Lim and Spirin [25] proposed a preferable conformation of the nascent peptide during the ribosomal transpeptidation. Spirin and Lim [26] excluded the possibilities of the side-by-side model proposed by Johnson et al [13] and the three-tRNA binding model (A, P and E sites) of Rheinberger and Nierhaus [3]. However, a slight conformational change at the 3' end regions of both A and P site tRNA molecules can enable the three different tRNA binding models to converge. With a modification of the angles of the ribose rings of both anticodon and mRNA this model can also be related to the model of Sundaralingam et al [19]. In this model of E coli rRNA the 3' end sequence ACCA76 or GCCA76 of P site tRNA is base-paired to UGGU810 of 23S rRNA, while the ACC75 or GCC75 of A site tRNA are base-paired to GGU1621 23S rRNA. The conformation of the A76 of A site tRNA is necessarily different from that of P site tRNA, at least during the course of the transpeptidation. The A76 of A site tRNA overlaps the binding region of puromycin. The C1400 of 16S rRNA in this model is located at a distance of 4 A from the 5' end of the anticodon of P site tRNA [14] and 17 A from the 5' end of the anticodon of A site tRNA [15]. It is also shown that a considerable but reasonable modification in the conformation of the anticodon loops could lead to accommodation of three deacylated tRNA(Phe) molecules at a time on 70S ribosome in the presence of poly(U) as observed experimentally [6]. A sterochemical explanation for the negatively-linked allosteric interactions between the A and E sites is also shown in the present model.

Allosteric Regulation↗

PubMedDate not supplied

Primary structure of the alpha-subunit of Torpedo californica (Na+ + K+)ATPase deduced from cDNA sequence.

Sodium- and potassium-dependent ATPase [(Na+ + K+)ATPase], which is responsible for the active transport of Na+ and K+, is distributed universally among animal cell membranes and consists of two types of subunits, alpha and beta (refs 1-4). The larger alpha-subunit with a relative molecular mass (Mr) of 84,000-120,000 is thought to have the catalytic role. We have now cloned and sequenced DNA complementary to the Torpedo californica electroplax messenger RNA encoding the alpha-subunit of (Na+ + K+)ATPase and have deduced the complete amino-acid sequence of the polypeptide. Some structural features of the alpha-subunit molecule related to the function of this active-transport protein are discussed.

Amino Acid Sequence↗

PubMedDate not supplied

Effects of loxoprofen sodium, a newly synthesized non-steroidal anti-inflammatory drug, and indomethacin on gastric mucosal haemodynamics in the human.

Non-steroidal anti-inflammatory drugs (NSAID) are, and have been, frequently used for alleviation of pain in patients; however, they are known to cause gastric mucosal injury in experimental animals and in humans. A decrease in the gastric mucosal blood flow also plays an important role in the aetiology of acute gastric mucosal injury, as we previously reported. This study investigated the effect of a newly synthesized NSAID, loxoprofen sodium (sodium 2[p-2 oxocyclopentylmethyl) phenyl]propionate dihydrate, on gastric mucosal haemodynamics using a reflectance spectrophotometry system. Both single and cross-over methods were used in five volunteer subjects. Loxoprofen sodium 60 mg (one tablet) or indomethacin 25 mg (one tablet), was diluted in 10 mL water at 25 degrees C and sprayed on the gastric mucosa via a polyethylene tube inserted into the biopsy channel of an endoscope. After drug administration, reflectance spectra were taken every 5 min for 30 min. The indices of mucosal haemoglobin content (IHb) and oxygen saturation of haemoglobin (ISO2) were determined by the method previously reported by the authors. Indomethacin administration produced a significant decrease in both IHb and ISO2 values, indication ischaemia. Loxoprofen sodium, however, showed no significant differences in either of the parameters. Haemorrhagic erosions were evident after indomethacin administration, but none were found after loxoprofen sodium administration. The conclusion reached on the basis of this evidence is that one-time topical application of loxoprofen sodium is safer than indomethacin.

Administration, Oral↗

PubMedDate not supplied

Stabilization in microsomal membranes of the fifth transmembrane segment of the Na+,K(+)-ATPase alpha subunit with proline to leucine mutation.

We have reported that the fifth transmembrane segment of the Na+,K(+)-ATPase alpha subunit could not be inserted into microsomal membranes when it was synthesized from the truncated alpha 1 cDNA. In this study, three proline residues in the segment were changed into leucine residues by site-directed mutagenesis. Replacement of all three proline residues by leucine residues allowed the insertion of this segment and its translocation. This result confirms our previous finding and demonstrates that three proline residues in the fifth transmembrane segment prevent insertion of the segment into the membrane.

