The intragastric tube feeding model is ideal for the study of the role of dietary factors and the effect of drugs on experimental alcoholic liver disease (ALD), since the model allows us to study the effect of a single variable in the diet on the pathology of liver where the blood alcohol level (BAL) is maintained over 150 mg%. By varying the dietary fatty acid composition we showed that the pathology was worsened by increasing linoleic acid or polyunsaturated fatty acids (PUFAs) in the diet where cytochrome P4502E1 (CYP2E1) was increased posttranslationally by high BAL. Concomitant with the increase in CYP2E1 there was evidence for an increase in lipid peroxidation (LP) by microsomes. Protein adducts of the products of LP were increased in the blood. Isoniazid (INH) enhanced this process and the pathology of ALD when INH was fed at therapeutic levels with ethanol. Preliminary studies show that diallyl sulfide, which inhibits and destroys liver CYP2E1 selectively, also modified the pathologic effects of ethanol. Thus we postulate that CYP2E1 induction plays a central role in the pathogenesis of ALD.

Allyl Compounds↗

PubMedDate not supplied

Synthesis and properties of an oligonucleotide modified with an acridine derivative at the artificial abasic site.

The synthesis of an oligodeoxynucleotide (ODN) modified with 2-methoxy-6-chloro-9-aminoacridine (Acr) at an abasic site is described. A stereochemically defined aminodiol, L-threoninol, was used to serve as artificial abasic nucleoside. The molecule was modified so as to be suitable for the standard phosphoramidite method and was incorporated into the interior of an ODN. In addition, N-hydroxysuccinimidyl N-[9-(6-chloro-2-methoxy)acridinyl]-6-aminocaproate has been synthesized for postsynthetic modification of the amino substrate of the L-threoninol moiety in the ODN. By using absorption spectroscopy, it is shown that oligo(dA) conjugated with acridine binds with complementary strand in a 1:1 ratio. The melting temperature showed that the nonmodified (abasic) duplex is destabilized as a result of lacking in base at the abasic site, but the covalently linked acridine ring compensates for the destabilization effect. The fluorescence quantum yield of the acridine ring was enhanced by connection to oligo(dA) and, further, by formation of a double-strand with the complementary ODN. The quantum yield is larger than that of intermolecular intercalation. The excitation spectra of Acr-ODN in the duplex is quite similar to the absorption spectra. The results indicate that the covalently linked acridine ring is selectively intercalated into the adjacent abasic site.

Acridines↗

PubMedDate not supplied

Optimization of rice alpha-amylase production using temperature-sensitive mutants of Saccharomyces cerevisiae for the PHO regulatory system.

A typical example of rational system synthesis for bioproduction by the cultivation of microorganisms harboring a recombinant plasmid was studied. First, two temperature-controllable expression systems for a foreign gene in Saccharomyces cerevisiae were constructed. The promoter of the PHO84 gene, which encodes an inorganic phosphate (Pi) transporter of S. cerevisiae and is controlled by Pi concentration through the PHO regulatory system, was used. And two temperature-sensitive mutants of S. cerevisiae for the PHO regulatory system were used as the host with rice alpha-amylase expression vector. One was temperature-sensitive pho81 mutant, SH3337, and the other was temperature-sensitive pho80 mutant, YKU107. When the strain SH3337 is cultivated at a lower temperature, the rice alpha-amylase gene connected downstream of the PHO84 promoter is expressed, but at a higher temperature, it is not. Conversely, with the strain YKU107, the transcription of the rice alpha-amylase gene is induced at a higher temperature and repressed at a lower one. The optimal cultivation temperature strategies for maximum production of rice alpha-amylase in batch cultures of these two recombinant strains were then determined by the Maximum Principle using the relationships of the specific growth and specific production rates to the cultivation temperature. The optimal strategies were easy to realize and were shown to be effective for maximum product. Finally, under these maximum alpha-amylase production strategies, the alpha-amylase activities and alpha-amylase yields in terms of glucose consumption for these recombinant strains were calculated on the basis of experimental data and compared for various operation times. The study demonstrates how a foreign gene expression system can be synthesized using a temperature-sensitive mutant with a given objective and under given constraints.

Biotechnology↗

PubMedDate not supplied

Improved patency of an elastomeric vascular graft by hybridization.

A newly devised hybrid graft with high antithrombogenicity for small caliber vascular grafts was developed. The design concept was based on the incorporation of a compliant open cell structured graft, autogenous endothelial cells (ECs), and artificial basement membrane. The latter, a gel complex of type I collagen and dermatan sulfate that showed enhanced adhesion and growth of ECs but reduced platelet adhesion, was coated onto a microporous polyurethane graft (internal diameter, 3 mm; length, 4.5 cm), with near-natural compliance. Ten seeded grafts were implanted bilaterally into the carotid arteries of dogs; anticoagulant or antiplatelet therapy was not administered. This hybrid graft showed a marked improvement in patency at 1 month compared with that of simply preclotted grafts (control specimens). This result was explained by the almost complete endothelialization when the graft was implanted, a high degree of adherent strength resistance to shear stress, and a high proliferative potential. Thus, this approach of combining biomechanical and cellular engineering designs may lead to an important functional small caliber graft.

Animals↗

PubMedDate not supplied

Progressive jaundice due to lymphangiosis carcinomatosa of the liver: CT appearance.

In a case of progressive jaundice, contrast-enhanced CT demonstrated unevenly distributed areas of periportal low attenuation throughout the liver that were demonstrated to be dilated lymphatics with multiple carcinomatous thrombi at postmortem study. This CT appearance may be characteristic of lymphangiosis of the liver.

Adenocarcinoma↗

PubMedDate not supplied

MR appearance of adenomatoid tumor of the uterus.

Reports on the radiological findings of adenomatoid tumor of the uterus are rare, and preoperative diagnosis is very difficult. To our knowledge, there have been no reports concerning the MR findings of adenomatoid tumor of the uterus. We report two cases of uterine adenomatoid tumor that showed the characteristic features of leiomyoma on MR images.

Adenomatoid Tumor↗

PubMedDate not supplied

Rat peripheral mononuclear cell thymidine kinase activity increases during liver regenerative processes after partial hepatectomy.

Deoxythymidine kinase (TK; EC 2.7.1.21) activity in the liver has been used as a marker of liver regeneration after partial hepatectomy. In this study we examined TK activity of various organs, plasma and peripheral blood mononuclear cells (PMNC) in 70% partially hepatectomized rats. TK activity of lymph nodes, small intestine, heart, lung, kidney and thymus did not increase significantly during the course of the study, except for spleen at 72 h. On the other hand, PMNC-TK and liver cystosolic TK activity increased in a parallel fashion at all times after partial hepatectomy; they began to increase 12 h after surgery and peaked 48 h post-surgery. Fractionation of PMNC into T cells and B cells revealed that both populations increased and peaked 48 h post-surgery. Plasma TK peaked 12-24 h after surgery, then declined at 36, 48 and 72 h after partial hepatectomy. This change paralleled plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PMNC-TK activity correlated significantly with liver cystosolic TK activity 24 h (r = 0.743; P < 0.05) and 48 h (r = 0.708; P < 0.05) after partial hepatectomy. However, it did not correlate with plasma levels of TK, AST and ALT. The results indicate that in the early stage of liver regeneration PMNC-TK may provide a marker of liver regenerative processes.

Alanine Transaminase↗