Thrombopoietin in postoperative thrombocytopenia following living donor hepatectomy.

Thrombocytopenia is a frequent finding following living donor hepatectomy. It appears more pronounced in right graft donors than in left graft donors. This study analyzed postoperative thrombocytopenia in 20 living liver donors and examined the change of endogenous thrombopoietin (TPO) in its recovery. Platelet count, TPO level, fibrinogen degradation product (FDP), and D-Dimer were measured before surgery and on postoperative days (PODs) 1, 2, 3, 5, 7, and 14. Concurrently, liver and spleen volumes were calculated by computed tomography. Platelet count on POD 3 was significantly lower in right graft donors than in left graft donors (13.0 +/- 3.7 x 10(4)/microL vs. 16.8 +/- 4.0 x 10(4)/microL, P = 0.039) but recovered by POD 7 in all donors. Postoperative elevations of FDP and D-Dimer were significantly higher in right graft donors than in left graft donors. TPO level rose immediately after surgery, peaked on POD 5 in left graft donors and on POD 7 in right graft donors, and fell nearly to preoperative levels by POD 14. Postoperative TPO level per liver volume was significantly higher in right graft donors than in left graft donors. In conclusion, thrombocytopenia following living donor hepatectomy resolved within the first week regardless of graft type and was mainly associated with increasing consumption of circulating platelets, possibly due to intrahepatic and splenic congestion. With a reduced number of circulating platelets, TPO level rapidly increases. Also, with reduced consumption of platelets related to recovery from surgery, thrombocytopenia should resolve. As a consequence, TPO level would be expected to fall.     

Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.     

Body Image Changes in Adolescents II Comparison among Patients with Eating Disorders and Controls with Thin, Normal and Obese Body Shapes

Abstract: The Self-Rating Body Image (SRBI) test was used to determine whether the patients with eating disorders such as anorexia nervosa or bulimia showed their body image disturbance or not. The SRBI was completed by 120 subjects who consisted of 30 low weight (LW) controls, 30 normal weight (NW) controls, 30 high weight (HW) controls, 18 anorexic patients (AN) and 12 bulimic patients (BN). The AN group had a significantly greater dissatisfaction with the scales of the body shape, visceral organ and face image of the SRBI than the weight-matched LW group. The BN group had a significantly greater dissatisfaction with the visceral organ image than the weight-matched NW group. However, no significant difference in the body shape and face images between the BN and NW groups was found. Our results suggest that the anorexic patients may disturb more parts of the body image than the bulimic patients though both the anorexic and bulimic patients showed the disturbance of body image.     

When is total thyroidectomy indicated as a treatment of “follicular carcinoma”?

Clinicopathologic studies were performed to establish rational criteria for total thyroidectomy as a treatment of follicular carcinoma. During the 4-year period from 1981 to 1984, total thyroidectomy was carried out on 23 patients in whom unequivocal vascular invasion and/or obvious extracapsular extension were disclosed on pathological study of the primary thyroid lesion. Although occult metastatic lesions were detected postoperatively in 5 patients, no distant metastases have been found in 12. Distant metastasis was clinically manifest on admission in the other 6 patients. The degree of vascular invasion at the primary lesion was not correlated with the occurrence of distant metastasis. However, 10 of the 15 patients with tumors characterized by a thick fibrous capsule had distant metastases, while all but 1 of 8 patients with a thin capsule showed no metastasis. Apparent capsular invasion seemed to increase the relative risk of distant metastasis. On the other hand, solid clusters of tumor cells containing a variable number of small follicles, which characterize Langhans' wuchernde Struma, were found in 6 patients, and 5 of them showed distant metastases. Thus, total thyroidectomy should be considered when (a) distant metastases are clinically apparent, (b) the primary lesion has a thick fibrous capsule with or without obvious capsular invasion, or (c) solid clusters of tumor cells are demonstrated microscopically.

