Use of a Paracorporeal Pneumatic Ventricular Assist Device for Postoperative Cardiogenic Shock in Two Children with Complex Cardiac Lesions

Pneumatic ventricular assist device (VAD) was utilized for cardiogenic shock after intracardiac operation in two children with complex cardiac anomalies based with single ventricle. In the first case (a 10-year-old), after a modified Fontan operation, VAD was placed between the functional left atrium and ascending aorta, serving as a "artificial single ventricle" with neither pumping chamber nor artificial support in the right side of the heart. The systemic circulation was maintained by keeping relatively high central venous pressure. In another child (a 3-year-old) who underwent repair of incompetent atrioventricular valve leaving intracardiac lesions, VAD was placed between the common atrium and ascending aorta, serving as a pump for both pulmonary and systemic circulation with regulation of pulmonary blood flow through an aortopulmonary Gore-Tex shunt. The circulatory assist with VAD was utilized for 5 and 6 days, respectively. Although weaning from the device was not feasible in both patients because of the pulmonary dysfunction, these experience showed the possible use of VAD for cardiogenic shock after surgery in patients with complex cardiac anomalies.     

The effect of a mixture of tegafur with uracil (UFT) on hepatocarcinogenesis in rats induced by 3'-methyl-4-dimethylaminoazobenzene. I. The influence on production of alpha-fetoprotein

We studied the effect of UFT (a mixture of Tegafur and uracil at a ratio of 1:4) on hepatocarcinogenesis and alpha-fetoprotein (AFP) production induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) in rats. By feeding rats with 3'-MeDAB diet, serum AFP started to appear from week 2-3 and increased until week 5-7, then declined until week 10-11. This phenomenon of a transient appearance of serum AFP is called "primary reaction". After week 11 hepatoma started to develop accompanied with an enormous elevation of serum AFP level until animals die, generally before week 25. Male Donryu strain rats fed a diet containing 0.06% 3'-MeDAB for 10 weeks, and then fed the normal diet. UFT was given by a stomach tube once a day for five days a week. Blood was collected from the tail vein every other week and serum AFP was measured by Rocket electrophoresis technique. When the administration of UFT (10 mg or 20 mg/kg/day) was started simultaneously with feeding 3'-MeDAB diet, the primary reaction was somewhat suppressed, and after week 11 development of hepatoma and elevation of AFP were markedly inhibited. The administration of UFT of a high dose (40 mg/kg/day) caused the death of animals in 7 weeks probably because of its toxicity. When the administration of UFT (10 mg or 20 mg/kg/day) was started after finish of feeding 3'-MeDAB diet for 10 weeks, the drug was not effective. These results show that if the administration of UFT was commenced at the same time with feeding 3'-MeDAB diet, the hepatocarcinogenesis and AFP production are strongly inhibited.     

Neurolysis of celiac plexus and splanchnic nerve under ultrasonographic guidance

Key words  intractable pain - celiac plexus neurolysis - ultrasonography     

Transient induction of single GST-P positive hepatocytes by DEN

The single cells positive for placental glutathione S-transferase(GST-P), detectable in livers of rats soon after treatment withhepatocarcinogens, are possible ‘initiated cells’,the hypothesis tested in the present series of experiments.No low dose threshold was observed in male Sprague-Dawley ratsat different single doses of diethylnitrosamine (DEM) althougha plateau was reached between 160 and 200 mg/kg body weight.At the latter single dose 12 400 positive cells/cm³ were observedimmunohistochemically in rat livers after one week, the numbersthen decreasing to week 8 and thereafter rising again. In thenumbers then decreasing to week 8 and thereafter rising again.In the early stages single cells predominated but with timea gradual increase in mini-foci and larger lesions became evident.Application of selection pressure (feeding of diet containing0.02% 2-AAF plus partial hepatectomy) to rats 2–24 weeksafter single DEN-treatment resulted in the formation of largefoci positive for GST-P, especially in the early stages, thegrowth response being less pronounced with time. The numberof foci, on the other hand. was correlated with the number offoci, on the other hand, was correlated with the number ofsingle cells/mini-foci detected inhepatectomy tissue of thesame individuals. These results suggest that the early GST-Ppositive populations could be the precursor for preneoplasticfoci and nodules.     

Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis

Ligation of the chemokine receptor CCR2 on monocytes and macrophages with its ligand CCL2 results in activation of the cascade consisting of phosphatidylinositol-3-OH kinase (PI(3)K), the small G protein Rac and lamellipodium protrusion. We show here that a unique clathrin heavy-chain repeat homology protein, FROUNT, directly bound activated CCR2 and formed clusters at the cell front during chemotaxis. Overexpression of FROUNT amplified the chemokine-elicited PI(3)K-Rac-lamellipodium protrusion cascade and subsequent chemotaxis. Blocking FROUNT function by using a truncated mutant or antisense strategy substantially diminished signaling via CCR2. In a mouse peritonitis model, suppression of endogenous FROUNT markedly prevented macrophage infiltration. Thus, FROUNT links activated CCR2 to the PI(3)K-Rac-lamellipodium protrusion cascade and could be a therapeutic target in chronic inflammatory immune diseases associated with macrophage infiltration.     

