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The biological activities of benzo(a)pyrene, cyclopenta(c,d)pyrene, and 12 other structurally related compounds were assessed by mutagenicity studies with bacterial and mammalian cells and/or skin tumorigenicity studies with mice. The ability of the parent hydrocarbons to be metabolically activated to mutagenic products was examined in strains TA98 and TA100 of Salmonella typhimurium, using 3 experimental protocols. In each case, cyclopenta(c,d)pyrene was metabolically activated to products mutagenic to the bacteria to a greater extent than was benzo(a)pyrene. However, 7,8-dihydrobenzo(a)pyrene and 0,10-dihydrobenzo(e)pyrene were the best substrates for metabolic activation to bacterial mutagens. Highly purified epoxide hydrase added to a purified and reconstituted monooxygenase system readily abolished the mutagenic activity observed in strain TA100 of S. typhimurium when cyclopenta(c,d)pyrene was the substrate, but not when benzo(a)pyrene was the substrate. Inherent mutagenicity of several epoxides of the hydrocarbons generally paralleled the ability of their potential metabolic precursors to be activated to mutagens. 1-Pyrenyloxirane and 10,11-dihydrocycloheptapyrene 8,9-oxide were highly mutagenic in strains TA98 and TA100 of S. typhimurium, and in the former strain these activities were comparable to that observed with 9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, 4-Pyrenyloxirane was significantly less mutagenic than was 1-pyrenyloxirane in both strains of bacteria and in mammalian cells. Benzo(a)pyrene was over 20 times more tumorigenic than was cyclopenta-(c,d)pyrene, and it was the most potent of the 11 compounds tested for tumor-initiating activity in 2-stage initiation-promotion experiments on the skin of mice. Cyclopenta(c,d)pyrene had tumor-initiating activity comparable to that of benzo-(a)anthracene, but it was significantly less active than chrysene. Thus, contrary to inferences made from its high mutagenic activity, cyclopenta(c,d)pyrene is a weak tumor initiator on mouse skin.

Three synthetic oligodeoxynucleotides complementary to different parts of an RNA encoding a glycine receptor subunit were used to discriminate heterogenous mRNAs coding for glycine receptors in adult and neonatal rat spinal cord. Injection of the three antisense oligonucleotides into Xenopus oocytes specifically inhibited the expression of glycine receptors by adult spinal cord mRNA. In contrast, the antisense oligonucleotides were much less potent in inhibiting the expression of glycine receptors encoded by neonatal spinal cord mRNA. Northern blot analysis revealed that the oligonucleotides hybridized mostly to an adult cord transcript of approximately 10 kilobases in size. This band was also present in neonatal spinal cord mRNA but its density was about one-fourth of the adult cord message. There was no intense band in the low molecular weight position (approximately 2 kilobases), the existence of which was expected from electrophysiological studies with size-fractionated mRNA of neonatal spinal cord. Our results suggest that in the rat spinal cord there are at least three different types of mRNAs encoding functional strychnine-sensitive glycine receptors.

We report on an autopsy case of cholangiocarcinoma associated with Caroli's disease. A 38-year-old woman was admitted to our hospital suffering from epigastralgia. A diagnosis of Caroli's disease was made after CT, US, and ERCP testing. Because of diffuse intrahepatic bile duct dilatation, the patient was treated with antibioticus. In August 1985, her CA 19-9 level was 3,800 U/ml. This data suggested the development of a carcinoma secondary to Caroli's disease, but no tumor in the liver had been detected in the US and CT examinations. The patient died on February 1, 1986, of hepatorenal failure, approximately seven years after her first admission. An autopsy revealed diffuse dilatation of the intrahepatic bile duct (Caroli's disease) with a cholangiocarcinoma.

