SUBCELLULAR TYROSINASE ACTIVITY IN FORTNER''S MALIGNANT MELANOMA

SUMMARY. —Biochemical and macromolecular characterizations of Fortner's melanotic melanoma of Syrian (golden) hamsters and of B-16 melanotic mouse melanoma were made using the Warburg manometric technique for estimation of the subcellular distribution of tyrosinase activity.
The results showed that the major amount of tyrosinase activity was located in the soluble fraction of Fortner's malignant melanoma. This differs from the B-16 melanoma in which the major activity was in the large granule fraction with virtual absence of activity in the soluble fraction.
Substantial increase in the tyrosinase activity of Fortner's melanoma fractions was observed after prolonged incubation. The biological significance of this delay in attaining V_max is discussed.     

Risk of Long‐Term Dual Antiplatelet Therapy Following Drug‐Eluting Stent Implantation in Octogenarians

Objectives

To evaluate the risk of long‐term dual antiplatelet therapy (DAT) following drug‐eluting stent (DES) implantation in octogenarians.

Background

DES implantation requires DAT; however, DAT‐associated risk in octogenarians remains unclear.

Methods

Two‐hundred and six consecutive octogenarians (130 men, 83.3 ± 3.4 years) underwent stent implantation (104 bare metal stents [BMSs] and 102 DESs) and 38.0 ± 13.2 months of follow‐up.

Results

Significantly more DES patients received DAT. The incidence of bleeding events was similar in the DES and BMS groups for 1 year (total: 10.8% vs 5.8%, P = 0.19; major: 4.9% vs 2.9%, P = 0.70). However, after 2 years, significantly more bleeding events occurred in the DES group than the BMS group (total: 2 years, 21.6% vs 9.6%, P = 0.02; 3 years, 29.4% vs 11.5%, P = 0.001; 4 years, 31.4% vs 15.4%, P = 0.007; major: 2 years, 12.7% vs 3.8%, P = 0.04; 3 years, 18.6% vs 5.8%, P = 0.005; 4 years, 19.6% vs 6.7%, P = 0.006). Overall, significantly more total bleeding events (31.4% vs 15.4%, P = 0.007) and major bleeding events (19.2% vs 6.7%, P = 0.006) were observed in the DES group than in the BMS group. The adjusted hazard ratios and 95% confidence intervals (CI) were as follows: total bleeding events, 2.203 (95% CI: 1.065–4.556; P = 0.033); major bleeding events, 4.324 (1.506–12.414; P = 0.007).

Conclusions

DAT was associated with an increased risk of bleeding events in octogenarians after 2 years. DAT discontinuation should be considered for octogenarians 1‐year post‐DES implantation. (J Interven Cardiol 2013;26:114–122)

     

Recent Perspective on Coronary Bifurcation Intervention: Statement of the “Bifurcation Club in KOKURA”

The treatment of coronary bifurcation lesion remains a challenging issue even in the drug‐eluting stent era. Frequent restenosis and stent thrombosis have been recently shown to be related not only to geometrical gap or stent structural deformation but also to rheological disturbance. Low wall shear stress at the lateral side of the bifurcation is likely to cause atherosclerotic changes due to easy access of the macrophages that induce chemical mediators. The turbulent flow over stent metal may facilitate accumulation of platelets, which results in thrombosis. The jailed strut and excess metal overlap may increase these risks. Since dramatic changes of the coronary flow pattern at the bifurcation are closely related to the genesis of atherosclerosis, future bifurcation intervention technique should be considered to restore the original physiological state as well as the anatomical structure. This article summarizes the global consensus of the members of the Asian Bifurcation Club and European Bifurcation Club at the KOKURA meeting. It also provides a perspective of basic sciences relating to bifurcation anatomy, physiology, and pathology, in the search for a best strategy for bifurcation intervention. (J Interven Cardiol 2010;23:295–304)     

Clinical Study of Cyclocytidine in Children With Acute Leukemia

One hundred children with various types of leukemia were given113 treatments with cyclocytidine. Eighty-four of these patientshad been treated previously. Cyclocytidine was daily given intravenouslyfor four to 11 consecutive days in amounts of 20mg/kg or 500mg/m².The treatment course . was repeated, when necessary. Complete remission was obtained in one case of monocytic leukemiaamong six treated by cyclocytidine alone. Combined therapy withsteroid hormone gave 14 complete and eight partial remissionsin 38 cases, the remission rate standing at 58%. There were30 complete and 16 partial remissions in 69 cases treated withcombination therapy with two or more agents, and the remissionrate was 67%. Transient pains in the region of the parotid gland were themost characteristic toxicity. GI tract symptoms were less commonand milder than those of cytosine arabinoside. Dizziness wasnoticed in three cases. Nine children with acute leukemia who were given cyclocytidineorally showed no remarkable response. Cyclocytidine, given parenterally, seems beneficial for varioustypes of leukemia in children.     