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Resumen Se realizaron estudios clinicopatológicos con el propósito de establecer criterios racionales para la tiroidectomía total en el tratamiento del carcinoma folicular. En el curso de un perfodo de 4 anos entre 1981 y 1984, se realizó tiroidectomía total en 23 pacientes en quienes se halló inequívoca invasión vascular y/o obvia extension extracapsular en el examen histopatológico de la lesión tiroidea primaria. Aunque postoperatoriamente se detectaron lesiones metastáticas ocultas en 5 pacientes, no se encontraron metástasis distantes en 12. Metástasis distantes eran clínicamente manifiestas en el momenta de la admisión en los otros 6 pacientes. El grado de invasión vascular en la lesión primaria no apareció correlacionado con la ocurrencia de metástasis distantes. Sin embargo, 10 de los 15 pacientes con tumores caracterizados por una cápsula gruesa y fibrosa tenían metástasis distantes, mientras solo 1 de 8 pacientes con tumores de cápsula fina mostró metástasis. La invasión capsular aparente parece incrementar el riesgo relativo de metástasis distantes. Por otra parte, agrupaciones sólidas de células tumorales con presencia de números variables de folículos pequeños, que caracterizan al wuchernde Struma de Langhans, fueron encontrados en 6 pacientes, 5 de los cuales mostraron metastasis distantes. Por lo tanto, se debe considerar la tiroidectomía total cuando: (a) haya metástasis distantes clínicamente aparentes, (b) la lesión primaria tenga una gruesa cápsula fibrosa con o sin invasión capsular obvia, y (c) se demuestren microscópicamente agrupaciones sólidas de células tumorales.

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Résumé Une étude clinicopathologique a été menée pour déterminer les critères de thyroïdectomie totale comme traitement dans le cancer folliculaire de la thyroïde. Pendant 4 ans, de 1981 à 1984, 23 patients ont subi une thyroïdectomie totale pour envahissement vasculaire non équivoque et/ou extension extracapsulaire évidente découverte sur la pièce d'exérèse initiale. Cinq patients avaient des métastases occultes découvertes dans la période postopératoire, 6 avaient des métastases cliniquement évidentes, alors que 12 ne présentaient aucun signe de métastase à distance. Le degré d'envahissement vasculaire de la lésion primitive n'était pas corrélé avec la survenue de métastases à distance. Cependant, 10 des 15 patients à tumeurs caractérisées par un épaississement de la capsule fibreuse avaient des métastases à distance, alors que 7 des 8 patients avec une capsule mince n'avaient pas de métastases. L'envahissement capsulaire était associé à un plus grand risque de métastases à distance. Des amas solides de cellules tumorales contenant de petits follicules, le wuckernde struma de Langhans, étaient retrouvés dans 6 cas, dont 5 avaient des métastases à distance. Ainsi, la thyroïdectomie totale est préconisée lorsque (a) des métastases à distance sont cliniquement évidentes, (b) la lésion primitive possède une capsule fibreuse épaisse avec ou sans envahissement évident, et (c) on met en évidence des cellules tumorales en amas microscopiquement.

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Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.     

The free radical scavenger edaravone suppresses experimental dextran sulfate sodium-induced colitis in rats

Recent studies suggest that the enhanced release of reactive oxygen species (ROS) plays an important role in the pathogenesis of clinical inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. In the present study, we investigated the effects of the free radical scavenger edaravone, which is used clinically as an anti-stroke agent, in the development of experimental dextran sulfate sodium (DSS)-induced colitis in rats. The rats were fed 4% (w/w of diet) DSS in standard powder chow for 8 days. The edaravone and vehicle saline were injected subcutaneously twice a day. After the experimental period, the wet colonic weight, macroscopic mucosal damaged area, histological damage score, mucosal myeloperoxidase (MPO) activity, mucosal tissue lipid peroxidate and serum interleukin-6 (IL-6) levels were measured. In the DSS-induced colitis model, edaravone treatment (1-20 mg/kg day) significantly reduced the wet colonic weight, macroscopic damaged area, and the histological damage score. Edaravone treatment also reduced mucosal MPO activity, mucosal tissue lipid peroxidate level and serum IL-6 level. In particular, edaravone at a dose of 20 mg/kg day significantly reduced mucosal MPO activity and serum IL-6 level. These results strongly support the involvement of ROS in the pathogenesis of DSS-induced colitis. A clinical effect for edaravone against IBD patients is strongly expected.     

Increased expression levels of integrin alphavbeta5 on scleroderma fibroblasts

Integrin alphavbeta5 is a receptor for vitronectin, a plasma glycoprotein that is also distributed in extracellular matrix of various tissues. Matrix-bound vitronectin has the potential to stabilize the active form of plasminogen activator inhibitor-1, resulting in the inhibition of the plasmin-mediated pericellular proteolytic cascade. In this study, we compared the levels of alphavbeta5 and matrix-bound vitronectin between normal and scleroderma fibroblasts and investigated the association with fibrosis. We demonstrated that alphavbeta5 was up-regulated on scleroderma fibroblasts. The up-regulated alphavbeta5 contributed to the increase in vitronectin-binding ability in scleroderma fibroblasts, which led to the vitronectin-dependent activation of plasminogen activator inhibitor-1. In immunohistochemistry, the alphav and beta5 subunits were stained strongly on scleroderma fibroblasts and the amount of vitronectin was increased in the pericellular matrix of those cells. The transient overexpression of alphavbeta5 on normal fibroblasts enhanced the human alpha2(I) collagen promoter activity through Sp-1 and Smad3 as well as the vitronectin-dependent plasminogen activator inhibitor-1 activity. This effect on the promoter activity was also observed in the absence of vitronectin and completely disappeared in the presence of anti-alphavbeta5 antibody. These results indicate that the up-regulated alphavbeta5 may contribute to the phenotypical alteration of scleroderma fibroblasts, while at the same time suppressing the plasmin-mediated pericellular proteolytic cascade.     

