Morphology of the human and dog spleen with special reference to intrasplenic microcirculation

The terminal structure of splenic arterial capillaries, studied by scanning transmission electron microscopy, provided a three-dimensional view of the microarchitecture of human and dog spleens. There are reports that the terminal arterial capillaries end “openly” in the cord, however, our microphotographs indicate the possibility of a closed circulation in humans and dogs. In the human spleen, we found two types of arterial capillaries, one with a flat and continuous endothelium, and the other with discontinuous rod-shaped endothelial cells and a sheath-like structure. The microarchitecture and the termination of these arterial capillaries differ markedly among species. An abstract of this paper appeared in the Proceedings of the 19th Congress of the European Society for Surgical Research. (Zurich, 1984)     

Effect of genipin on the biliary excretion of cholephilic compounds in rats.

Aim: Genipin, a metabolite of geniposide, is reported to stimulate the insertion of multidrug resistance protein 2 (Mrp2) in the bile canalicular membrane, and to cause choleresis by increasing the biliary excretion of glutathione, which has been considered to be a substrate of Mrp2. In the present study, the effect of colchicine on the choleretic effect of genipin was investigated. The effect of genipin on the biliary excretion of the substrates of bile salt export pump and Mrp2 was also studied. Methods: After bile duct cannulation into rats, genipin was administered at the rate of 0.2 mumol/min/100 g, and the effect of colchicine pretreatment (0.2 mg/100 g) was examined. Metabolites of genipin in the bile were examined by a thin layer chromatography. Taurocholate (TC), sulfobromophthalein (BSP), and pravastatin were infused at the rate of 1.0, 0.2 and 0.3 mumol/min/100 g, respectively, and the effect of genipin co-administration was examined. Results: Genipin increased bile flow and the biliary glutathione excretion, and those increases were not inhibited by colchicine. The biliary excretion of genipin glucuronide was less than 10% of the genipin excreted into bile. The biliary excretion of TC, BSP, and pravastatin was unchanged by genipin co-administration. Conclusion: It was indicated that colchicine-sensitive vesicular transport has no role on the genipin-induced insertion of Mrp2 to the canalicular membrane. Choleresis of genipin is considered to be mainly due to the increased biliary glutathione excretion by genipin, not by the biliary excretion of glucuronide. TC had no effect on the biliary glutathione excretion.     

Atypical Wegener's granulomatosis with positive cytoplasmic antineutrophil cytoplasmic antibodies, ophthalmologic manifestations, and slowly progressive renal failure without respiratory tract involvement.

A 68-year-old woman had microscopic hematuria and proteinuria since the age of 50. She also had hearing impairment, arthralgia, retinal embolism, peripheral arterial occlusion of the right foot and chronic renal failure during the course. At the age of 68, she had progressive renal failure and nephrotic syndrome with high titers of serum cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). No evidence of respiratory tract involvement was found. Methylprednisolone pulse therapy and low dose cyclophosphamide therapy ameliorated the renal failure and reduced the serum c-ANCA level. She, however, died on July 19, 1998 due to pulmonary fungal and pneumocystis carinii infection.     

Inhibitory Effects of Curcumin and Tetrahydrocurcuminoids on the Tumor Promoter-induced Reactive Oxygen Species Generation in Leukocytes in vitro and in vivo

The inhibitory effects of curcumin and two tetrahydrocurcuminoids on tumor promoter-induced oxidative stress in vitro and in vivo were investigated. Curcumin, tetrahydrocurcumin (THC) and dihydroxytetrahydrocurcumin (DHTHC) exhibited significant inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced O₂-generation in differentiated HL-60 cells. The inhibitory activity of THC was weaker than that of curcumin. This tendency was the inverse of the results of previous studies on in vitro antioxidative activity against lipid peroxidation. The curcuminoids inhibited TPA-induced intracellular peroxide formation in differentiated HL-60 cells. THC exhibited much weaker inhibition of intracellular peroxide formation than curcumin, suggesting that this inhibition might be attributable to the inhibition of O₂-generation. The inhibitory effects of curcuminoids on TPA-induced H₂O₂ formation in female ICR mouse skin were further examined using the double-TPA-application model. Each TPA application induces two distinct biochemical events, 1) recruitment of inflammatory cells to the inflammatory regions and 2) activation of oxidant-producing cells. Double pretreatment of mice with curcuminoids before each TPA treatment significantly suppressed double TPA application-induced H₂O₂ formation in the mouse skin. Coadministrations of curcumin with either first or second TPA treatment significantly inhibited H₂O₂ formation. In addition, THC tends to show weaker inhibitory activities than curcumin in bioassays related to tumor promotion, i.e., inhibition of tumor promoter-induced inflammation in mouse skin and Epstein-Barr virus activation. These tendencies were parallel to those in the tumor-suppressive potential of curcumin and THC in mouse skin, as previously reported. Thus, we concluded that curcuminoids significantly suppress TPA-induced oxidative stress via both interference with infiltration of leukocytes into the inflammatory regions and inhibition of their activation.     