Amino Acid Sequence↗

PubMedDate not supplied

The non-surgical treatments of hepatocellular carcinomas in a patient with severe hemophilia A.

We recently treated a patient with multiple hepatocellular carcinomas (HCC) who had severe hemophilia A and thrombocytopenia secondary to cirrhosis. He was not a candidate for surgery because of his liver failure. Transcatheter arterial chemoembolization and percutaneous ethanol injection therapy were successfully performed without complications by maintaining factor VIII levels above 40%. We believe that the non-surgical treatment of HCC can be performed safely in patients with coagulation disorders, by the appropriate administration of coagulation factors, despite thrombocytopenia and/or elongation of the prothrombin time from cirrhosis.

Adult↗

PubMedDate not supplied

An autopsy case of multilocular cystic hepatocellular carcinoma without liver cirrhosis.

Although simple cysts, cystadenoma and cystadenocarcinoma of the liver have been well documented as hepatic cystic diseases, cystic hepatocellular carcinoma is a curious entity. Only 3 cases have been reported in the English literature. A 70-year-old man was admitted to Nagoya University Hospital for multiple liver tumors and a thrombus in the main trunk of the portal vein. A part of the tumors contained cystic components, and were diagnosed as hepatocellular carcinoma by needle biopsy. After giving informed consent, the patient was treated with several systemic chemotherapy using doxorubicin, fluorouracil, cyclophosphamide, cisplatin and oral anticancer agent UFT, a combination of uracil and tegafur, for almost 2 years. During this time, the tumors enlarged gradually, and also underwent cyst formation, the patients then died of biliary sepsis. Autopsy confirmed the diagnosis of multilocular cystic hepatocellular carcinoma without liver cirrhosis.

Aged↗

PubMedDate not supplied

A case of the development of two hepatocellular carcinomas and a cholangiocarcinoma with cirrhosis after elimination of serum hepatitis C virus RNA with interferon therapy.

A 64-year-old man who had exhibited abnormal transaminase levels for about 20 years was admitted to a hospital for the treatment of liver damage. Laboratory testing demonstrated that he was suffering from chronic hepatitis C, and a liver biopsy showed chronic active hepatitis with septal fibrosis. He was treated with interferon-alpha, and HCV-RNA became undetectable. Four years after the completion of interferon treatment, 3 lesions in the patient's liver were revealed by routine ultrasonography, and he was referred to Nagoya University Hospital for further examinations on November 1997. Radiographical examinations such as computed tomography and angiography demonstrated 2 hypervascular tumors (size: phi 35 mm and phi 20 mm) and 1 hypovascular tumor (phi 28 mm). Qualitative analysis for HCV-RNA by polymerase chain reaction method was negative. Partial hepatectomy was performed, and pathological examination of the tumors showed 2 moderately differentiated hepatocellular carcinomas and cholangiocarcinoma accompanied with liver cirrhosis. We propose that even patients with disappearance of HCV-RNA after interferon therapy, especially with liver cirrhosis or severe fibrosis, should be followed-up closely and examined at regular intervals because of the high risk of developing primary liver cancers.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Endoscopic appearances of hemorrhagic peptic ulcers and efficacy of H2-receptor antagonists.

BACKGROUND/AIMS: In this retrospective study, we compared the effects of histamine H2-receptor antagonists to those of antacids and anticholinergics in patients with hemorrhagic ulcers with various endoscopic appearances of bleeding. PATIENTS AND METHODS: Patients with hemorrhagic ulcers (n = 376) were examined by emergency endoscopy and were treated with 1) antacids and anticholinergic drugs or 2) H2-receptor antagonists. RESULTS: In ulcer patients with oozing or fresh red coagulation, H2-receptor antagonists ceased further hemorrhage more effectively (65.9% of the cases) than antacids and anticholinergic drugs (46.7%). In patients with projectile bleeding, both of the treatments failed to stop hemorrhage. There were no significant differences in favorable outcome in the patients only with old black coagulation between antacid and anticholinergic drugs-treated group and H2-receptor antagonists-treated group (94.4% and 93.8%, respectively). CONCLUSIONS: The results suggest that H2-receptor antagonists are more effective than antacids and anticholinergic drugs in patents with peptic ulcer with fresh coagulation or oozing, but not with projectile bleeding or old black coagulation. The results also indicate that endoscopic appearances of peptic ulcer bleeding are good predictors for the effects of medication.

Adolescent↗