Studies on the synthesis of antiulcer agents. VI. Synthesis and antiulcer activity of dihydrobenzofuranone derivatives

The derivatives (2) of 3-(2,3-dihydro-2,2-dimethyl-3-oxo-5-benzofuranyl) acrylic acid (2b) were synthesized. The compounds (3a-g) in which bromo, methoxy, nitro, amino or acetamido group was introduced on the benzene ring of the derivatives (2) and the compounds (3h-k) in which acryloyl moiety was introduced on the 6- or 7-position of the benzofuranone skeleton also synthesized. Furthermore, propionic acid derivatives (4a-c), acetic acid derivatives (4d-g), formic acid derivatives (4h-k) and oxyacetic acid derivatives (5) were prepared by converting the acryloyl moiety of the derivatives (2) into propionyl, acetyl, formyl and oxyacetyl groups. These compounds were tested for antiulcer activities. Among these compounds, 1-[3-(2,3-dihydro-2,2-dimethyl-3-oxo-5-benzofuranyl)acryloyl]piperidine (2d) and 4-[3-(2,3-dihydro-2,2-dimethyl-3-oxo-5-benzofuranyl)acryloyl] morpholine (2g) were found to have stronger antiulcer activities.     

Two cases of acute disseminated encephalomyelitis with lesions in the thalamus or basal ganglia on MRI]

Lesions in the thalamus or basal ganglia have rarely been reported in acute disseminated encephalomyelitis (ADEM). We experienced 2 cases of ADEM, in which MRI showed lesions in the thalamus or basal ganglia. Case 1, a 4-year-old boy, had gait disturbance, hyperesthesia and hyperreflexia. MRI (T2 weighted image) showed multiple high intensity areas in the right frontal lobe, bilateral parietal lobes and bilateral thalami. Case 2, a 4-year-old girl, complained of gait disturbance following a febrile episode, and displayed hyperreflexia. Several days later, she had visual disturbance of the left eye. MRI (T2 weighted image) revealed multiple high intensity areas in the dentate nucleus of left cerebellum, left occipital lobe, bilateral caudate nuclei, and the anterior part of bilateral lenticular nuclei. In both cases, CT could not demonstrate these lesions. Both of them were treated with corticosteroid and recovered rapidly. They had no recurrence. MRI is useful in diagnosis and follow-up of ADEM and may reveal lesions other than cerebral or cerebellar white matters.     

Ethylene vinylacetate copolymer particles dissolved in polyvinyl alcohol (2,000-mer) solution as an embolic material for vascular anomalies

We have prepared a new material for embolisation: ethylene vinylacetate copolymer dissolved in polyvinyl alcohol. When in contact with blood, polyvinyl alcohol rapidly becomes a soft gel, which is accompanied by wedging of the ethylene vinylacetate copolymer. We analysed the histopathology of intra-arterial microemboli in rats, after intracarotid injection of this material. We confirmed that it was applicable to embolisation for neurosurgical treatment.     

Distribution of radiolabeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitros ourea hydrochloride in rat brain tumor: intraarterial versus intravenous administration

To assess the rationale of intraarterial (i.a.) 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy, distribution of 14C-labeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)- 3-nitrosourea in rat glioma was studied after i.a. or i.v. infusion. Immediately after infusion, the tumor located in the hemisphere of intracarotid infusion received 4.6-fold higher radioactivity than the tumor located contralaterally to intracarotid infusion and 2.8-fold higher radioactivity than i.v. infusion. The difference was kept up to 30 min after i.a. infusion. Autoradiographic observation indicated rather uniform distribution of the tracer in the central portion of i.a. infusion. However, in the periphery of i.a. infusion, distribution of the tracer was nonhomogenous. The results indicate that i.a. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy is useful when the tumor has high blood flow and is located in the center of an infused area.     

The morphological and biochemical changes in skeletal muscle fibers by dietary protein restriction.

