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Biomedical subjects

J Goto

Publications and source records attributed to J Goto.

At least 145 records · Page 8Linked to original sources

Studies on steroids. CCLII. Separation and characterization of 3-oxobile acids in serum by high-performance liquid chromatography with fluorescence detection.

The separation of unconjugated and glycine- and taurine-conjugated bile acids with a C-3 oxo group has been carried out by high-performance liquid chromatography on a reversed-phase column. The chromatographic behaviour of these 3-oxobile acids was dependent on the number and positions of hydroxyl groups and the structure of the side-chain. The newly developed method has been applied to the characterization of 3-oxobile acids in biological fluids. The bile acid fraction was obtained from a serum specimen by passing it through a Sep-Pak C18 cartridge. 3-Oxobile acids were derivatized quantitatively to fluorescent oximes through the oxo group by treatment with O-(2-anthrylmethyl)hydroxylamine. The derivatives were separated into the unconjugated and glycine- and taurine-conjugated fractions by ion-exchange chromatography on a lipophilic gel, piperidinohydroxypropyl Sephadex LH-20. Subsequent resolution of each fraction into individual 3-oxobile acids was achieved by chromatography on a Nova-Pak Phenyl column using 3% methanol in 0.3% potassium phosphate buffer (pH 7.0)-acetonitrile (8:5, v/v) as the mobile phase. The derivatized 3-oxobile acids were monitored by fluorescence detection (excitation wavelength 260 nm and emission wavelength 405 nm), the limit of detection being 20 fmol. Glycine- and taurine-conjugated 7 alpha,12 alpha-dihydroxy- and 7 alpha-hydroxy-3-oxo-5 beta-cholanoic acids in human serum were unambiguously idenitified on the basis of their chromatographic behaviour using mobile phases of different pH values.

Bile Acids and Salts↗

A case of adult onset pure pallidal degeneration. I. Clinical manifestations and neuropathological observations.

We present a case of adult onset progressive neurodegenerative disease with a selective involvement in the globus pallidus (GP). The main symptom was extreme slowness in motion without rigidity, which was distinct from akinesia of parkinsonism. Dystonic posture developed in neck and fingers and mild rigidospasticity appeared in a later stage. Neuropathological examination shows a selective neuronal loss with gliosis in GP and degeneration of the efferent fibers. Although the subthalamic nucleus is slightly atrophic with minimal gliosis, there is no neuronal loss in the nucleus. The rest of the structures are pathologically insignificant. Because the pathological change is confined to GP neurons and their efferent fibers, we think that the marked slowness in motion and dystonic posture are ascribable to the selective GP lesion. A degenerative neurological disorder preferentially involved in GP was reported as pure pallidal degeneration (PPD). The onset of the PPD was in the first or second decades and the main symptoms were choreoathetosis, torsion dystonia and progressive rigidity. These distinct clinical features seemed to distinguish the present case from the previously described PPD. Therefore, we would like to call our case "adult onset" PPD. Clinicopathological correlation is discussed.

Adult↗

Potential bile acid metabolites. 17. Synthesis of 2 beta-hydroxylated bile acids.

The 2 beta-hydroxylated derivatives of lithocholic, chenodeoxycholic, deoxycholic, and cholic acids were synthesized from the respective parent bile acids by established procedures. The principal reactions involved were (1) bromination of 3-oxo formylated bile acids in N,N-dimethylformamide, (2) rearrangement and substitution of the resulting 4 beta-bromo-3-oxo derivatives to the 2 beta-acetoxy-3-oxo compounds with potassium acetate, and (3) reduction to the 2 beta-acetoxy-3 alpha-hydroxy compounds with tert-butylamine-borane complex. As for the prepared 2 beta-hydroxylated bile acids with a diequatorial trans-glycol structure, proton and carbon-13 nuclear magnetic resonance spectroscopic and gas-liquid chromatographic/mass spectrometric properties are discussed.

Acetates↗

Synthesis and platelet aggregation inhibitory activities of 3-(2-oxopropylidene)azetidin-2-one derivatives. II.

A series of 3-acylidene-4-methylazetidin-2-one derivatives bearing various substituents at the 1-position of the azetidin-2-one ring was synthesized. These compounds were evaluated for platelet aggregation inhibitory activities. Most of the compounds synthesized showed potent inhibitory activities against rabbit platelet aggregation induced by adenosine diphosphate or collagen in vitro. Structure-activity relationships are also discussed.

