Bleeding from foveolar hyperplasia developing on a gastrointestinal stromal tumor of the stomach

A 52‐year‐old Japanese woman who presented with gastrointestinal (GI) bleeding underwent a proximal gastrectomy for a gastrointestinal stromal tumor (GIST) with a foveolar hyperplasia at the apex of the tumor, 4.5 cm in size, located in the upper body of the stomach. Although GIST are often asymptomatic and are found only incidentally, clinical symptoms such as bleeding, abdominal pain, or obstruction, occasionally lead to a premorbid diagnosis. When submucosal tumors present GI bleeding, the source of the bleeding usually is an ulceration of the mucosa over the tumor. However, in the present study, it was thought that the bleeding originated from the region of foveolar hyperplasia.     

Clonorchiasis complicated with duodenal papillary cancer in a visitor from China]

It is well known that long-term infection with Clonorchis sinensis often causes bile duct cancer, usually. It occurs in the intrahepatic bile duct. We encountered a rare case of clonorchiasis complicated with duodenal papillary cancer. The patient was a woman from China. Although clonorchiasis is rarely found in Japan, the promotion of international exchange may increase the number of visitors from endemic areas. Thus we must pay sufficient attention to this disease. Also, we reported that the microplate ELISA technique was useful in the diagnosis of clonorchiasis with high accuracy in this case.     

Disposition Characteristics of Macromolecules in Tumor-Bearing Mice

As part of the strategy for the design of macromolecular carriers for drug targeting, the disposition characteristics of macromolecules were studied in mice bearing tumors that served as target tissues. Eight kinds of macromolecules including four polysaccharides and four proteins with different molecular weights and electric charges were used; tissue distribution and tumor localization after intravenous injection were studied. Pharmacokinetic analysis revealed that the tissue radioactivity uptake rate index calculated in terms of clearance was different among the tested compounds; especially, the urinary radioactivity excretion clearances and the total hepatic radioactivity uptake clearances varied widely. Compounds with low molecular weights (approximately 10 kD) or positive charges showed lower tumor radioactivity accumulation; radioactivity was rapidly eliminated from the plasma via rapid urinary excretion or extensive hepatic uptake, respectively. On the other hand, large and negatively charged compounds, carboxymethyl dextran, bovine serum albumin, and mouse immunoglobulin G, showed higher radioactivity accumulation in the tumor (calculated total amounts were 15.6, 10.8, and 20.8% of the dose, respectively) and prolonged retention in the circulation. These results demonstrated that the total systemic exposure rather than the uptake rate index was correlated with total tumor uptake. Molecular weight and electric charge of the macromolecules significantly affected their disposition characteristics and, consequently, determined radioactivity accumulation in the tumor. It was concluded that a drug–carrier complex designed for systemic tumor targeting should be polyanionic in nature and larger than 70,000 in molecular weight.     

Role of protein kinase C in the modulation of multidrug resistance: expression of the atypical gamma isoform of protein kinase C does not confer increased resistance to doxorubicin.

Cross-resistance to anticancer drugs, termed multidrug resistance (MDR), is functionally associated with the expression of a plasma membrane, energy-dependent, drug efflux pump termed P-glycoprotein (PGP), the product of the mdr1 gene. We have shown previously that MCF-7 breast carcinoma cells transfected with the human mdr1 gene (BC-19 cells) exhibit greater MDR when stably transfected with protein kinase C alpha (PKC alpha). We now demonstrate that transfection of BC-19 cells with the gamma isoform of PKC (BC-19/PKC gamma cells), which is not normally present in BC-19 cells, does not confer increased resistance to doxorubicin, despite a 19-fold increase in PKC activity. All of the increased PKC activity is accounted for by PKC gamma and it is rapidly down-regulated by phorbol dibutyrate, within 15 min of treatment. Endogenous PKC alpha and PKC epsilon activities are not affected by phorbol dibutyrate. The cytotoxicity of doxorubicin was similar in BC-19/neo or BC-19/PKC gamma cells after either 2-hr or continuous drug exposure, and co-treatment with phorbol dibutyrate increased resistance to doxorubicin 4-fold in both cell lines. Phosphorylation of PGP was similar in both cell lines and drug accumulation was not affected by overexpression of PKC gamma. These results demonstrate that transfection of PGP-expressing cells with an atypical isoform of PKC does not confer increased MDR, and they suggest that the regulation of PGP is phenotype specific with respect to the isoform of PKC.     

Effects of intrahippocampal injections of N-methyl-D-aspartate receptor antagonists and scopolamine on working and reference memory assessed in rats by a three-panel runway task.

