Effect of S-8666 on Cl- transport in the rabbit connecting tubule perfused in vitro.

S-8666, [6, 7-dichloro-5-(N, N-dimethylsulfamoyl)-2, 3-dihydrobenzofurancarboxylic acid] is a potent diuretic with uricosuric action. Although the major site of action of S-8666 has been proven by the in vitro microperfusion study to be the thick ascending limb of Henle's loop, clearance studies in the rat suggested that this drug has an additional thiazide-like action. To provide direct evidence that S-8666 acts also on distal nephron segments, we examined effect of S-8666 on Cl- flux across the rabbit connecting tubule perfused in vitro. The drug suppressed the lumen-to-bath Cl- flux by 96 +/- 41 (S.E.)pmol.mm-1.min-1 (n = 9) without affecting transmural voltage. To demonstrate that S-8666 acts on the connecting tubule cell, the target of thiazide diuretics, we compared effects of S-8666 and trichlormethiazide on the basolateral membrane voltage of the connecting tubule cell. Both drugs added to the lumen caused a small but significant hyperpolarization of the basolateral membrane without affecting transmural voltage. We conclude that S-8666 is a unique uricosuric diuretic having actions on both thick ascending limb of Henle's loop and connecting tubule.     

A CASE OF EARLY GASTRIC CANCER ACCOMPANIED BY DIEULAFOY ULCER IN A YOUNG WOMAN

A case of early gastric carcinoma accompanied by Dieulafoy ulcer is presented. The patient, a 26‐year‐old female, visited our emergency room with chief complaints of massive hematemesis and tarry stool. The initial endoscopic examination revealed a superficial depressed lesion with a faded color accompanied by a tiny ulcer with converging folds at the anterior wall of the middle gastric body. Although no active bleeding vessel was found at that time, the patient was admitted to our hospital for further check‐ups and treatment. On the 6th hospital day, she developed massive hematemesis resulting in shock. Urgent endoscopy, this time, disclosed an exposed bleeding vessel at the small ulcer floor previously mentioned, and endoscopic hemostasis was achieved. Since, however, a biopsy at initial examination from the surrounding depressed area proved carcinoma, a partial distal gastrectomy was subsequently carried out. Histological examination of the resected specimen confirmed the diagnosis of carcinoma limited to the mucosa and submucosa along with findings consistent with Dieulafoy ulcer. This is a rare case of combination of early cancer and Dieulafoy ulcer particularly in such a young patient. A review of the literature is also presented.     

Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy

We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease.     

Extremely Well Differentiated Papillary Adenocarcinoma of the Lung with Prominent Cilia Formation

We describe a 54-year-old woman with primary pulmonary adenocarcinoma showing a characteristic papillary architecture and prominent cilia formation. Immunohistochemically, the tumor cells were positive for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and Leu Ml, and negative for lactoferrin and surfactant apoprotein. An ultrastructural study also indicated differentiation toward bronchial surface epithelial cells. To our knowledge, this type of neoplasm has not been reported as peripheral-type adenocarcinoma of the lung. Acta Pathol Jpn 42: 745–750, 1992.     

N10 potential as an antidromic motor evoked potential in a median nerve short-latency somatosensory evoked potential study.

When stimulating the mixed nerve to record evoked potential, both sensory and motor fibers are activated before entering the spinal cord. The N10 potential has been described as an antidromic motor evoked potential based on results obtained by recording at the anterior midneck. In the present study, we examined the changes in latencies of Erb's potential, N10, and N13 by stimulating the median nerve distally at the wrist and proximally at the elbow. The conduction velocity of N10 calculated by the difference between N10 latencies at the two stimulation points was consistent with motor conduction velocity, although N13 conduction velocity estimated by the same method reflected a sensory conduction velocity. A positive relation was also observed between the indirect latency from the stimulation point to the anterior root as calculated using the equation (F - M - 1) / 2 (ms) and the direct latency to the negative peak of the N10 potential. Our data support the notion that N10 represents antidromic motor potential originating in the spinal entry zone of the anterior root.     