Animals↗

Studies on beta-lactam antibiotics. XIX. Structure-activity relationships of cephalosporins having a thiadiazolylthiomethyl group at the C-3 side chain.

The synthesis and antibacterial activity of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(hydroxy or alkoxy)iminoacetamido]cephalosporins with various thiadiazolylthiomethyl moieties at the 3-position are discussed. Of the compounds (1a-1e, 7a-7d), 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-hydroxyiminoacetamido]-3-[(1,2 ,4- thiadiazol-5-yl)thiomethyl]cephalosporin (1d: FK312) exhibited the highest activity against Gram-positive and Gram-negative bacteria, especially, against methicillin-resistant Staphylococcus aureus. Furthermore, the pharmacokinetic profiles of the compound 1d showed longer serum levels than that of ceftriaxone in rats.

Anti-Bacterial Agents↗

Potential bile acid metabolites. XVIII. Synthesis of stereoisomeric 3,6,12 alpha-trihydroxy-5 beta-cholanoic acids.

Two new 6-hydroxylated bile acids, 3 beta, 6 alpha, 12 alpha- and 3 beta, 6 beta, 12 alpha-trihydroxy-5 beta-cholanoic acids, were synthesized from deoxycholic acid. In addition, their C-3 epimers, 3 alpha, 6 alpha, 12 alpha- and 3 alpha, 6 beta, 12 alpha-trihydroxy acids, were prepared by a new route. The principal reactions used were 1) 6 beta-hydroxylation of 3-methoxy-3,5-dienes with m-chloroperbenzoic acid in aqueous dioxane; 2) catalytic hydrogenation of the resulting 6 beta-hydroxy-3-oxo-4-enes to the 6 beta-hydroxy-3-oxo-5 beta compounds with palladium on calcium carbonate catalyst in ethanol; and 3) stereoselective reduction of appropriate 3-oxo derivatives with potassium tri-sec-butylborohydride and tert-butylamine-borane complex. The thin-layer chromatographic, gas-liquid chromatographic, and high performance liquid chromatographic mobilities, and 1H- and 13C-nuclear magnetic resonance spectroscopic data of the four stereoisomers are presented. With this work all the 6-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, ursodeoxycholic, and cholic acids in the 5 beta series are now known and have been synthesized.

Bile Acids and Salts↗

Potential bile acid metabolites. 16. Synthesis of stereoisomeric 3 alpha,6,7,12 alpha-tetrahydroxy-5 beta-cholanoic acids.

New synthetic routes to the four possible stereoisomeric 3 alpha,6,7,12 alpha-tetrahydroxy-5 beta-cholanoic acids (and their methyl esters), one of which (3 alpha,6 alpha 7 beta,12 alpha) is new, and some related compounds are described. In addition, the 5 alpha-epimer of the new acid was obtained. The final products were obtained in high purity for use as reference compounds in the analysis of bile acids in human biologic samples. The results of analysis of the prepared stereoisomers by proton and carbon 13 nuclear magnetic resonance spectroscopies are briefly discussed along with the thin-layer and gas-liquid chromatographic properties.

Bile Acids and Salts↗

[A clinical and pathological study on varicella-zoster virus pneumonia].

A 48-year-old male with Adult T-cell leukemia (case 1) and a 57-year-old with acute lymphocytic leukemia (case 2) died of rapid progressive pneumonia and pleuritis. Histopathological findings of the lungs were multifocal hemorrhagic coagulation necrosis, and typical Cowdry type A and full type intranuclear inclusion bodies were observed in alveolar cells, bronchial cells, fibroblast, endothelial cells of small vessels, bronchial gland cells and pleural cells. Antigen against varicella-zoster virus (VZV) was positive in these cells by immunostaining, and the antigen was also demonstrated in other organs such as liver, spleen, pancreas, kidney, adrenal gland, esophagus, stomach, intestine and so on. Furthermore, cytomegalovirus was simultaneously superinfected lungs of both cases, and concomitant candida gastritis (case 1), aspergillus lung abscess and candida liver abscess (case 2) were observed. In the immunocompromised host VZV may involve the visceral organs and death may result from VZV pneumonia.

Bronchi↗

[HTLV-I associated interstitial pneumonia--a case report and bronchoalveolar lavage study].

