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Biomedical subjects

J Goto

Publications and source records attributed to J Goto.

At least 163 records · Page 9Linked to original sources

[A pathological study on herpes simplex virus infections in adults].

A pathological study was carried out in 200 autopsied cases experienced in our department from 1981 to 1988. Eight patients (4.0%) had herpes simplex virus (HSV) infections in their visceral organs. Another one patient was diagnosed as HSV hepatitis through necropsy of liver. The nine patients (five of them were male) ranged in age from 34 to 70 years (mean, 58). Four patients had non-Hodgkin's lymphoma, and the other included one with adult T-cell leukemia, one with multiple myeloma, one with idiopathic interstitial pneumonia and one with bronchial asthma, however, one did not have any underlying disease. Two patients died of HSV fulminant hepatitis and one died of HSV diffuse interstitial pneumonia. The most commonly involved organ was esophagus (7/8), followed by tongue (5/8), liver (3/9), spleen, pancreas, lymph node (2/8), and lung, adrenal, tonsil (1/8). Typical herpetic changes such as ballooning degeneration of cells, multinucleated giant cells, ground-glass nuclei and Cowdry type A intranuclear inclusions were observed at the margin of the ulcer or coagulation necrosis. Indirect immunoperoxidase stain revealed HSV-1 antigen in all of the 9 cases, HSV particles were demonstrated in 2. Seven patients had concomitant infections with one or more pathogens in addition to HSV, which included cytomegalovirus in 5, aspergillus in 4, candida in 3 and bacteria in 3.

Adult↗

Reductive biotransformation of 3-oxo bile acids in human blood.

7 alpha,12 alpha-Dihydroxy-3-oxo-5 beta-cholanoic acid labeled with 18O atoms was incubated with human blood, and the biotransformation products were separated and characterized by gas chromatography-mass spectrometry as the pentafluorobenzyl ester-trimethylsilyl and -dimethylethylsilyl ether derivatives. 3 beta,7 alpha,12 alpha-Trihydroxy-5 beta-cholanoic acid was identified as a main metabolite. When 3-oxo bile acid was incubated with human blood denatured at 70 degrees C for 2 min, no metabolites were formed. The enzymic reduction activity proved to be localized in the red blood cell fraction.

Bile Acids and Salts↗

Potential bile acid metabolites. XV. Synthesis of 4 beta-hydroxylated bile acids; unique bile acids in human fetal bile.

The 4 beta-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, and cholic acids were synthesized from their respective parent compounds. The principal reactions employed were 1) beta-face cis-dihydroxylation of delta 3 intermediates with osmium tetroxide-N-methylmorpholine N-oxide, 2) selective cathylation of vicinal 3 beta,4 beta-diols followed by oxidation of the resulting 4 beta-monocathylates, or direct selective oxidation at C-3 of 3 beta,4 beta-diols with pyridinium chlorochromate, and 3) stereoselective reduction of the 3-oxo compounds with tert-butylamine-borane complex. The results of analysis of the prepared 4 beta-hydroxylated bile acids with a diequatorial trans-glycol structure and their 3 beta-epimers by proton and carbon-13 nuclear magnetic resonance spectroscopies are briefly discussed along with the mass spectrometric properties.

Bile↗

Determination of 3 beta-hydroxylated bile acids in human serum and liver tissue.

3 beta, 7 alpha-Dihydroxy-5 beta-cholanoic acid (3 beta, 7 alpha-diOH) was detected in serum of 3 patients with intrahepatic cholestasis. 3 beta, 7 beta-dihydroxy-5 beta-cholanoic acid (3 beta, 7 beta-diOH) appeared in serum of those patients after treatment with ursodeoxycholic acid (UDC). These bile acids were also detected in only unconjugated fractions of serum of another 7 patients with chronic liver diseases, but not in liver tissue of them. The liver does not seem to from these bile acids itself because they were absent in liver tissue.

Bile Acids and Salts↗

[Silicosis and lung cancer].

A clinicopathological analysis was carried out on 50 cases of lung cancer with silicosis diagnosed from April 1975 to March 1988. All patients were males and the age distribution ranged from 47 to 85 years with a mean of 63.5 at diagnosis. They had been exposed to silica in tunneling for 3 to 42 years, with an average of 15.1. Forty eight cases smoked. Histologically, squamous cell carcinoma was the most common with 29 cases, followed by 10 small cell carcinomas, 6 adenocarcinomas, 4 large cell carcinomas and one adenosquamous carcinoma. Thirty seven tumors were located in peripheral regions, mostly upper lobe or S6, while 13 tumors were in large bronchi. As the most common histological types of lung cancer with silicosis were squamous cell carcinoma and small cell carcinoma, some carcinogens might be involved in tumorigenesis. Silica alone is not considered to be a carcinogen, however, silica containing adsorbed polycyclic aromatic hydrocarbons from cigarette smoking or from industrial pyrolysis can act as a carcinogen or promoter.