A case of antiphospholipid syndrome associated with left subclavian artery thrombosis and left external iliac vein thrombosis]

Arterial thrombosis is one of the major symptoms of antiphospholipid syndrome (APS). However, thrombosis in a primary branch of the aorta has rarely been reported in APS. We report here a case of APS complicated by thromboses in both the left subclavian artery and the left external iliac vein. A 32-year-old woman was admitted in May, 1990 complaining of no pulse in the left superficial arteries (e.g., left radial artery) for the past 5 years and acute swelling of the left lower extremity. A left ascending phlebography showed an occlusion of the external iliac vein and arteriography revealed obstruction in the left subclavian artery. Collateral circulations were developed at the site of each thrombus. Clotting and immunological studies revealed a prolonged APTT, a high titer of anticardiolipin antibody and lupus anticoagulant positive. We ruled out various diseases and clinical risk factors predisposing to both arterial and venous thromboses. Accordingly, we concluded that both thromboses were based on APS. Following treatment with anticoagulants, aspirin and corticosteroid, the swelling of her left thigh was diminished and the antibody titer was decreased within 3 months.     

Spontaneous subcapsular hepatic hemorrhage associated with pregnancy: Report of a case

We report herein a case of spontaneous subcapsular hepatic hemorrhage which occurred in a 33-year-old woman 1 day after she had been delivered of her second child by cesarean section following an uneventful pregnancy. She complained of right upper quadrant pain on the 1st postoperative day, and computed tomography (CT) showed subcapsular low-density masses in both liver lobes, while extravasation was demonstrated by CO₂ intraarterial digital subtraction angiography (IADSA). The hemorrhage was successfully controlled by transcatheter arterial embolization (TAE). However, on the 3rd day after TAE, an exploratory laparotomy was performed to establish an exact diagnosis to explain the persistent abdominal pain and abnormal liver function tests. Subcapsular hematomas in both lobes were confirmed and no visible laceration was present. The patient recovered gradually by spontaneous absorption of the hematomas and was discharged on the 22nd postoperative day. Spontaneous hepatic hemorrhage associated with pregnancy is a very rare complication, and establishing a correct diagnosis and initiating appropriate therapy are essential for this life-threatening disease.     

Temporal and spatial expression of transforming growth factor-β in the healing patellar ligament of the rat

We investigated the temporal and spatial expression of transforming growth factor-β in the healing patellar ligament of the rat by immunohistochemistry. The mid-portion of the medial half of the patellar ligament in 14-week-old male Wistar rats was cut transversely with a scalpel. On day 1 after ligament injury, diffuse staining for transforming growth factor-β was observed in the extracellular matrix filling the wound, and the staining in the adjacent ligament tissue was as weak as it was in the normal ligament. On day 3, the intensity of the diffuse extracellular staining decreased, and the staining was observed in correspondence with the cellular distribution in the wound site and in the adjacent uninjured ligament tissue. On day 7, the intense staining was widely distributed over the whole length of the ligament tissue. On day 28, the staining for transforming growth factor-β was still observed at the wound site and in the adjacent uninjured ligament tissue, where the staining was reduced in intensity but still stronger than it was in the normal ligament. On day 56, the expression of transforming growth factor-β was still detectable at the wound site: however, in the adjacent uninjured ligament tissue, it had almost subsided to the normal level. The results of the present study suggest that ligament healing may be accompanied by extensive changes in the expression of transforming growth factor-β over the whole length of ligament tissue.     

-Hydroperoxy diethyl peroxide, an unusual natural compound isolated from an ascidian (Phallusia mammillata): acute toxicity in DDY mice

-Hydroperoxy diethyl peroxide, a novel compound found in the tunic of ascidians, has two peroxide moieties per molecule. Since ascidians are a widely served food item in Japan, human exposure to this compound potentially exists in the seafood preparation industries. No toxicological data have so far been published on this compound, and so we determined the intraperitoneal 6-day LD₅₀ in mice and conducted histopathological examinations. The 6-day LD₅₀, was found to be 199 mg/kg with 95% confidence limits of 126–314 mg/kg. Histopathological examination revealed necrosis induced in a variety of cells that had been directly exposed to the compound. These cells included hepatocytes, parenchymal pancreatic cells and fat cells. It is concluded that direct contact with this compound is likely to elicit cellular necrosis of various organs. The specific toxicological effects are probably dependent on the route of exposure.