Effect of an endogenous satiety substance, 2-buten-4-olide, on gastric acid secretion and experimental ulceration in rats

The involvement of a feeding-related endogenous sugar acid, 2-buten-4-olide (2-B4O) on central regulation of gastric acid secretion, and its antiulcer effects on several gastric and duodenal experimental ulcer models were investigated in rats. Spontaneous gastric acid secretion was not affected by 2-B4O at doses below 10 mg/kg. The peripheral secretagogue-stimulated gastric secretions were significantly increased by pretreatment with 2-B4O. Gastric acid secretion induced by 2-deoxy-D-glucose (2-DG) was significantly suppressed by pretreatment with 2-B4O at doses between 0.1 and 100 mg/kg. Gastric and duodenal ulcerations induced by cold stress plus indomethacin, restraint and water immersion stress, pylorus ligation or cysteamine were also inhibited by pretreatment with 2-B4O. The results suggest that antiulcer effects of 2-B4O are due to suppression of gastric acid secretion via reduction of activity of the vagus nerve and gastric-related hypothalamic neurons. Thus, 2-B4O may be useful for treatment of gastroduodenal ulcer.     

Sarcomatoid carcinoma of the urinary tract

Sarcomatoid carcinoma is a rare variant of malignant tumor arising from the urinary tract. This tumor had been termed carcinosarcoma because of its carcinomatous and sarcomatous components. There is still some confusion in the terminology between true carcinosarcoma and sarcomatoid carcinoma; however, the latter is now regarded as primarily a malignant epithelial tumor with pseudosarcomatous transformation.
Four cases of sarcomatoid carcinoma arising from the urinary tract are reported. The patients were a 77 year old female, and three males aged 62, 69 and 80 years. All but the eldest patient complained of gross hematurla. Surgical removal was performed in the younger three cases, and an autopsy was done in the remaining case. All the tumors were macroscopically polypoid. Histopathologic examination revealed fasciculated spindle-cell tumors with myxold stroma or malignant fibrous histiocytoma-like spindle cell tumors. The epithelial nature was proven in these sarcomatous cells by immunohistochemical andlor electron-microscopic examinations. Only a small amount of squamous cell carcinoma components was also evident in the latter three cases. Although the younger three patients were alive at 44, 23 and 39 months'follow-up, respectively, constant careful monitoring Is recommended.     

Natural antibodies against the immunoglobulin F(ab′)2 fragment cause elimination of antigens recognized by the F(ab′)2 from the circulation

A humanized monoclonal IgG1 antibody, designated hC4G1, recognizes the fibrinogen receptor glycoprotein (GP)IIb/IIIa on platelets and inhibits platelet aggregation. When the F(ab′)₂ fragment of hC4G1 (F(ab′)₂ hC4G1) was administered to cynomolgus monkeys, all the monkeys showed inhibition of platelet aggregation ex vivo. Unexpectedly, a significant decrease in platelet count was observed in 5 of 18 monkeys. Antibodies against F(ab′)₂ hC4G1 were detected in the plasma of these monkeys by ELISA. Antibody activity in the plasma of these monkeys was significantly correlated with the intensity of platelet decrease (r = 0.84). The natural monkey antibodies to F(ab′)₂ hC4G1 were directed against the C-terminal region of F(ab′)₂ fragment common to all human and humanized IgG antibodies. Natural homo-reactive antibodies were also detected in human plasma from 15 of 40 healthy volunteers. Specificity was closely similar to that of the monkey antibodies. Affinity-purified human homo-reactive antibodies enhanced phagocytosis of platelets treated with the F(ab′)₂ hC4G1. Monkey plasma with high homo-reactive antibody activity was confirmed to decrease platelet count when administered together with F(ab′)₂ hC4G1 to a monkey with low antibody activity. These results suggest that F(ab′)₂ of humanized and human antibodies causes elimination of the corresponding antigens from the circulation by homo-reactive antibodies.     

Copper and iron-induced oxidative damage in non-tumor bearing LEC rats

The copper and Iron status in the liver of non-tumor bearing Long-Evans Cinnamon (LEC) rats (average age 17 months) was investigated. A direct quantitation of loosely-bound copper and iron was also investigated by using a chelating agent, nitrilotriacetic acid (NTA-chelatable free copper and iron). Besides the total copper and iron contents, the level of NTA-chelatable free copper was also higher in LEC rats than In LEA rats (P<0.05). But for the free iron level there was no signiflcant difference between the two rat groups (P>0.05). The formation of thiobarbituric acid-reactive substances was higher In LEC rats than In LEA rats (P<0.01). The 4–hydroxy-2–nonenal (HNE)-modified proteins were also clearly demonstrated in LEC rat liver. The copper and iron which produced the most important effect In the process of oxidative damage in LEC rats could not be distinguished. Even though free copper, which could induce free radical injuries, was increased in LEC rats, neither tumor-induction nor preneo-plastic lesions in the experimental LEC rats were observed. Therefore it is speculated that the elevation of a free iron is another important factor. Copper and iron, both important translation metals In the body, may participate In the Induction of DNA damage and oncogenesls     