Molecular-based diagnosis of thyroid carcinoma: germ-cell carcinogenesis and aspiration biopsy nucleic acid diagnosis(ABND)

Recent data have shown the existence of specific changes in mRNAs in thyroid carcinomas. It has not been clarified, however, why these changes clearly distinguish benign tissues from carcinomas, while genomic alternation such as mutations in the RAS or P53 genes do not. Further, the widely believed hypothesis, multi-step carcinogenesis, does not explain some clinical and experimental evidence of thyroid carcinomas. Considering these facts, we propose a new idea for thyroid carcinogenesis called "germ-cell carcinogenesis", in which cancer cells are derived from the remnant of fetal thyroid germ cells(thyroblasts) instead of normal thyroid follicular cells. Utilizing such mRNAs, we have established a new method for preoperative molecular-based diagnosis of thyroid carcinomas, Aspiration Biopsy Nucleic Acid Diagnosis(ABND). ABND allows us to perform preoperative nucleic acid analyses of the tumors by extracting RNAs or DNAs from tumor cells obtained by fine needle aspiration biopsies(FNABs). Pathological diagnosis of thyroid follicular carcinoma is quite difficult, and the establishment of preoperative molecular-based diagnosis of follicular carcinoma has been long expected. We found that quantification of the trefoil factor 3(TFF3)/galectin-3 mRNA ratio in thyroid tumor cells is a useful tool for distinction between follicular adenomas and carcinomas. Because ABND can be performed without any severe invasion to the patients, in the near future, when more reliable systems of quantitative RNA analysis have been developed, ABND will probably become one of the standard tests for preoperative diagnosis of thyroid carcinoma.     

Recent advances in understanding the pathogenesis of polyglutamine diseases: involvement of molecular chaperones and ubiquitin-proteasome pathway

Polyglutamine diseases consist of a group of familial neurodegenerative disorders caused by expression of proteins containing expanded polyglutamine stretch. Over the past several years, tremendous progress has been made in identifying the molecular mechanisms by which the expanded polyglutamine tract leads to neuronal dysfunction and neurodegeneration. A common feature of most polyglutamine disorders is the occurrence of ubiquitin-positive neuronal intranuclear inclusions. The appearance of ubiquitinated aggregates implies an underline incapability of the cellular chaperones and proteasome machinery that normally functions to prevent the accumulation of misfolded proteins. Here we review the recent studies that have revealed a critical role for molecular chaperones and ubiquitin-proteasome pathway in the pathogenesis of polyglutamine diseases.     

Chymase participates in chronic dermatitis by inducing eosinophil infiltration

An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear caused a transient skin swelling, and the repetition of the challenge enlarged the contact dermatitis. The repeated challenge with DNFB also induced eosinophil infiltration on the application site. Administration of a chymase inhibitor significantly inhibited the ear swelling as well as eosinophil accumulation. An intradermal injection of human chymase to the mouse ear also elicited transient skin swelling and eosinophil infiltration, both of which were augmented in proportion to the number of injections. Human serum albumin and heat-inactivated chymase failed to induce such skin reactions, suggesting the participation of proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil migration in vitro in a concentration-dependent manner. Taken together, these observations suggest that mast cell chymase may contribute to development of the DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is therefore possible that chymase plays a role in pathogenesis of chronic dermatitis such as atopic dermatitis.     

Case of minocycline-induced pneumonitis with bilateral pleural effusion]

A 51-year-old man was admitted to our hospital with fever, dry cough and dyspnea. He had taken minocycline for 11 days because of urinary tract infection. Chest X-ray on admission showed diffuse reticular shadows in bilateral lung fields with bilateral pleural effusion. Cessation of minocycline led to spontaneous improvement of symptoms and radiographic findings. The lymphocyte stimulation test for minocycline with peripheral blood and pleural effusion were negative. After provocation test with minocycline, he developed fever and dry cough and bilateral ground glass opacity appeared on his chest X-ray. He was diagnosed as minocycline-induced pneumonitis and recovered rapidly following corticosteroid therapy.     

Biological functions of monospecific antibodies to envelope glycoproteins of Newcastle disease virus

Summary Monospecific antisera to HN and F glycoproteins of Newcastle disease virus were prepared, and their effects on the biological activities of the virus were investigated. Anti-HN serum inhibited hemagglutinating and neuraminidase activity, as well as hemolysis. Anti-F serum had no effect on hemagglutination or neuraminidase but inhibited hemolysis and virus-induced cell fusion.Anti-HN serum was highly neutralizing, while neutralization by anti-F serum was very inefficient in conventional plaque reduction tests, although both sera were estimated to contain comparable amounts of antibody reacting with the virus as indicated by complement fixation and immunodiffusion tests. The neutralizing activity of anti-F serum was greatly enhanced by the addition of anti-IgG serum or fresh guinea pig serum, whereas that of anti-HN serum was little enhanced.Anti-HN serum incorporated in the agar overlay suppressed the development of plaques to some degree, while anti-F serum had little effect. The combination of anti-HN and anti-F sera resulted in a marked decrease in the number and size of plaques, demonstrating the synergistic effect of the two species of antibody in the containment of the spread of viral infection.With 8 Figures