Giant occipital hemangioendothelioma with thrombocytopenia, anemia and hypofibrinogenemia treated by total excision (author's transl)]

An infant with a large occipital hemangioendothelioma with thrombocytopenia, anemia, and hypofibrinogenemia--Kasabach-Merritt syndrome--was reported. The case, a male neonate is unique, for this is the first report with this syndrome in whom the large hemangioma was noted at birth on the midocciput simulating the occipital encephalomeningocele. With the development of thrombocytopenia of 84,000 per mm3, hypofibrinogenemia of 92 mg/dl, anemia (erythrocyte 193 X 10(4) per mm3, hemoglobin 5.9 g/dl, hematocrit 16 vol%), hepato-splenomegalia, enlargement and bluish discoloration of the tumor noted on the 21/2 months of life, total excision was intended prior to the expected occurence of the systemic purpura. The patient received fresh whole blood transfusion immediately prior to surgery, and the total excision was successfully performed. Excessive bleeding was not encountered. Abrupt rise in the platelet count, red blood cell count, hemoglobin and hematocrit to normal range was noted at the first postoperative day; he was discharged on the 17th day after surgery. Nineteen months' follow-up showed normal hematologic findings with good somatic and mental development. The specimen weighing 250 g. revealed benigh hemangioendothelioma. Silver impregnation demonstrated lobular aggregates of small vascular channels. Papillary projection of interstitial cells into the lumen, reaction of the endothelium of the vessels, newly formed thrombus, ishemic necrosis and hemorrhage, hyaline degeneration of interstitial tissue were noted. These findings suggested the disseminated intravascular coagulation within the tumor followed by fibrinolysis accounts for loss of blood corpuscles, platelet, fibrinogen and clotting factors, which leads ultimately to the consumption coagulopathy and diffuse bleeding.     

Electrophoretic and Kinetic Studies of Mutant Erythrocyte Pyruvate Kinases

Thin-layer polyacrylamide electrophoresisand kinetic studies were used to differentiate three different mutant erythrocytepyruvate kinase (PK) in congenital nonspherocytic hemolytic anemia. In the firstfamily, proband and father had PK whichmigrated faster than the normal andhigh Michaelis—Menten constants (Km),whereas mother had normal migrationand kinetics, but low PK activity. In thesecond family, proband and mother hadPK which migrated slower than the normal. Proband had markedly high Km andmother intermediately high Km. In thethird family, proband and mother hadfaster migrating PK than the normal.Proband had high Km and mother had intermediately high Km. The parents in thesecond and third families were consanguineous. Inherited molecular abnormalities of erythrocyte PK were provento exist by abnormal electrophoretic mobilities, as well as abnormal results ofkinetic studies.

Submitted on May 4, 1973 Revised on October 10, 1973 Accepted on October 22, 1973     

Detection of cell surface antigens on monolayer cells: I. The application of immune adherence on a micro scale

A small scale modified method of the immune adherence on monolayer cells grown in Falcon plastic `Microtest' plates is described. This method is especially useful in mouse systems as it simplifies the washing procedure which is an indispensable step for removal of the anticomplementary activity present in mouse serum. Histocompatibility antigens and the surface antigen induced by the Moloney virus could be detected with this method.     

A case of stomach cancer in which TS-1 neoadjuvant therapy was effective against multiple hepatic metastasis,allowing a radical cure A surgery

It is believed that multiple hepatic metastases from stomach cancer are highly refractory, and resistant to clinical treatment. In the present study, TS-1 neoadjuvant therapy administered orally in a single course brought about CR in the hepatic metastatic foci and PR in the primary foci, thus enabling grade A radical extirpation in a case of advanced stomach cancer. The patient continued to be treated on an ambulatory basis. His peri- and post-operative courses were satisfactory and the treatment was completed without the development of adverse effects.     

Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines

Curcumin, traditionally used as a seasoning spice in Indian cuisine, has been reported to decrease the proliferation potential of prostate cancer cells, by a mechanism that is not fully understood. In the current study, we have evaluated the effects of curcumin in cell growth, activation of signal transduction, and transforming activities of both androgen-dependent and independent cell lines. Prostate cancer cell lines, LNCaP and PC-3, were treated with curcumin and its effects were further analyzed on signal transduction and expression of androgen receptor (AR) and AR-related cofactors using transient transfection assay and Western blotting. Our results show that curcumin down-regulates transactivation and expression of AR, activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), and CREB (cAMP response element-binding protein)-binding protein (CBP). Curcumin also inhibited the transforming activities of both cell lines as evidenced by the reduced colony forming ability in soft agar. The results obtained here demonstrate that curcumin has a potential therapeutic effect on prostate cancer cells through down-regulation of AR and AR-related cofactors (AP-1, NF-kappaB and CBP).     

Prostate specific antigen complexed to alpha-1-antichymotrypsin in patients with intermediate prostate specific antigen levels

BACKGROUND: The authors attempted to evaluate prospectively the usefulness of serum prostate specific antigen (PSA) complexed to alpha-1-antichymotrypsin (PSA-ACT) in the early detection of prostate carcinoma and its ability to discriminate between prostate carcinoma and benign prostatic hyperplasia (BPH), especially among patients with intermediate PSA levels. METHODS: Between December 1999 and August 2000, systematic sextant biopsies were performed on 281 prospective patients with prostate carcinoma who had serum PSA levels between 4.1 ng/mL and 20.0 ng/mL. The serum samples were assayed by using kits that were designed specifically for measuring serum PSA, PSA-ACT, and free PSA levels. The clinical values of PSA, PSA-ACT, the free PSA to total PSA ratio (F/T ratio), the free PSA to PSA-ACT ratio, PSA density (PSAD), and PSA-ACT density (ACTD) were compared by using receiver operating characteristic (ROC) curve analysis. RESULTS: Biopsy yielded no evidence of malignancy in 198 patients, and prostate carcinoma was confirmed in 83 patients. ROC analysis demonstrated that the area under the curve (AUC) for PSA-ACT was greater than that for total PSA and was equivalent to that for the F/T ratio in both groups of patients (PSA ranges of 4.1-20.0 ng/mL and 4.1-10.0 ng/mL, respectively). The AUC for the ACTD was greater than the AUC for the PSAD and had the highest value of all parameters. CONCLUSIONS: The measurement of PSA-ACT represents an alternative to the use of total and free PSA. The ACTD value is the most useful for discriminating between BPH and prostate carcinoma.     

Scalable enantioselective processes for chiral pharmaceutical intermediates

The importance and practicality of asymmetric synthesis to obtain enantiomerically pure drug substances has been fully recognized by process chemists of the pharmaceutical industry. Catalytic enantioselective processes would be particularly advantageous, compared to processes requiring stoichiometric amounts of chiral initiators, and would also be of interest from an environmental perspective. Since the commercialization of the Monsanto process for the manufacturing of L-DOPA in the early 1970s, catalytic asymmetric reactions have often been utilized in the commercial production of active pharmaceutical ingredients. This review will focus on recent advances in the development of scalable enantioselective processes for chiral pharmaceutical intermediates.