-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.     

Human parvovirus-induced transient anemia and leukopenia after delivery]

A 30-year-old female at 27 weeks' gestation, was hospitalized on September 24 1990 because of the premature rupture of the amniotic sac. She underwent Caesarean section on the same day with 700 ml blood loss, but no blood transfusion was required. For several days after the operation, her hemoglobin level remained 7.8 g/dl and did not increase significantly in spite of parenteral iron therapy. On the 9th postoperative day, chills and pyrexia developed with leukopenia. Bone-marrow aspiration revealed severe erythroblastopenia with giant proerythroblasts, suggesting recent HPV infection, which was confirmed by the presence of anti-HPV IgM and HPV antigen by ELISA. The hemoglobin level gradually decreased to 6.0 g/dl by the 21st day, then began to increase rapidly. The serum of acute-phase containing HPV antigens inhibited BFU-E and CFU-E but not CFU-GM. The serum of convalescent-phase inhibited neither erythroid colony growth nor myeloid colony growth. These results indicate that the inhibitory effect of HPV in colony assay is highly specific for erythropoiesis and that HPV play a role in transient cessation of erythropoiesis. The reason, however, for leukopenia in HPV infection remained unclear. This case shows that HPV infection may induce severe hematological disorders even in normal person under erythropoietic stress.     

Uptake of 99Tcm-MDP in lung metastasis from osteosarcoma: clinical and animal studies

Bone scintigraphy was performed in 17 patients with previously known lung metastases of osteosarcoma. 99Tcm-MDP uptake was observed in all primary bone lesions but lung metastatic lesions were positive in only six patients (35%). 99Tcm-MDP uptake by lung metastases was significantly correlated with bone and osteoid formation in the metastatic lesions and preoperative serum ALPase values. These clinical observations were confirmed by using nude mice transplanted with human lung metastatic osteosarcoma. 99Tcm-MDP scintigraphy appears to be useful for detecting lung metastases of osteosarcoma only in a selected group of patients.     

Characterization of inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current in rat phaeochromocytoma cells.

1. Inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current was characterized in rat phaeochromocytoma PC12 cells by use of whole-cell voltage-clamp techniques. 2. Haloperidol or chlorpromazine (1 and 10 microM) inhibited a K+ current activated by a test potential of +20 mV applied from a holding potential of -60 mV. The K+ current inhibition did not exhibit voltage-dependence when test potentials were changed between -10 and +40 mV or when holding potentials were changed between -120 and -60 mV. 3. Effects of compounds that are related to haloperidol and chlorpromazine in their pharmacological actions were examined. Fluspirilene (1 and 10 microM), an antipsychotic drug, inhibited the K+ current, but pimozide (1 and 10 microM), another antipsychotic drug did not significantly inhibit the K+ current. Sulpiride (1 or 10 microM), an antagonist of dopamine D2 receptors, did not affect the K+ current whereas (+)-SCH-23390 (10 microM), an antagonist of dopamine D1 receptors, reduced the K+ current. As for calmodulin antagonists, W-7 (100 microM), but not calmidazolium (1 microM), reduced the K+ current. 4. The inhibition by haloperidol or chlorpromazine of the K+ current was abolished when GTP in intracellular solution was replaced with GDP beta S. Similarly, the inhibition by pimozide, fluspirilene, (+)-SCH-23390 or W-7 was abolished or attenuated in the presence of intracellular GDP beta S. The inhibition by haloperidol or chlorpromazine was not prevented when cells were pretreated with pertussis toxin or when K-252a, an inhibitor of a variety of protein kinases, was included in the intracellular solution. 5. Haloperidol and chlorpromazine reduced a Ba2+ current permeating through Ca2+ channels. Inhibition by haloperidol or chlorpromazine of the Ba2+ current was not affected by GDP beta S included in the intracellular solution. 6. It is concluded that haloperidol and chlorpromazine inhibit voltage-gated K+ channels in PC12 cells by a mechanism involving GTP-binding proteins. The inhibition may not be related to their activity as antagonists of dopamine D2 receptors or calmodulin antagonists.     