Clinical characteristics of seafood allergy and classification of 10 seafood allergens by cluster analysis]

The aim of this study was to investigate the clinical characteristics of children who showed sensitization to any type of seafood and to classify the 10 seafood allergens based on IgE reactivities by a cluster analysis. In children with bronchial asthma (BA) and/or atopic dermatitis (AD), we defined the 'seafood' group as 23 patients having any type of seafood specific IgE antibody (CAP system). We analyzed the clinical features, the serum total IgE and each allergen specific IgE level. In addition, ten seafood allergens were also classified by a cluster analysis. Three patients revealed immediate hypersensitivity to some seafood. The frequency of patients with AD and the total IgE in the seafood group were high and the patients in this group were tend to be sensitized to multiple allergens. Seafood allergens were classified into 4 groups, 1) salmon, sardine, horse mackerel and mackerel, 2) cod and tuna, 3) octopus and squid, and 4) crab and shrimp, by a cluster analysis. These findings corresponded to the biological classification and the classification by the reported common allergens among various types of seafood. Based on our findings, this classification is therefore considered to be useful when selecting allergens to screen for sensitization to seafood.     

Video-assisted transaortic left ventricular thrombectomy and coronary artery bypass grafting

A 59-year-old man with cardiac dysfunction was admitted to our hospital because of thrombus formation in the left ventricle 10 days following acute myocardial infarction. Echocardiography revealed evidence of two mobile thrombi, each measuring about 2 cm in diameter. Urgent coronary artery bypass grafting and video-assisted transaortic thrombectomy were performed without making a left ventricular incision to preserve his cardiac function. Endoscopy was useful for visualizing the anatomical structures in the left ventricular cavity.     

Synergistic effect of electric pulses and bleomycin on cultured rabbit subconjunctival fibroblasts

• Background: The combined effect of electric pulses (EP) and antiproliferative agents on the proliferation of rabbit Tenon’s capsule fibroblasts was investigated. • Methods: Rabbit Tenon’s capsule fibroblasts were cultured. Some of these cells were exposed to various intensities of EP alone (500–2500 V/cm). Other cells were then exposed for 30 min to an antiproliferative agent: bleomycin (BLM; 0.0005-50 μmol/l), mitomycin C (MMC; 0.0005-50 μmol/l), 5-fluorouracil (5-FU; 0.05-5000 μmol/l), or streptomycin (SM; 0.0005-50 μmol/l) with or without EP (2000 V/cm, 99 μs, eight pulses). Cell proliferation was assessed by cell counting on day 3 and by a ³H-thymidine uptake assay. DNA fragmentation was assessed by flow-cytometric analysis and agarose gel electrophoresis. • Results: A significant reduction in the cell number was observed only at 2500 V/cm (P<0.05). BLM, MMC and 5-FU treatment inhibited cell proliferation in a dose-dependent manner either with or without EP (ID₅₀: BLM alone, 0.029 μmol/l; BLM and EP, 0.00022 μmol/l; MMC alone, 41.6 μmol/l; MMC and EP, 27.5 μmol/l; 5-FU alone, 1045 μmol/l; 5-FU and EP, 690.2 μmol/l; P<0.05). EP treatment induced an inhibitory effect of BLM on cell proliferation which was 100 times more prominent than BLM alone (0.0005 μmol/l of BLM alone 103.4 ± 4.4%, 0.0005 μmol/l of BLM and EP 26.0 ± 4.4%; P = 0.021). BLM treatment with EP also augmented the apoptotic-like DNA fragmentation in both a flow-cytometric DNA histogram and agarose gel electrophoresis. • Conclusion: EP treatment enhanced the inhibitory effect of BLM on the cell proliferation of Tenon’s capsule fibroblasts of rabbits. The combination of electric pulses and antiproliferative drug treatments may therefore reduce the necessary dose of antiproliferative agents in filtering surgery.     

Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a calcium antagonist: beyond the renoprotective effects of ACE inhibitor monotherapy in a spontaneous hypertensive rat with renal ablation.

To assess the renal benefits of combined angiotensin-converting enzyme inhibition and calcium antagonism, we studied the antihypertensive and renoprotective effects of temocapril (TMP) alone or in combination with azelnidipine (AZN) in a spontaneously hypertensive rat (SHR) remnant kidney model of chronic renal failure. Male 5/6-nephrectomized SHR/Izumo rats were randomly assigned to receive vehicle (control group), TMP (TMP group; 10 mg x kg(-1) x day(-1)), AZN (AZN group; 3 mg x kg(-1) x day(-1)), or both (TMP+AZN group) orally for 12 weeks. Systolic blood pressure (SBP) and urinary excretion of albumin (UalbV) were measured every 2 weeks. At the end of the experiment, serum creatinine (Scr), heart weight (HW), and blood urea nitrogen (BUN) levels were measured and the remnant kidneys were examined to determine the index of glomerular sclerosis (IGS). SBP and UalbV in the control group increased progressively throughout the experimental period. TMP, AZN, and TMP+AZN blocked the development of hypertension. TMP+AZN did not enhance the antihypertensive effects of either TMP or AZN used singly. TMP, AZN, and TMP+AZN all significantly decreased the UalbV, Scr, BUN, and HW/body weight (BW) ratio. The level of UalbV and the HW/BW ratio in the TMP+AZN group were significantly lower than those in the TMP and AZN groups, and the level of Scr in the TMP+AZN group was significantly lower than that in the TMP group. TMP, AZN, and TMP+AZN all significantly protected against an increase in the IGS. The IGS in the TMP+AZN group was significantly lower than that in the TMP and AZN groups. These results indicate that both TMP and AZN have antihypertensive and renoprotective effects in this model. They also suggest that simultaneous administration of TMP and AZN provides greater renoprotective effects than TMP alone.