Effects of N-(2-ethylhexyl)-3-hydroxybutyramide hydrogen succinate on the metabolisms of monoamines in the rat brain

N-(2-Ethylhexyl)-3-hydroxybutyramide hydrogen succinate (M-2H) has been reported to increase REM sleep. The effects of M-2H on the metabolisms of monoamines which have been implicated in the regulation of the sleep-wakefulness cycle were studied in rats. M-2H (500 mg/kg p.o.) increased the levels of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid and 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in various regions of the rat brain. However, no appreciable changes occurred in levels of serotonin (5-HT), norepinephrine, dopamine, or 3,4-dihydroxyphenylacetic acid. The effect of M-2H (500 mg/kg p.o.) on 5-HT metabolism was investigated with intraventricularly-injected [14C]-5-HT. Although [14C]-5-HT level was not significantly changed, [14C]-5-HIAA level was above control level in four brain regions such as the hypothalamus, hippocampus, midbrain and pons-medulla at 3 h after the administration of M-2H. M-2H retarded the efflux of intraventricularly-injected [14C]-5-HIAA in all brain regions except the cortex. These results suggest that M-2H preferentially impaired the transport system for acid metabolites of monoamines, resulting in increase of monoamine metabolite levels in the brain.     

In vivo activity and metabolic fate of 2-(2,3,3-triiodoallyl)tetrazole (ME1401), a novel antifungal agent

2-(2,3,3-Triiodoallyl)tetrazole (ME1401), a novel antifungal agent, showed therapeutic effectiveness in topical treatment of experimental dermal infections with Trichophyton mentagrophytes and Candida albicans in guinea-pigs. Addition of diethyl sebacate to the ME1401 preparations increased its in vivo antifungal activity and its penetration into the skin. When the estimation of efficacy of treatment with active formulations was made on the basis of skin lesion and the rate of negative skin cultures in comparison with those for infected, untreated or placebo-treated controls, the in vivo activity of 0.5% ethanol tincture or gel of ME1401 was comparable to that of reference antimycotic drugs such as clotrimazole, haloprogin and others. Pharmacokinetic studies in the experimental animals demonstrated that ME1401 was unstable in vivo, being readily converted to an active metabolite 2-(3-iodopropargyl)tetrazole (CN144) first and then to 2-propargyltetrazole (CN151). CN144 showed potent in vitro and in vivo antifungal activities, while the in vitro activity of CN151 was negligible.     

A case of metastatic optic nerve head and retinal carcinoma with vitreous seeds

Metastasis directly to the optic nerve head without choroidal involvement is rare. We report a case of metastatic adenocarcinoma of the optic nerve head and retina with vitreous seeds which was observed in a 45-year-old Japanese male. The primary site of the lesion was clinically the upper lobe of the left lung. Tumor emboli were observed in the central retinal vein. Vitreous seeds appeared to have arisen from a necrotic area and papillary projections of the tumor.     

Anterior and posterior association cortex contributions to the somatosensory P300

A P300 (P3)-evoked response is generated in a variety of mammalian species upon detection of significant environmental events. The P3 component has been proposed to index a neural system involved in attention and memory capacity. We investigated the contribution of anterior and posterior association cortex to somatosensory P3 generation. Somatosensory event-related potentials (ERPs) were recorded in controls (n = 10) and patients with unilateral lesions in temporal-parietal junction (n = 8), lateral parietal cortex (n = 8), or dorsolateral frontal cortex (n = 10). Subjects pressed a button to mechanical taps of the fifth finger (targets; p = 0.12), randomly interposed in sequences of taps to the second (standards; p = 0.76) and the third or fourth finger (tactile novels; p = 0.06). Occasional shock stimuli were delivered to the wrist (shock novels; p = 0.06). The scalp-recorded P3 was differentially affected by anterior and posterior association cortex lesions. Subjects with temporal-parietal lesions showed markedly reduced P3s to all types of stimuli at all scalp locations. The reductions were largest at the parietal electrode site over the lesioned hemisphere. Parietal patients had normal P3s for all stimulus types except for contralateral shock novels, which generated reduced P3s. Frontal lesions had reductions of the novelty P3 over frontal sites with minimal changes in the target P3. The data support the existence of multiple intracranial P3 sources. The data further indicate that association cortex in the temporal-parietal junction is critical for generating the scalp-recorded target and novelty P3s, whereas dorsolateral frontal cortex contributes preferentially to novelty P3 generation. The N2 component was reduced by parietal and frontal lesions in patients who had intact target P3s, suggesting that different neural systems underlie N2 and P3 generation.     

Morphometrical analysis of nuclear abnormality of tubular tumors of the stomach with image processing.