The effects of dietary protein restriction on skeletal muscle fibers were studied according to morphological and biochemical approaches. Protein and DNA content of quadriceps muscles from young adult rats were decreased by the low protein and protein-free diet. Morphological examination demonstrated that there was a significant decrease in the size of muscle fibers without change in their numbers due to protein restriction. The protein/DNA ratio, accepted as an index of cell size in biochemical approaches, was compared with cell size on photomicrographs. Actual fiber size appeared much smaller than that indicated by the protein/DNA ratio.     

Molecular biological study of the rhodopsin gene in Japanese patients with autosomal dominant retinitis pigmentosa]

The author analyzed codon 347 of the rhodopsin gene using PCR (polymerase chain reaction) amplification and restriction enzymes in 19 unrelated Japanese families including 28 patients with autosomal dominant retinitis pigmentosa (ADRP). An allele of codon 347 mutation was found in a family (father and daughter). Sequence analysis shows that the mutation is from CCG to CTG. This mutation appears to be the cause of one form of ADRP, since it was also found in Japanese cases of ADRP which have a different racial background from families reported by Dryja et al.     

Interventional embolization with fibrin glue for a large inferior mesenteric-caval shunt.

We report an unusual case of a large inferior mesenteric-caval shunt in a 25-year-old man without cirrhosis with hypoproteinemia and hypochromic anemia. In this large shunt the direct communication was between the inferior mesenteric vein and the internal iliac vein. Hemodynamic change as a result of the shunt was thought to cause his present clinical problems and future portosystemic encephalopathy. Percutaneous transcatheter embolization of the shunt with fibrin glue was performed through the internal iliac vein, and this offered amelioration of hypoproteinemia and reduction of serum ammonia levels without any complications. An interventional radiologic approach instead of surgical ligation should be attempted for portosystemic shunts, and fibrin glue, as well as coils or a detachable balloon, is also valuable as an embolizing material.     

Hypogonadism of male prolactinomas: Relation to pulsatile secretion of LH: Hypogonadisms des Mannes mit Prolaktinomen: Beziehungen zur pulsatilen LH-Sekretion

In order to investigate whether a hypothalamic disorder cause hypogonadism in male prolactinomas, LH pulsatile secretion was studied in 13 male patients. Serum PRL levels ranged from 186 to 45,000 ng ml-1 before treatment, and all the tumors were macroadenomas. Reduced LH secretion was revealed in 5 of 13 patients, and FSH was reduced in 1 of 13. Serum testosterone (T) levels were lower than the normal limit in all the patients. HCG tests in 3 patients showed good responses, but the peak values of T were lower than those of normal men. LH pulsatilities were examined in 5 hyperprolactinemic patients before treatment, in 4 hyperprolactinemic patients after operation, and in 8 normoprolactinemic patients after operation and/or bromocriptine treatment. There was no significant difference of the mean LH values, the frequencies of LH pulses, and amplitudes among the hyperprolactinemic patients before operation (n = 5), the normoprolactinemic patients after operation (n = 8), and normal men (n = 7). From these results, it was evident that the hypothalamus and pituitary function of male prolactinomas were well preserved, in spite of higher serum PRL levels and larger tumor size than those reported in females. It is suggested that the main cause of hypogonadism in these patients is due to testicular dysfunction resulting from excessive serum PRL.     

A case of progressive muscular dystrophy with numerous arterioluminal vessels

A 48-year-old man had histologically demonstrated cardiac involvement associated with progressive muscular dystrophy. On coronary arteriography, numerous vascular communications between the coronary arteries and the left ventricular chamber were found. These vascular communications are considered to be the arterioluminal vessels. This is the first report of a case of progressive muscular dystrophy with numerous arterioluminal vessels.     

Study on local recurrence of squamous cell carcinoma of the lung on hilar lesion

The study population consisted of 62 patients with squamous cell carcinoma of the lung on hilar lesion who underwent curative or relative curative resection during the seven year period between January, 1980 and December, 1986. We studied the correlation between local recurrence and the distance from the surgical margin of the trachea or bronchus to the tumor. 1) As the classification of the T and N factors increased, the incidence of local recurrence became higher. 2) In order to prevent local relapse, we need to completely resect the hilar and mediastinal lymph nodes, and we must maintain a distance of 16 mm or more between the surgical margin of the trachea or bronchus and the tumor.