A 70-year-old male was admitted to our hospital because of fever and dyspnea. The patient was seropositive for HTLV-I and ATL cells were seen in the peripheral blood in the percentage of 2-5. The proviral DNA was positive and the diagnosis of smoldering ATL was made. His chest X-ray film showed diffuse reticulo-nodular infiltrates in both lung fields. The lung tissue obtained by transbronchial lung biopsy showed the lymphocytic infiltrations in the alveolar septa and the submucosa of the bronchioles. Bronchoalveolar lavage (BAL) fluid showed an increased proportion of lymphocytes that consisted mainly of CD3+ DR+ cells and the CD4+/CD8+ ratio was 2.1 during exacerbation and 0.8 after steroid therapy. Anti-HTLV-I IgG and IgA antibodies were positive in both serum and BAL fluid by Western blotting method. It is suggested that T-lymphocyte alveolitis may occur in patients who are seropositive for HTLV-I and the immunological mechanism seems to be responsible.

Aged↗

Synthesis and platelet aggregation-inhibitory activities of novel 3-(2-oxopropylidene)azetidin-2-one derivatives. I.

Treatment of (E)-3-(2-hydroxypropylidene)-4-methyl-1-phenylazetidin-2-one (11) with 10% Pd/C gave (E)-(12), (Z)-3-(2-oxopropylidene)-4-methyl-1-phenylazetidin-2-one (13), 3,4-cis-(14a) and 3,4-trans-3-(2-oxopropyl)-4-methyl-1-phenylazetidin-2-one (14b). Among them, 12 and 13 were found to show potent inhibitory activities against rabbit platelet-rich plasma aggregation induced by adenosine diphosphate or collagen. Ring-expanded homologous derivatives and an acyclic analogue of 12 were also synthesized and tested for the biological activities. The azetidin-2-one skeleton bearing a 2-oxoalkylidene moiety at the 3 position was found to be essential for the platelet aggregation inhibitory activities of these compounds.

Animals↗

[Chromatographic determination of bile acids in biological fluids with sensitive and selective detection].

Separation and determination of bile acids in biological fluids by high-performance liquid chromatography are reviewed. The capacity ratios of bile acids on an ODS column were affected by the number, position and configuration of the hydroxyl group on the steroid nucleus, and the chromatographic behavior was markedly influenced by the pH of a mobile phase according to the conjugated form at C-24. A new pre-column derivatization reagent, 1-anthroyl nitrile, was developed and applied to the analysis of bile acids in biological fluids. Bile acids were derivatized through the 3 alpha-hydroxyl group into the corresponding esters, separated on an ODS column, and monitored by a fluorescence detector with detection limit of 20 fmol. The sensitive method for the determination of bile acids in biological materials by gas chromatography (GC) in combination with negative ion chemical ionization (NICI) mass spectrometry is also described. Of various derivatives for the carboxyl group, the pentafluorobenzyl (PFB) ester provided the highest value of the ratio of the negative to positive ion current. A characteristic carboxylate anion [M-181]- was produced as the most abundant ion by the loss of the PFB group in NICI. PFB esters of bile acids were further derivatized into the dimethylethylsilyl ethers and then separated by GC. The detection limit was 2 fg when the characteristic anion was monitored in the NICI mode. The preparation of 18O-labelled bile acids, as the internal standard for the trace analysis or the tracer for the metabolic study, was developed. Finally, the clean-up procedure for bile acids in biological fluids was investigated. The combined use of solid-phase extraction with a Sep-pak C18 or Bond Elut cartridge and group separation on a lipophilic ion-exchange gel, piperidinohydroxypropyl Sephadex LH-20, was found most effective for this purpose.

Bile Acids and Salts↗

Studies on steroids. CCXXXXV. Determination of 5 beta-cholestanoic acids in human urine by gas chromatography-mass spectrometry with negative ion chemical ionization detection.

A method for the determination of 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA) and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) in human urine by gas chromatography (GC) in combination with negative ion chemical ionization (NICI) mass spectrometry is described. Unconjugated, glycine- and taurine-conjugated DHCA and THCA labelled with 18O and 2H were used as internal standards. 5 beta-Cholestanoic acids in urine were extracted with a Sep-Pak C18 cartridge, separated into the unconjugated, glycine- and taurine-conjugated fractions by ion-exchange chromatography on piperidinohydroxypropyl Sephadex LH-20 and, following alkaline hydrolysis of conjugated forms, derivatization into the pentafluorobenzyl ester-dimethylethylsilyl ethers. Subsequent resolution of each fraction into DHCA and THCA was attained by GC on a cross-linked 5% phenylmethylsilicone fused-silica capillary column where 5 beta-cholestanoic acids were monitored with a characteristic carboxylate anion [M-181]- in the NICI mode using isobutane as a reagent gas. The method was applied to separation and determination of 5 beta-cholestanoic acids in urine from a patient with Zellweger syndrome and from healthy volunteers.