In order to elucidate the roles of hippocampal N-methyl-D-aspartate-type excitatory amino acid receptors in working and reference memory in rats, the effects of intrahippocampal injections of selective and competitive N-methyl-D-aspartate receptor antagonists such as CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid), 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid and 2-amino-5-phosphonovaleric acid on this behavior were examined with a three-panel runway task. The results were compared with the effect of the muscarinic receptor antagonist scopolamine. In the working memory task, CGS 19755 and 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid at 10 and 32 ng/side, injected bilaterally into the dorsal hippocampus before testing, produced a significant increase in the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points). This also occurred after the rats were given systemic injection of these drugs at 3.2 and 10 mg/kg. In the reference memory task, neither CGS 19755 nor 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid affected the number of errors, whether given at doses up to 32 ng/side intrahippocampally or up to 10 mg/kg systemically. Working memory errors also increased significantly after intrahippocampal injections of d-2-amino-5-phosphonovaleric acid at 100 and 320 ng/side, but were not affected by I-2-amino-5-phosphonovaleric acid at doses up to 1 microgram/side. On the other hand, intrahippocampal scopolamine at 1.0 and 3.2 micrograms/side increased significantly working memory errors, without affecting reference memory errors.(ABSTRACT TRUNCATED AT 250 WORDS)     

A surgical case of combined valvular disease complicated by absent right superior vena cava and persistent left superior vena cava.

A 74-year-old man with combined valvular disease with a recent cerebral infarction was admitted. While undergoing thorough examination for valvular disease, absent right superior vena cava (RSVC) and persistent left superior vena cava (PLSVC) were recognized. Chest X-ray film suggested a right arch protrusion, and CT and venogram confirmed the diagnosis. During surgery, replacement of the mitral and aortic valves and annuloplasty of the tricuspid valve were performed. A blood draining cannula was inserted in retrograde fashion from the coronary sinus into the PLSVC, without any difficulties in the tricuspid valve repair. Due to bradycardic atrial fibrillation, we believed that it would be difficult to insert an endocardial electrode postoperatively, hence myocardial electrode was placed in the right ventricular wall. Absent RSVC combined with PLSVC is very rare, and a patient who underwent combined valve surgery with this rare anatomical abnormality is herein presented.     

Nucleolus-associated J chains in myeloma cells: clinical significance

Bone marrow aspirates from 20 patients with multiple myeloma (MM), 4 with smoldering multiple myeloma (S-MM), 1 with idiopathic Bence Jones proteinuria (I-BJP), and 6 with primary macroglobulinemia (PMG) were examined for nucleolus-associated J chain. The incidence of nucleolar J chain-positive (J+) cells among nucleolated cells producing M-component was measured. This incidence (94.0-100%) in terminal MM was significantly higher than that (0-58.0%) in non-terminal MM. Judging from a low incidence in the remission phase, chemotherapy might cause a selective elimination of less differentiated myeloma cells with J+ nucleoli and might have some effect on J chain synthesis. The incidence of nucleolar J+ cells was very low in S-MM. The IgM cells in PMG, where J chain is present in a disulfide-linked form, had no or few J+ nucleoli. No correlation between the incidence of nucleolar J+ cells among nucleolated plasma cells and the percentage of nucleolated cells or that of J+ cells was found. Large J+ nucleoli seemed to be another morphological feature indicating anaplastic myeloma cells. A high incidence of nucleolar J+ cells may be one of the indicators for progressive disease.     

Case of dermatomyositis complicated with massive pleural effusion that preceded the myopathy]

A 36-year-old man was admitted to a hospital with complaints of fever, polyarthralgia and dyspnea. Erythema was observed on his face, extensor surface of the fingers and extremities, and a chest X-ray revealed massive bilateral pleural effusion. He had no sign of myopathy at this point. Pleural fluid was proved to be exudative and contained extremely high levels of hyaluronic acid. He was also complicated with interstitial pneumonitis and was given a pulse therapy with methyl prednisolone followed by daily administration of 55 mg prednisolone (PSL). Twenty days after the commencement of the therapy, pleural effusion decreased but muscle weakness gradually appeared, accompanied by elevation of myogenic enzymes. Myogenic changes on electromyogram, and irregularity of the muscle fibers with slight inflammatory cell infiltrates in a biopsy specimen were demonstrated. He was transferred to our hospital, and a diagnosis of dermatomyositis was made. Later, pleural effusion waxed and waned depending on the dosage of PSL, but no other causative disorder was demonstrated by extensive examinations. This case indicates that the pleuritis could be one of the vasculitic manifestations of dermatomyositis.     

Binding of lysozyme to lipopolysaccharide suppresses tumor necrosis factor production in vivo.

Endotoxin (lipopolysaccharide [LPS]) released during gram-negative bacterial infection induces varieties of cytokines which directly and/or indirectly cause shock, disseminated intravascular coagulation, and death. We previously showed that lysozyme (LZM) was an LPS-binding protein and inhibited various immunomodulating activities of LPS. In this study, we examined the effect of LZM on the LPS-triggered septic shock model induced by carrageenan treatment and assessed by tumor necrosis factor production. The data presented in this report strongly suggest that LZM-LPS complex formation completely abrogates tumor necrosis factor production and the mortality caused by LPS and that LZM may be useful for the treatment of endotoxin shock.