Sequence analysis of two serological variants, HLA-A2K and HLA-A9HH, detected in Japanese

Two rare variants of HLA-A locus antigens, tentatively called HLA-A2K and HLA-A9HH, were serologically identified in the Japanese population. A2K and A9HH showed short reaction patterns of a series of anti-A2 and anti-A9 sera, respectively. The latter variant also reacted with some anti-A2 sera. Nucleotide sequences of full-length cDNAs for A2K and A9HH were determined. The results revealed that both antigens are encoded by previously undescribed alleles. The nucleotide sequence of the allele for A2K was identical to that of A^*0207 except for a single nucleotide difference in exon 3. The nucleotide sequence of the allele for A9HH was identical to that of A^*2402 except for two nucleotides in exon 2. These two nucleotides are shared by all the reported A2 alleles. These sequencing results the allele for A9HH were consistent with the serological cross-reactivity of A9HH with some anti-A2 sera.     

gp49B1 suppresses stem cell factor-induced mast cell activation-secretion and attendant inflammation in vivo

We report that gp49B1, a mast cell membrane receptor with two immunoreceptor tyrosine-based inhibitory motifs (ITIM), constitutively inhibits mast cell activation-secretion induced by stem cell factor (SCF), a tissue-derived cytokine that also regulates mast cell development. The intradermal injection of SCF into the ears of gp49B1 null (gp49B(-/-)) mice elicited approximately 4- and 2.5-fold more degranulating mast cells and tissue swelling caused by edema, respectively, than in gp49B(+/+) mice. SCF did not induce tissue swelling in mast cell-deficient mice, and the responsiveness of gp49B(-/-) mice to mast cell-associated amine and lipid mediators was unaltered. When gp49B(+/+) and gp49B(-/-) mice were pretreated with antagonists of the amines, SCF-induced tissue swelling was reduced by >90% and 60%, respectively, and it was reduced by >90% in both genotypes when a cysteinyl leukotriene receptor antagonist was also provided. Hence, the dominant contribution of secretory granule amines to SCF-induced tissue swelling is the result of gp49B1-mediated inhibition of the production of cysteinyl leukotrienes by mast cells. Our findings also provide the first example of an ITIM-bearing receptor that constitutively suppresses inflammation generated in vivo independently of the adaptive immune response by a receptor that signals through intrinsic tyrosine kinase activity rather than immunoreceptor tyrosine-based activation motifs.     

Central nervous control of micturition and urine storage.

The micturition reflex is one of the autonomic reflexes, but the release of urine is regulated by voluntary neural mechanisms that involve centers in the brain and spinal cord. The micturition reflex is a bladder-to-bladder contraction reflex for which the reflex center is located in the rostral pontine tegmentum (pontine micturition center: PMC). There are two afferent pathways from the bladder to the brain. One is the dorsal system and the other is the spinothalamic tract. Afferents to the PMC ascend in the spinotegmental tract, which run through the lateral funiculus of the spinal cord. The efferent pathway from the PMC also runs through the lateral funiculus of the spinal cord to inhibit the thoracolumbar sympathetic nucleus and the sacral pudendal nerve nucleus, while promoting the activity of the sacral parasymapathetic nucleus. Inhibition of the sympathetic nucleus and pudendal nerve nucleus induces relaxation of the bladder neck and the external urethral sphincter, respectively. There are two centers that inhibit micturition in the pons, which are the pontine urine storage center and the rostral pontine reticular formation. In the lumbosacral cord, excitatory glutamatergic and inhibitory glycinergic/GABAergic neurons influence both the afferent and efferent limbs of the micturition reflex. The activity of these neurons is affected by the pontine activity. There are various excitatory and inhibitory areas co-existing in the brain, but the brain has an overall inhibitory effect on micturition, and thus maintains continence. For micturition to occur, the cerebrum must abate its inhibitory influence on the PMC.