Self-splicing of the Tetrahymena group I ribozyme without conserved base-triples

BACKGROUND: Group I introns share a conserved core region consisting of two domains, P8-P3-P7 and P4-P6, joined by four base-triples. We showed previously that the T4 td intron can perform phosphoester transfer reactions at two splice sites in the absence of both P4-P6 and the conserved base-triples, whereas it is barely able to perform the intact splicing reaction due to the difficulty of conducting the sequential reactions. RESULTS: Based on previous findings, we constructed a bimolecular ribozyme lacking a large portion of P4-P6 and the base-triples from the Tetrahymena intron, on the assumption that the long-range interactions of the peripheral regions in the two RNAs can compensate for the deteriorated core. The bimolecular ribozyme performed the intact splicing reaction. CONCLUSION: The present analysis indicates that the base-triples are nonessential, but that L4 and the distal part of P4 in P4-P6 are important for conducting the splicing reaction. The reconstituted self-splicing ribozyme provides an amenable system for analysing the role(s) of elements in the core region in the self-splicing reaction mechanism.     

Acute effect of inhaled beta(2)-agonists with different type of intrinsic activity on airway resistance in healthy volunteers]

Inhaled beta(2)-agonists (long-acting as well as short acting) are used world-wide for the relief of asthma symptoms. However, there are few reports which have evaluated the additive effect of short-acting beta(2)-agonists to long-acting beta(2)-agonists on airway resistance measured by a plethysmography. This study was designed to evaluate the additive effect of inhaled short-acting beta(2)-agonists (protecarol) to long-acting beta(2)-agonists (salmeterol) on airway resistance in normal healthy volunteers (S+P group). In addition, to compare the effects of beta(2)-agonists which have different types of intrinsic activities, acute effect of inhaled procaterol adding to procaterol was also evaluated (P+P group). Seven healthy volunteers (all male and all non-smokers) were entered in this study. Pulmonary function was measured by a body plethysmography. Forced expiratory volume per 1 second (FEV1), the maximum flow rate at 25% (V(.) 25), the maximum flow rate at 50% of forced vital capacity (V(.) 50), and airway resistance were measured before and after inhalation of salmeterol (1 dry powder, 50 microg) or procaterol (2 puffs, 20 microg). Sixty minutes after inhalation of salmeterol, or 15 minutes after inhalation of procaterol, inhalation of procaterol (2 puffs, 20 microg) was added, and then pulmonary function was monitored. FEV1, V(.) 25, and V(.) 50 were significantly increased after inhalation of salmeterol as well as procaterol. In addition, airway resistance decreased significantly after inhalation of salmeterol as well as procaterol. In the S+P group, additional decrease of airway resistance after inhalation of procaterol was relatively small compared with the P+P group. In conclusion, although additional bronchodilatoric effects were observed in the S+P and P+P group, the effects seemed to be different based on the intrinsic activity of each beta(2)-agonist.     

Epstein-Barr virus-related Hodgkin's disease showing B cell lineage in an immunosuppressive patient seropositive for HTLV-I

A case of Hodgkln's disease (HD), lymphocyte depression (LD) type In an Immunosuppressive patient is described. The patient was a 48-year-old male and his parents were born In the Kyushu area, which is an endemic area for adult T cell lymphomaheukemla (ATL). He was seropositive for ATL virus (ATLV, also referred to as HTLV-I) and showed a marked Immunosuppressive condition. He developed LD-HD and Pneumocystis carinii pneumonia, and died due to respiratory failure. The Immunohistochemical and in situ hybridization analyses revealed that the Reed-Sternberglike cells In the lymph node biopsy sample were positive for Ber-H2 (CD30), Leu-M1 (CD15), L-26 (CD20), Bcl-2, p53 and EBER, the viral genome of Epstein-Barr virus (EBV).     

Essential role of rho kinase in the ca2+ Sensitization of Prostaglandin F2α-Induced Contraction of Rabbit Aortae

Although the prostate gland is a rich source of α1-adreno- (α1-AR) and m1-cholino receptors (m1-AChR), the membrane processes associated with their activation in glandular epithelial cells is poorly understood. We used the whole-cell patch-clamp technique to show that the agonists of the respective receptors, phenylephrine (PHE) and carbachol (CCh), activate cationic membrane currents in lymph node carcinoma of the prostate (LNCaP) human prostate cancer epithelial cells, which are not dependent on the filling status of intracellular IP₃-sensitive Ca²⁺ stores, but directly gated by diacylglycerol (DAG), as evidenced by the ability of its membrane permeable analogue, OAG, to mimic the effects of the agonists. The underlying cationic channels are characterized by the weak field-strength Eisenman IV permeability sequence for monovalent cations ( P _K(25) > P _Cs(4.6) > P _Li(1.4) > P _Na(1.0)), and the following permeability sequence for divalent cations: P _Ca(1.0) > P _Mg(0.74) > P _Ba(0.6) > P _Sr(0.36) > P _Mn(0.3). They are 4.3 times more permeable to Ca²⁺ than Na⁺ and more sensitive to the inhibitor 2-APB than SK&F 96365. RT-PCR analysis shows that DAG-gated members of the transient receptor potential (TRP) channel family, including TRPC1 and TRPC3, are present in LNCaP cells. We conclude that, in prostate cancer epithelial cells, α1-ARs and m1-AChRs are functionally coupled to Ca²⁺-permeable DAG-gated cationic channels, for which TRPC1 and TRPC3 are the most likely candidates.