Substance P induces inositol 1,4,5-trisphosphate and intracellular free calcium increase in cultured normal human epidermal keratinocytes

Abstract Substance P is a neuropeptide which is present in peripheral C nerve endings and released from them. Free nerve endings of C nerve are present in human epidermis. The effects of substance P on the transmembrane signaling system of pig epidermal sheets were previously reported. In these studies, a small amount of cells other than keratinocytes contaminated the epidermal sheets and the species difference from human was also noticed. Therefore we investigated the effects of substance P on cultured normal human epidermal keratinocytes. Alteration of intracellular free calcium (Ca²⁺) in single living keratinocytes was studied using an inverted fluorescence microscope and Ca²⁺ -sensitive dye, Fura 2-AM. Treatment of normal human epidermal kertinocytes with substance P resulted in an increase in inositol 1,4,5-trisphosphate and in intracellular Ca²⁺. Substance P inhibited DNA synthesis of the keratinocytes in a dose-dependent manner. These results are consistent with the view that substance P stimulates phosphatidylinositol-4,5-bisphosphate hydrolysis of human keratinocytes, resulting in inositol 1,4,5-trisphosphate-Ca²⁺ signal.     

Localization of proteins immunologically related to erythrocyte protein 4.1, spectrin and ankyrin in thyroid gland.

Analogues of erythrocyte protein 4.1, spectrin and ankyrin were examined in the thyroid gland of pig and rat by immunohistochemical techniques. Analysis with immunofluorescence microscopy revealed that the peripheral cytoplasm and apical-lateral plasma membrane of follicle epithelial cells of thyroid glands were stained with antibodies against erythrocyte protein 4.1, spectrin, or ankyrin. The results indicate that membrane skeletal protein lattice might exist in thyroid follicle epithelial cells.     

Left ventricular aneurysmectomy after myocardial infarction--comparative study between true aneurysms and functional aneurysms

Postinfarction left ventricular aneurysms are pathophysiologically divided into true, functional and false aneurysm. On 14 patients treated by aneurysmectomy, we studied the difference of pre- and post-operative cardiac function between true aneurysms (9 patients) and functional aneurysms (5 patients). The aneurysm area, which is expressed as the end-diastolic perimeter (akinetic or dyskinetic area/left ventricular silhouette), was 51.6 +/- 7.7% in the true aneurysms versus 35.7 +/- 6.0% in the functional aneurysms. Preoperatively, patients with a true aneurysm had a more severe clinical status than those with a functional aneurysm (Six of nine patients with a true aneurysm were in New York Heart Association functional class III or IV). Postoperatively, all patients except one with a true aneurysm and one with a functional aneurysm improved in clinical status. Nonaneurysmal EF, that is the function of the nonaneurysmal left ventricle, has a significant correlation to postoperative LVEF (r = 0.57, p less than 0.05). Nonaneurysmal EF was 54 +/- 4% in the true aneurysm group versus 51 +/- 16% in the functional aneurysm group. LVEF improved significantly (p less than 0.05) from 31 +/- 11% preoperatively to 55 +/- 10% postoperatively in the group of true aneurysm, but did not improved significantly from 43 +/- 12% to 50 +/- 9% in the functional aneurysm group. The postoperative akinetic area was 8.1 +/- 9.1% in the true aneurysm group versus 17.8 +/- 11.5% in the functional group. We conclude that larger and more adequate resection of aneurysms improves the cardiac function in the true aneurysm group more than in the functional aneurysm group.     

Dissecting aneurysm of the posterior cerebral artery treated with proximal ligation.

A rare case of a dissecting aneurysm of the P3 segment of the right posterior cerebral artery is presented that seems to have occurred in association with mild head injury. The patient was treated surgically because of repeated intramural hemorrhage and enlargement of the aneurysm. Proximal ligation produced thrombosis of the aneurysm without resulting in infarction in the region of the posterior cerebral artery. The mechanisms of the dissection, diagnosis, and treatment are briefly discussed.     

Gadolinium-based balloon angioplasty for pulmonary artery stenosis in an infant with a right isomerism.

We report here the first described case of utilizing gadolinium-based contrast material as the contrast agent during a catheter intervention treatment for pulmonary artery stenosis. The patient, a male infant with complex heart disease associated with a right isomerism, had a history of severe allergic reaction to iodine-containing contrast agents. A combination of digital subtraction angiography and a gadolinium contrast agent, however, provided us with good-quality images both before and after balloon angioplasty without any associated complications. This method should therefore be considered as an alternative angiographic procedure in children with a high risk of iodine-related allergic complications.