Adrenocorticotropin-independent macronodular adrenal hyperplasia treated by simultaneous bilateral laparoscopic adrenalectomy

A 61-year-old woman was admitted to our hospital with hypertension and diabetes mellitus, and was found to have Cushing's syndrome. Radiological and endocrinological findings suggested adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. Simultaneous bilateral laparoscopic adrenalectomy was performed, minimizing the number of trocar sites and operation time. Success was attributed to the careful selection of trocar sites to permit safe dissection.     

Prominent induction of cyclin B1 in G2/M renal cancer cells with butyrolactone 1

BACKGROUND: Butyrolactone 1 (BL) is a cyclin dependent kinase (CDK) inhibitor derived from Aspergillus terreus. None of the present drugs are effective for the treatment of renal cell carcinoma. The use of BL is expected to promote a new type therapy of renal cancer. METHODS: We investigated three human renal cancer cell lines: ACHN, OS-RC-2 and RCC10RGB, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and two-color flow cytometry. Simultaneous measurements of DNA content and cyclin expression allowed us to perform cell cycle specific analysis. Western blot analysis was performed using ACHN to represent cell lines. RESULTS: BL inhibited cell proliferation and caused cell accumulation at G2/M phase associated with the emergence of the third peak. Moreover, BL induced cyclin B1 over-expression in G2/M cells. These changes were quite definite, whereas cyclins D1, E and A showed no changes at all. Cyclin B1 accumulation was confirmed by western blot analysis. The chronological observation revealed that the emergence of the third peak preceded the regression of the increased cyclin B1 positive G2/M cells. These results suggested that BL accelerated cyclin B1 accumulation in G2/M cells, which then shifted to G1 phase without cell division. New G1 cells started DNA synthesis most likely as endoreduplication to form the third peak and the mechanism of cyclin B1 accumulation converted into down-regulation. CONCLUSION: BL induced significant cell kinetic interference in the tested human renal carcinoma cell lines. This might indicate the possibility of a new medical treatment modality for renal cancer.     

Inhibitory Effect of NZ-105, a 1,4-Dihydropyridine Derivative,on Cyclic Nucloeotide Phosphodiesterase Activity

Abstract— The effects of NZ-105, a 1,4-dihydropyridine calcium antagonist, on the intracellular cyclic nucleotide system were investigated in-vitro. In rabbit isolated aorta, both NZ-105 (1 and 10 μm ) and nicardipine significantly and in a concentration-dependent manner increased intracellular cyclic AMP and cyclic GMP content. NZ-105 inhibited bovine cardiac phosphodiesterase activity (K_i 30 μm ) by competitive antagonism. The concentration ranges for inhibition were consistent with the range of increases in cyclic nucleotides.     

Isolation and characterization of tyrosinase inhibitors and their differential action on melanogenic subcellular compartments in amelanotic and melanotic melanomas

Further purification of highly active tyrosinase inhibitors by DEAE-Sephadex column chromatography has revealed that the mode of action of the inhibitors from melanomas with different melanogenic status is organelle specific. The inhibitor from amelanotic melanoma has a relatively strong suppressive effect on the tyrosinases in GERL and coated vesicle containing fractions. On the other hand, the inhibitor from melanotic melanoma has no substantial effect on these tyrosinases, although melanosomal tyrosinase is inhibited by both. The present evidence suggests that the defect of melanization in amelanotic melanoma in vivo is related to the tyrosinase inhibition of the smooth membrane system including GERL and coated vesicle by the highly active inhibitor characteristic of amelanotic melanoma.     

Acute fulminant ulcerative colitis with toxic megacolon

An 11-year-old boy with acute fulminant ulcerative colitis (UC) is presented. He had systemic deterioration with frequent diarrhea and lethargy. Acute fulminant UC associated with toxic megacolon was diagnosed by rectal endoscopy and biopsied specimen. He was treated with intensive intravenous administration of prednisolone and total parenteral nutrition. He recovered completely without any surgical intervention.