystokinin (CCK) and synthetic caerulein on endocrine and exocrine pancreatic secretion was investigated in the isolated perfused rat pancreas in the presence of physiological concentrations of glucose. CCK (0.25 mU/ml) or caerulein (0.01 ng/ml) potentiated the insulin secretion induced by 5.6 mM glucose; a significant increase in pancreatic exocrine secretion was also observed at these doses of CCK or caerulein. Further increases in the concentration of CCK (0.25 to 1 mU/ml) or caerulein (0.01 to 1 ng/ml) resulted in dose-dependent increases in both insulin and pancreatic exocrine secretion. The effectiveness of CCK and caerulein as insulinotropic agents depended on the glucose concentration; they were more effective at higher concentrations of glucose. Thus, CCK or caerulein significantly and coincidentally stimulated both insulin secretion and pancreatic exocrine function if 5.6 mM or more glucose is present, whereas in previous studies using 2.8 mM glucose, stimulation of insulin secretion was elicited only with concentrations of the peptides supramaximal for an effect on pancreatic exocrine secretion. CCK may contribute to the entero-insular axis.

Amylases↗
PubMed1982

Enzyme immunoassay of cyclazocine using peroxidase as label.

A sensitive enzyme immunoassay for the determination of serum or urinary cyclazocine was developed. Horseradish peroxidase was used as the labelling enzyme; it was conjugated with cyclazocine derivatives by the mixed anhydride method. After the immune reaction, bound and free fractions were separated by a double-antibody solid-phase method, using Sepharose 4B gel coupled with purified IgG from goat anti-rabbit IgG serum. The enzyme activity was measured fluorophotometrically, with p-hydroxyphenyl propionic acid and hydrogen peroxide as substrates. The correlation coefficients verified that there was excellent agreement between the results obtained by the new enzyme immunoassay and those of radioimmunoassay (r=0.92) and gas chromatography-mas spectrometry (r=0.94).

Cyclazocine↗
PubMed1982

Synthesis and antitumor activity of seleno- and thio-purines complexed with cis-diamminoplatinum (II).

cis-Diamminoplatinum (II) complexes with selenoguanine, thioguanine, 6-thioxanthine, or 6-mercaptopurine were synthesized by the reaction of stoichiometric amounts of selenopurine or thiopurine with aquated cis-dichlorodimmineplatinum (II) in slightly acidic medium, and their antitumor activity was studied against L1210 cells in mice. These compounds exhibited a medium antitumor activity with very low toxicity. The antitumor activity was dependent on the nature of the purine ligand. These complexes were very stable in various aqueous solvents at 37 degrees C for 10 d but not in the presence of mouse serum. The mechanism of the action effected by the complex is not clear. However, the slow release of an antitumor active purine from the complex, SeG-Pt (NH3)2, was observed.

Animals↗
PubMed1982

[Phase II study on peplomycin for esophageal cancer].

For the purpose of verifying the effectiveness of peplomycin, one of the derivatives of bleomycin, against carcinoma of the esophagus and the safety of it, the analysis of the data for total 113 cases collected from 25 institutions in Japan was made. The results are as follows. It was effective in 19 out of 74 evaluable cases of carcinoma of the esophagus (25.7%). In case of treatment with peplomycin alone, it was effective in 6 out of 39 cases (15.4%). In case of the combination treatment with peplomycin and some other therapy, it was effective in 13 out of 35 cases (37.1%). As for the side effects, the incidence of fever was the highest in both the cases of peplomycin alone and the combination treatment such as 39.6% and 37.0%, respectively. Anorexia, nausea, vomiting, respiratory symptoms and tiredness were found in relatively many cases. In the clinical laboratory tests, the vital capacity after the treatment tended to be lower than that before the treatment, but there was little change in the hematological tests, pulmonary function test and renal function test.

Adult↗