Hematological and clinical biochemistry values of two species of monkeys (Macaca mulatta and Macaca fascicularis) were measured by using auto-analyzers. WBC and RBC counts of M. fascicularis were high and Hb, MCV, MCH and MCHC values of M. fascicularis were low in comparison with those of M. mulatta. Albumin and creatinine levels of M. fascicularis were lower than those of M. mulatta. Total protein and A1P values of female M. fascicularis were higher than those of female M. mulatta. Differences between the sexes were observed in MCV, inorganic phosphorus, total protein, albumin and creatinine in M. mulatta, whereas in M. fascicularis, such differences were demonostrated as to creatinine, phospholipids and triglycerides.

(±)-7β,8α-Dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (diol epoxide-1) and (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (diol epoxide-2) are highly mutagenic diol epoxide diastereomers that are formed during metabolism of the carcinogen (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene. Remarkable stereoselectivity has been observed on metabolism of the optically pure (+)- and (−)-enantiomers of the dihydrodiol which are obtained by separation of the diastereomeric diesters with (−)-α-methoxy-α-trifluoromethylphenylacetic acid. The high stereoselectivity in the formation of diol epoxide-1 relative to diol epoxide-2 was observed with liver microsomes from 3-methylcholanthrene-treated rats and with a purified cytochrome P-448-containing monoxygenase system where the (−)-enantiomer produced a diol epoxide-2 to diol epoxide-1 ratio of 6 : 1 and the (+)-enantiomer produced a ratio of 1 : 22. Microsomes from control and phenobarbital-treated rats were less stereospecific in the metabolism of enantiomers of BP 7,8-dihydrodiol. The ratio of diol epoxide-2 to diol epoxide-1 formed from the (−)- and (+)-enantiomers with microsomes from control rats was 2 : 1 and 1 : 6, respectively. Both enantiomers of BP 7,8-dihydrodiol were also metabolized to a phenolic derivative, tentatively identified as 6,7,8-trihydroxy-7,8-dihydrobenzo[a]pyrene, which accounted for ∼30% of the total metabolites formed by microsomes from control and phenobarbital-pretreated rats whereas this metabolite represents ∼5% of the total metabolites with microsomes from 3-methylcholanthrene-treated rats. With benzo[a]pyrene as substrate, liver microsomes produced the 4,5-, 7,8- and 9,10-dihydrodiol with high optical purity (>85%), and diol epoxides were also formed. Most of the optical activity in the BP 7,8-dihydrodiol was due to metabolism by the monoxygenase system rather than by epoxide hydrase, since hydration of (±)-benzo[a]pyrene 7,8-oxide by liver microsomes produced dihydrodiol which was only 8% optically pure. Thus, the stereospecificity of both the monoxygenase system and, to a lesser extent, epoxide hydrase plays important roles in the metabolic activation of benzo[a]pyrene to carcinogens and mutagens.

A 67-year-old male, who had a left hepatectomy for hepatocellular carcinoma, was readmitted to our hospital because of a left hemiparesis. A brain computed tomography scan and an r-carotid angiogram revealed a large mass involving the right parietal area, and thus a brain tumor removal was performed. A histological diagnosis of the removed brain tumor found it to be a metastatic, hepatocellular carcinoma. The patient died of pulmonary congestion due to lung metastasis, approximately 2 years and seven months after hepatectomy, and 1 year and three months after the removal of this metastatic brain tumor. In selected cases, the removal of a metastatic brain tumor seems to bring about improvements in the quality and duration of life.