Adenocarcinoma↗

[Autonomic dysfunctions in acute intermittent porphyria].

A young woman with acute intermittent porphyria is described. She was admitted in a prolonged attack and had developed a flaccid quadriplegia. During the course she showed various manifestations of the autonomic nervous system, including pupils, gastrointestinal tract, cardiovascular system and others. On admission her pupils were equally mydriatic, and reacted to light sluggishly. Dilation of the pupils was seen when cocaine was instilled, but not when adrenalin. It was suggested that the parasympathetic control of pupils was disturbed. She complained repeatedly abdominal pain, nausea, vomiting, and constipation. However, diarrhea was rarely found. Radiological examinations revealed that her bowel movements were markedly impaired. Sinus tachycardia and elevation of blood pressure were frequently observed with attacks, and they correlated with the clinical course. With tachycardia the coefficient variance of R-R interval was markedly decreased, and large dose of atropine failed to accelerate the heart rate. These indicate that the vagal function was markedly impaired with attacks. The effects of isoproterenol and of propranolol on the heart rate were normal. Phenylephrine and phentolamine changed the blood pressure normally. From these it was concluded that the sympathetic nervous function was not so impaired at the time examined. However, with the elevation of blood pressure plasma and urinary noradrenaline were markedly increased. Other autonomic and related manifestations observed during the course included disorders of sweating, loss of sphincter control, fever of unknown cause and amenorrhea.

Acute Disease↗

[HTLV-I associated myelopathy (HAM) complicated with chronic polymyositis].

The patient was a 49-year-old woman. Since her age of 42, she noticed a proximal weakness of both legs. She also experienced pedal paresthesia and urinary frequency. Physical examination disclosed a diffuse goiter and bilateral Babinski sign. Results of EMG and muscle pathology were compatible with the diagnosis of polymyositis. Treatment with prednisolone improved muscle weakness, urinary difficulties and struma. 7 years later, HTLV-I antibody happened to be strongly positive both in serum and CSF. Then most of her neurological problems were attributed to HAM. However, recent studies of re-biopsy muscle specimens disclosed scattered necrotic fibers, phagocytosis and endomysial or perivascular infiltration of inflammatory cells. These infiltrating cells were classed mostly as helper/inducer T cells. These observations suggested the coexistence of polymyositis in the present case as well. So far, the combination of HAM and polymyositis has not been reported. It seems important to decide if HTLV-I could induce chronic polymyositis as in the case of HIV infections.

Chronic Disease↗

["AB-Triple V" therapy of relapsed or refractory acute myelogenous leukemia].

Sixteen adults with acute myelogenous leukemia (AML) in relapse or refractory to conventional therapy were treated with AB-Triple V therapy. This regimen consists of aclarubicin, behenoyl cytosine arabinoside, etoposide, vincristine, and vinblastine or vindesine. Patients who obtained complete remission (CR) were then given monthly three courses of AB-Triple V therapy, and further courses of AB-triple V therapy every three months. Eleven of the 16 patients entered CR, three were no response, and two died early after initial AB-Triple V therapy. Among 11 patients who achieved CR, 7 are alive and in CR during 1 to 13 months, one died of hepatic failure, and three patients died of infection in CR. Systemic arthralgia following the administration of vinblastine were frequently observed. These results indicate that this salvage therapy are useful relapsed or refractory AML. Therefore, the role of this combination chemotherapy as a part of the initial post-remission therapy needs to be evaluated.

Aclarubicin↗

Potential bile acid metabolites. 14. Hyocholic and muricholic acid stereoisomers.

The complete set of the eight theoretically possible stereoisomeric 3,6,7-trihydroxy-5 beta-cholanic acids, four of which are new, related to hyocholic and muricholic acids were prepared from chenodeoxycholic acid. The principal reactions used were 1) cis-dihydroxylation of delta 6-compounds with osmium tetroxide/N-methylmorpholine N-oxide; 2) trans-dihydroxylation of 6 alpha, 7 alpha-epoxy compounds with boron trifluoride etherate in N,N-dimethyl-formamide; 3) inversion of equatorial 3 alpha-hydroxylated compounds to the corresponding 3 beta-epimers with diethyl azodicarboxylate/triphenylphosphine/formic acid; and 4) stereoselective reduction of 7-keto derivatives with zinc borohydride (or sodium borohydride) and by metallic potassium/tert-amyl alcohol.

