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.     

Role of proteasomes in the formation of neurofilamentous inclusions in spinal motor neurons of aluminum‐treated rabbits

We examined the role of the 20S proteasome in pathologic changes, including abnormal aggregation of phosphorylated neurofilaments, of spinal motor nerve cells from aluminum‐treated rabbits. Immunohistochemistry for the 20S proteasome revealed that many lumbar spinal motor neurons without intracytoplasmic neurofilamentous inclusions or with small inclusions were more intensely stained in aluminum‐treated rabbits than in controls, whereas the immunoreactivity was greatly decreased in some enlarged neurons containing large neurofilamentous inclusions. Proteasome activity in whole spinal cord extracts was significantly increased in aluminum‐treated rabbits compared with controls. Furthermore, Western blot analysis indicated that the 20S proteasome degraded non‐phosphorylated high molecular weight neurofilament (neurofilament‐H) protein in vitro. These results suggest that aluminum does not inhibit 20S proteasome activity, and the 20S proteasome degrades neurofilament‐H protein. We propose that abnormal aggregation of phosphorylated neurofilaments is induced directly by aluminum, and is not induced by the proteasome inhibition in the aluminum‐treated rabbits. Proteasome activation might be involved in intracellular proteolysis, especially in the earlier stages of motor neuron degeneration in aluminum‐treated rabbits.     

A case of quadricuspid aortic valve with aortic regurgitation

A 67-year-old man with grade 3 aortic valve regurgitation was found to have a quadricuspid aortic valve. The aortic valve consisted of 1 large, 2 intermediate and 1 small sized cusp. An accessory cusp located between the right and noncoronary cusps, and shaped like a hammock which sling by the fibrous strings originating from the both commissures to the aortic wall. Aortic valve replacement was successfully performed with a 23 mm St. Jude Medical prosthetic valve, and the patient is asymptomatic five months post-operatively. Histological examination of the resected cusps showed fibrous thickening and no rheumatic valvulitis or infective endocarditis.     

Evaluation of changes in portal collaterals by single photon emission CT: effects of endoscopic injection sclerotherapy

The changes in portal collaterals before and after Endoscopic Injection Sclerotherapy (EIS) for esophageal varices were studied by Single Photon Emission CT (SPECT). SPECT was performed for the intra-abdominal blood pool with 99mTc autologous red blood cells (RBC) in 17 patients with liver cirrhosis before and after EIS. Twenty mCi of 99mTc-RBC labeled by in vivo technique were administered intra-venously and tomographic imaging of the intra-abdominal vascular blood pool was performed as follows. For each subjects, 64 views were obtained over 360 degrees of elliptic rotation at 30 seconds per view. In 15 of 17 patients, blood pool images over coronary vein and/or short gastric vein area were clearly demonstrated on coronary images. In 9 of 15 patients, the pool of coronary vein or short gastric vein was disappeared or decreased after EIS. It is considered that intra-abdominal blood pool SPECT study is clinically useful for following up of hemodynamics of portal collaterals before and after EIS.