Bile Acids and Salts↗

A method for the simultaneous analysis of unconjugated and glycine-conjugated bile acids by capillary gas-liquid chromatography.

A method for the simultaneous analysis of unconjugated and glycine-conjugated bile acids by means of capillary gas-liquid chromatography without need for prior deconjugation is described. The method involves: i) the use of an aluminum-clad fused-silica capillary column coated with a very thin film (0.1 micron) of a highly thermostable bonded and crosslinked methyl polysiloxane, and ii) the analysis of the bile acids as their methyl ester-dimethylethylsilyl ether derivatives. This method, used to separate the major free and glycine-conjugated bile acids from human gall bladder bile, should be applicable for the analysis of other biological fluids.

Bile Acids and Salts↗

[A histopathological study on pseudomonas pneumonia diagnosed by immunostaining with monoclonal antibody].

Pseudomonas pneumonia is one of the fatal opportunistic infections. We examined Pseudomonas aeruginosa in the autopsied lung tissues by the immunostaining (Biotin-Streptoavidin peroxidase complex method). Out of 185 autopsied cases, fifty-three cases had bacterial pneumonia. We performed the immunostaining to these 53 cases, of which 14 cases (26.4%) were diagnosed as pseudomonas pneumonia. All of the 14 cases had severe underlying diseases which were hematologic malignancies in six, solid malignancies in five and so on. Of ten of them pseudomonas pneumonia was considered to be the direct cause of death. P. aeruginosa was observed in alveolar space in all cases, and in bronchial and bronchiolar lumen in many cases. P. aeruginosa was also detected in alveolar and vascular walls. Histopathologically necrotizing vasculitis and alveolar destruction were characteristic, and intra-alveolar hemorrhage, fibrinous exudate, abscess formation, coagulation necrosis and thrombosis were observed in most cases. Necrotizing vasculitis and intra-alveolar hemorrhage were more severe in the cases of leukopenic patients.

Adult↗

[A case of adult T-cell leukemia with pulmonary cryptococcosis, cryptococcal meningitis and Pneumocystis carinii pneumonia].

A 66-year-old woman was admitted to the Medical College Hospital of Oita on February 23, 1988, because of headache and fever. Chest X-P and chest CT findings showed a coin lesion in r-S4. Cryptococcus neoformans was isolated from the CSF. Abnormal lymphocytes with lobulated nuclei were found in 0-5% of peripheral leukocytes. The ATLA-antibody was positive and bone marrow smear showed normal myelogram. According to these data, we diagnosed the patient as smouldering adult T-cell leukemia accompanied with pulmonary cryptococcosis and cryptococcal meningitis. C. neoformans disappeared from the CSF and cryptococcal antigen was not detectable after Amphotericin B and Flucytosine treatment. On April 1, the patient complained of a dry cough, high fever and dyspnea. A chest X-ray showed bilateral patchy infiltrations. By the methenamine silver staining, cysts of Pneumocystis carinii were found in the specimens of transbronchial lung biopsy and bronchoalveolar lavage fluid. The abnormal shadow on chest X-ray disappeared after TMP-SMX and aerosolised pentamidine treatment.

Aged↗

[A clinicopathological study on cytomegalovirus infection].

A clinicopathological study was carried out in 200 autopsied cases experienced in our department from 1981 to 1988. Cytomegalovirus infection was detected in 18 cases (9.0%). Eleven patients were male and 7 were female, and their ages ranged from 21 to 72 with a mean of 58.1 years. Primary diseases were mainly Non-Hodgkin's lymphoma (7 cases) and Adult T-cell leukemia (4 cases), and corticosteroid had been administered to all of them. The most commonly involved organ was lung (77.8%), followed by adrenal (55.6%), esophagus, pancreas, ovary (22.2%), stomach, small intestine, thyroid (16.7%), liver, kidney, tongue (11.1%), and so on. Concomitant infections were frequently complicated, which were bacterial pneumonia (5 cases), fungal pneumonia (3 cases), disseminated varicella-zoster infection (2 cases) and herpes simplex virus esophagitis or stomatitis (5 cases), while, ten patients died of cytomegalovirus pneumonia. Cytomegalovirus infection was one of the fatal opportunistic infections in immunocompromised, especially cell-mediated immunity impaired, hosts such as the patients with lymphocytic malignancies.

Adult↗