Nuclear size and shape on histological specimens were used to quantify nuclear abnormality in gastric tubular tumors. A valid technique for this morphometrical analysis by image processing was developed. Furthermore, the present study examined the nuclear size and shape to determine if they were reliable criteria to be used for differential diagnosis. Nuclear area, maximum diameter and maximum width on the histological specimens were defined as factors to represent nuclear size. Nuclear aspect ratio represented nuclear shape. Histological features revealed varied degrees of condensation of nuclei; this was due to different protocols for preparing the histological specimens. This finding indicated that the size of intermediate lymphocytes on the same specimens should be measured as a control in order to estimate the degree of nuclear condensation. The present study also demonstrated that at least 200 nuclei should be measured on the histological specimens to obtain accurate nuclear size and shape. Histologically, the nuclei in benign tubular adenoma and borderline lesions tended to be spindle-shaped, while those in well-differentiated type tubular adenocarcinoma tended to be round and swollen. The nuclei in borderline lesions were larger than those in benign tubular adenoma and smaller than those in well-differentiated type tubular adenocarcinoma. Our results for the above 4 factors corresponded well with these histological findings. The nuclear size and shape on histological specimens were concluded to be reliable criteria for assessing nuclear abnormality in gastric tubular tumors and useful ones for differential diagnosis.     

Malignant fibrous histiocytoma arising from a calcifying enchondroma – a case report

Summary. A man, 79 years of age, developed a malignant fibrous histiocytoma which arose in relation to a calcifying enchondroma of the distal femur. Radiographs showed a fracture through an intensely calcified bony tumour with no bony destruction. The clinical diagnosis was a dedifferentiated chondrosarcoma. Histology showed an anaplastic sarcoma with calcified tissue showing extensive areas of necrosis and degeneration. No chondrosarcomatous foci were found.

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Resumé. Nous rapportons le cas d’un homme de 79 ans, qui a développé un histiocytofibrome malin à partir d’un enchodrome calcifié du fémur distal. L’examen radiologique a montré une fracture au sein d’une tumeur très calcifiée sans association de destruction osseuse. Cette lésion apparaissait cliniquement être un chondrosarcome dédifférencié. Mais l’étude histologique a montré un sarcome anaplasique avec un tissu cartilagineux calcifié présentant des plages étendues de nécrose et de dégénérescence. Il n’y avait pas de foyer chondrosarcomateux visible.

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Accepted: 9 November 1996     

Tubular adenoma of the gallbladder with squamoid spindle cell metaplasia. Report of three cases with immunohistochemical study.

Three cases of tubular adenoma of the gallbladder with squamoid spindle cell metaplasia are reported. Two of the three patients, who were middle-aged Japanese, had a solitary polyp in the gallbladder, and the other had three polyps. All the lesions were detected incidentally by ultrasonography. The polyps were pedunculated with a fine or frail stalk, and ranged from 0.5 to 3.9 cm in diameter. Histologically, they were tubular adenomas accompanied by scattered foci composed of a compact collection of short-spindle or oval cells with mild atypia. These cells did not retain intercellular bridges, and lacked intracellular keratinization. Immunohistochemically, the spindle cells stained positively for high-molecular-weight cytokeratin (EAB 903, a marker of squamous cell differentiation), whereas adenoma cells lining the tubules were negative for this antigen. Therefore, the spindle cell component is considered to represent squamoid metaplasia of adenoma cells.     

Expression of the cell surface antigen detected by the monoclonal antibody A7 in pancreatic carcinoma cell lines

In a previous study, we used a murine monoclonal antibody, A7, against human colon carcinoma as a drug-carrier to treat colorectal cancer.¹ In the present study, we found that MAb A7 also reacted immunohistochemically with 73% of human pancreatic carcinoma cell lines, with the A7 antigen mainly being detected on the cell surface. However, the A7 antigen was found in only 9% of the spent media of these human pancreatic carcinoma cell lines by ELISA. On the other hand, the positive incidence of CA19-9, POA, ferritin, CEA, DU-PAN-2 and SLX in those spent media was 100%, 64%, 64%, 55%, 55% and 36%, respectively. These results suggest that the A7 antigen may only rarely be shed into the sera of pancreatic cancer patients, in which case MAb A7 could be a suitable drug-carrier in targeting chemotherapy for pancreatic cancer patients.     

Bilateral subclavian steal associated with severe coarctation of the thoracic aorta and an aberrant right subclavian artery

A 10-year-old girl having bilateral subclavian steal associated with severe coarctation of the thoracic aorta and an aberrant right subclavian artery was found, on admission, to have no difference between upper and lower extremity blood pressure, but echocardiography revealed severe thoracic aorta coarctation and systolic blood pressure in the carotid arteries exceeding 200 mmHg estimated by Doppler ultrasonography. Magnetic resonance imaging and angiography demonstrated bilateral subclavian steal without esophageal compression. We reconstructed the aortic arch using the left subclavian artery and a reversed Blalock-Park procedure, then repaired the coarctation with a 14 mm woven double velor vascular graft. The girl was symptom-free following uncomplicated recovery from surgery. Doppler ultrasonography 2 weeks after surgery showed the pressure gradient across the aortic arch had decreased from 180 mmHg to 60 mmHg. This residual gradient at the anastomosis between the ascending aorta and left subclavian artery may improve as native vessels grow.