In order to obtain a three-dimensional ultrasonogram as a first step for a general visualizing diagnosis, a new computerized ultrasonography was tried with patients from our obstetric and gynecological department, with the following results: 1. Time required: Collection of data for the three-dimensional part measuring 17 X 17 X 8.5cm took 17 seconds (Scanning time), and formation of the 32-image longitudinal sections and coronal sections (C-mode) took 46 seconds and 1 minute 54 seconds, respectively. Formation of the 64-image longitudinal sections and coronal sections (C-mode) took 1 minute 20 seconds and 3 minutes 20 seconds, respectively. 2. Images: The recorded and reproduced images were identical to the originals macroscopically and even as indicated on the line printer. The coronal images (C-mode) and the longitudinal images could well stand practical use. 3. Reproduction of images: All data were stored on magnetic tape which could be processed as needed. 4.(a) In obstetric patients, the images enabled us to confirm the location and expansion of the placenta and fetus more clearly. (b) In gynecological patients, it proved to be easy to get a whole view permitting better comprehension of the tumor shape, its internal components and its relation with the surrounding organs in a three-dimensional way.

In view of the paucity of reports describing symptoms of increased degree, and deterioration of left ventricular systolic function in patients with apical hypertrophic cardiomyopathy (apical HCM), two cases with congestive heart failure and progressive thinning of previously hypertrophied apical portions of the left ventricle are reported. These were among 13 patients observed from eight to 10 years. Case 1: A 56-year-old man was diagnosed as having apical HCM at the age of 49 years. Severe left ventricular hypertrophy and prominent ST-T changes were observed on ECG during his first admission. His left ventricular end-diastolic pressure (LVEDP) was 24 mmHg and a left ventriculo-gram revealed a decrease in the left ventricular cavity in the apex and marked hypertrophy of the apical wall. Moderate interstitial fibrosis without hypertrophy or disarray of myocytes was observed in a left ventricular endomyocardial biopsy specimen. In two episodes of cardiac arrest he was successfully resuscitated at the age of 50 years. At the age of 55 years, two-dimensional echocardiography revealed thinning and abnormal motion in the apical wall, and a defect in 201T1 accumulation was observed in the same region by perfusion scintigraphy. This patient was readmitted with a diagnosis of cerebral embolism at the age of 56 years. Cardiac catheterization revealed normal LVEDP (8 mmHg), and a left ventriculogram revealed an aneurysm in the left ventricular apex with normal major epicardial coronary arteries. He has been under treatment with antiarrhythmic medications, calcium antagonists and anticoagulants, and has become relatively asymptomatic. Case 2: A 69-year-old-man was diagnosed as having apical HCM after a complete evaluation, including cardiac catheterization, at the age of 59 years. His LVEDP was elevated (17 mmHg), and a left ventricular angiogram revealed marked hypertrophy localized to the apex. Ejection fraction was 64%. A left ventricular endomyocardial biopsy revealed interstitial fibrosis without hypertrophy of myocytes. Thereafter, he has been followed as a New York Heart Association functional class III to IV with occasional elevation of cardiac enzymes but without chest pain or acute changes in his ECGs. However, atrial fibrillation with complete right bundle branch block developed at the age of 60 years. Apical wall thinning and dyskinesis were diagnosed by 2D echocardiography and a defect in the 201T1 accumulation was observed at about 65 years of age. He was readmitted in severe cardiac failure at the age of 69 years, and he was diagnosed as having cardiac asthma with pulmonary capillary wedge pressure of 35 mmHg.(ABSTRACT TRUNCATED AT 400 WORDS)