Bile Acids and Salts↗

Identification of 3 alpha,4 beta,7 alpha-trihydroxy-5 beta-cholanoic acid in human bile: reflection of a new pathway in bile acid metabolism in humans.

The chemical synthesis, nuclear magnetic resonance, and mass spectrometric characteristics of the first C-4 hydroxylated bile acid analogues are described. The data definitively confirm, for the first time, the identity of 3 alpha,4 beta,7 alpha-trihydroxy-5 beta-cholanoic acid in human fetal gallbladder bile. In addition, 3 alpha,4 beta,7 alpha-12 alpha-tetrahydroxy-5 beta-cholanoic was identified in the feces from healthy newborn infants many days after birth, indicating a hepatic origin for C-4 hydroxylation of bile acids. To our knowledge bile acids hydroxylated at the C-4 position of the steroid nucleus have never been previously recognized in any mammalian species. The finding of this novel bile acid which accounts for 5-15% of the total biliary bile acids in early gestation indicates that C-4 hydroxylation is a unique and important metabolic pathway in early human development.

Bile↗

The biotransformed metabolite profiles in blood after intravenous administration of dehydrocholic acid.

One gram of dehydrocholic acid was injected intravenously into two patients with percutaneous transhepatic cholangial drainage, and the biotransformed metabolites profiles over a 120-min period in serum and bile were analyzed. In serum unconjugated 3 alpha-hydroxy-7,12-dioxo-cholanoic acid (3 alpha-OH-7,12-OXO) acid was markedly increased after the injection of dehydrocholic acid, and reached about 80 microM within 30 min. On the other hand, conjugated 3 alpha, 7 alpha-dihydroxy-12-oxo-cholanoic acid (3 alpha,7 alpha-OH-12-OXO) was consecutively increased with lag time to an elevation of 3 alpha-OH-7,12-OXO. In bile, the major constituent of metabolites was conjugated 3 alpha,7 alpha-OH-12-OXO (more than 90% of the excreted metabolites), while conjugated 3 alpha-OH-7,12-OXO was detected as minor constituent. Therefore, between bile and serum, there was great difference in biotransformed metabolites profiles. The mechanism of elevation of unconjugated 3 alpha-OH-7,12-OXO in serum remains obscure, but this new finding raised a question as to whether organ-reducing 3-keto group of dehydrocholic acid is restricted to the liver.

Aged↗

Studies on steroids. CCXXXVIII. Determination of bile acids in liver tissue by gas chromatography-mass spectrometry with negative ion chemical ionization detection.

A method for the determination of bile acids in 2-10 mg of human liver tissue by gas chromatography (GC) in combination with negative ion chemical ionization (NICI) mass spectrometry is described. Unconjugated, glycine- and taurine-conjugated bile acids labelled with 18O and 2H were used as internal standards. The preparation of these compounds was attained by the exchange reaction of the carbonyl group with H218O, followed by metal hydride reduction. Bile acids in solubilized liver tissue 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 then derivatized to the pentafluorobenzyl ester-dimethylethylsilyl ethers. Subsequent resolution of each fraction into lithocholate, deoxycholate, chenodeoxycholate, ursodeoxycholate and cholate was attained by GC on a cross-linked 5% phenylmethyl silicone fused-silica capillary column where bile acids were monitored with a characteristic carboxylate anion [M - 181]-in the NICI mode using isobutane as a reagent gas. The newly developed method was applied to the quantitation of bile acids in liver tissue with satisfactory sensitivity and reliability.

Bile Acids and Salts↗

Studies on steroids. CCXXXIII. Separation and characterization of bile acid disulphates in human urine by high-performance liquid chromatography.

The separation of disulphates of cholate, chenodeoxycholate, deoxycholate and ursodeoxycholate and their glyco and tauro conjugates has been carried out by high-performance liquid chromatography (HPLC) on a reversed-phase column. The chromatographic behaviour of bile acid disulphates was dependent on the position of the sulphate and hydroxy groups and the structure of the side-chain. The method has been applied to the separation and characterization of disulphates in biological fluids without prior deconjugation. The disulphate fraction was obtained from a urine specimen by passing it through a Sep-Pak C18 cartridge, followed by group separation by ion-exchange chromatography on a lipophilic gel, piperidinohydroxypropyl-Sephadex LH-20. Subsequent resolution into individual disulphates was attained by HPLC on Radial-Pak A and Cosmosil 5C18 columns. Taurochenodeoxycholate 3,7-disulphate and taurodeoxycholate 3,12-disulphate in human urine were unequivocally identified on the basis of their behavior in HPLC using mobile phases of different pH.

Bile Acids and Salts↗