This study describes the efficacy of the right gastroepiploic artery (GEA) as graft material for coronary artery bypass grafting (CABG) as assessed by exercise thallium 201 myocardial scintigraphy in eight patients (age, 59.4 +/- 9.35 years [mean +/- SD]) who underwent CABG with the GEA graft in the past 2 years. Planar and single-photon-emission computed tomographic (SPECT) images were obtained during and 3 hours after exercise. Planar images were evaluated quantitatively with the percentile-washout method, and SPECT images were evaluated qualitatively with a bull's-eye, polar-coordinate map. All patients had triple-vessel disease, and in situ GEAs were anastomosed to the right coronary artery in seven patients and to the left anterior descending coronary artery in one. The internal mammary artery graft was concomitantly used in all patients. The mean number of grafts per patient was 3.0 (range, 2-4). Preoperative exercise testing could not be performed in two patients because of emergency operation. By qualitative assessment with the polar-coordinate map, four patients showed improvement, one did not show any change, and one became worse due to perioperative myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Optically pure (+)- and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrenes [(+)- and (-)-BP 7,8-dihydrodiol] were tested for carcinogenicity by giving newborn mice i.p. injections of 20, 40, and 80 nmol of compound on Days 1, 8, and 15 of life. The animals were killed at 17 weeks of age. Control mice had 0.10 pulmonary adenoma per mouse, whereas animals treated with (+)-BP 7,8-dihydrodiol and (-)-BP 7,8-dihydrodiol had 0.16 and 9.28 pulmonary adenomas per mouse, respectively. When a 5-fold higher dose was administered according to the above dosage schedule, (+)-dihydrodiol caused 2.34 pulmonary adenomas per mouse and (-)-BP 7,8-dihydrodiol caused 32.2 pulmonary adenomas per mouse. When 200, 400, and 800 nmol of benzo(a)pyrene or (+)-BP 7,8-dihydrodiol were administered sequentially on Days 1, 8, and 15 of life, 4.13 and 18.5 pulmonary adenomas per mouse, respectively, were observed when the mice were 17 weeks of age. This high dose of (-)-BP 7,8-dihydrodiol killed most of the mice. Administration of (-)-BP 7,8-dihydrodiol caused a high incidence of malignant lymphomas, whereas (+)-BP 7,8-dihydrodiol and benzo(a)pyrene had little or no ability to cause malignant lymphomas.

The hypothesis that substance P (SP) might be a transmitter of primary sensory neurons was first proposed by Lembeck in 1953. A large amount of evidence supporting this hypothesis has recently accumulated, particularly since the elucidation of the chemical structure of SP by Leeman and her colleagues in 1971, which made a number of new approaches possible (e.g. radioimmunoassay for SP, immunohistochemistry and electrophysiological tests of SP action on central and peripheral neurons). SP is concentrated in certain primary afferent terminals in the spinal cord, is released therefrom when the dorsal roots are electrically stimulated, and exerts a powerful excitant action on spinal neurons. It is therefore likely that SP produces excitatory postsynaptic potentials (EPSPs) in spinal neurons, although the characteristics of SP-mediated EPSPs, i.e. their time course, ionic mechanisms, etc., remain to be revealed. Recent electrophysiological and neurochemical studies on the prevertebral ganglia of the guinea-pig strongly suggest that SP is released from axon collaterals of visceral primary afferent neurons in the ganglia and serves as a transmitter that generates non-cholinergic slow EPSPs in principal cells. There is evidence that this SP-mediated synaptic transmission in the sympathetic ganglia is under the influence of enkephalinergic presynaptic inhibition. Some preliminary experiments on the interaction between SP and enkephalins in the spinal cord are described.

Changing values of the pH in natural sediment-water systems did not affect the total amount of methylmercury generated in the sediments. However, partition of methylmercury between water and sediment did change, the amount of methylmercury in the water column doubling for a decrease in pH of 1.0 (sand) to 2.0 (organic sediment) units. This change is enough to explain, quantitatively, the observed elevations in mercury levels in fish taken from lakes of low pH.

A 69 year-old male was admitted to our hospital with early gastric carcinoma (Type IIc) and two macroscopic submucosal tumors. He had suffered from gastroduodenal ulcer for about forty years; postoperative histologic examination revealed the gastric ectopic glands to be a paracancerous lesion.

Two patients aged 2 months and 9 days with postoperative mediastinal infection were treated by continuous closed irrigation with 0.5% povidone-iodine solution. Satisfactory eradication was achieved in both two patients. Although serum iodine level was elevated as high as 7,610 micrograms/dl in the neonatal patient, no disturbances of the thyroid function and the acid-base balance were seen. The usefulness of continuous closed irrigation in the neonatal or infantile period was suggested.