Addition of mononucleotides to oligoribonucleotide acceptors with T4 RNA ligase.

RNA ligase induced by bacteriophage T4 catalyzed the addition of nucleoside 5',3'-diphosphates to oligoribonucleotide acceptors in the presence of ATP. The reactions proceeded in equimolar concentrations of donors and acceptors. Several oligonucleotides of defined sequence were synthesized by this method in yields of 28-68%. The enzyme required the phosphate ester at the 3' position of the donor molecule, nucleoside 5',2'-diphosphates being unable to serve as donors. Thymidine 5',3'-diphosphate was active as a donor for the enzyme. The ligation product, (Ap)2ApCp, was also obtained from the reaction of (Ap)2A and 5'-adenylylated cytidine 5',3'-diphosphate (A5'pp5'Cp) with RNA ligase in the absence of ATP. These results show that the minimal substrate for RNA ligase is a nucleoside 5',3'-diphosphate.     

Cloning and expression of murine interleukin-1 receptor antagonist in macrophages stimulated by colony-stimulating factor 1.

Colony-stimulating factor 1 (CSF-1) can act on mature macrophages to modulate their production of inflammatory cytokines. A cDNA encoding the interleukin-1 receptor antagonist (IL-1Ra) was cloned by subtractive hybridization from a CSF-1-stimulated murine macrophage cell line, sequenced, and expressed in mammalian and bacterial cells. Mouse IL-1Ra is a 22-Kd glycoprotein that is 76% identical to its human counterpart, shows considerably less similarity to IL-1 alpha and IL-1 beta, and competes with IL-1 alpha for binding to the type I IL-1 receptor normally expressed on T cells and fibroblasts. CSF-1 treatment of mouse bone marrow-derived macrophages led to a rapid and sustained increase in IL-1Ra mRNA during the G1 phase of the cell cycle as well as to increases in mRNAs encoding IL-1 alpha and IL-1 beta. Cycloheximide inhibited CSF-1-induced IL-1 alpha mRNA synthesis, but augmented IL-1 beta mRNA production and did not affect induction of IL-1Ra mRNA. No IL-1Ra mRNA was observed in CSF-1-stimulated mouse fibroblasts engineered to express CSF-1 receptors, demonstrating that its regulation depends on cell context and can be dissociated from the proliferative response. In agreement, bacterial lipopolysaccharide, a nonmitogenic activator, also induced IL-1Ra and IL-1 mRNAs in macrophages. Unlike IL-1 alpha and beta, IL-1Ra contains a signal peptide. The kinetics of its induction and its ability to gain access to the secretory compartment imply that IL-1Ra may be secreted more efficiently than IL-1, and suggest that macrophages both positively and negatively regulate the IL-1 response.     

Clinical improvements in higher brain function and rapid functional recovery in a case of cerebellar hemorrhage treated by neurocognitive rehabilitation

Cerebellar stroke rarely causes disorders of higher brain function such as cognitive deficits and emotional dysfunction; hence, the prognosis of these patients is uncertain. We report the case of a 34-year-old patient with cerebellar hemorrhage due to arteriovenous malformation causing higher brain dysfunction who was able to return to full-time employment after neurocognitive rehabilitation. Cerebellar stroke caused by nonatherosclerotic diseases or diaschisis may lead to cognitive deficits but these symptoms can be reversed by appropriate therapy. It is important to assess higher brain function in cerebellar stroke patients and to tailor neurocognitive rehabilitation programs appropriately to promote functional recovery.     

Pylorus-preserving pancreaticoduodenectomy with combined resection of the portal vein and gastrointestinal reconstruction by imanaga procedure for ductal cancer of the head of the pancreas

Twenty-six patients who underwent pyloruspreserving pancreaticoduodenectomy (PPPD) for ductal cancer of the head of the pancreas between 1983 and 1993 were reviewed. Gastrointestinal continuity was restored by the methods of Imanaga (n=21) and Traverso (n=5). Combined resection of the portal vein and/or superior mesenteric vein was performed in 13 patients. Surgical complications occurred in 5 patients, but there were no postoperative deaths. Delayed gastric emptying was observed in 42% of patients. The median survival time for all 26 patients was 13 months. Three patients survived for more than 3 years, and one of them is currently alive without recurrence at 10 years. Differences in survival rates were not apparent between patients who underwent PPPD with and without portal vein resection. Survival rate after PPPD was compared with that after pancreaticoduodenectomy (PD) performed between 1974 and 1992; the difference was not significant. Patients who underwent noncurative PPPD had a significantly better survival rate than those who underwent noncurative PD (P<0.05). PPPD has improved the quality of life of the resected patients, without reducing survival rate. At present, PPPD by the Imanaga procedure could be the best choice for management of cancer of the pancreatic head.     

Alcohol use in Hawaii

This article provides a review of the existing literature on alcohol use in Hawaii (i.e., epidemiology, reasons for use, associated problems, and intervention) and offers clinical implications of the findings and suggestions for further areas of research. In general, Caucasians, Hawaiians, younger Filipinos, males, adolescents, young adults, and those with lower educational attainment were found to be at higher risk. Overall, Hawaii's rates were either comparable or lower than those for the entire United States. Factors associated with different rates of alcohol use included accessibility, ability to resist offers, parent use and sanctions, peer influence and use, attitudes and beliefs (e.g., perceived normal drinking, dangerousness), religious affiliation, social occasions, and school intervention. Variable rates and trends in help-seeking behaviors, treatment admissions, and treatment utilization reflected the socio-cultural diversity in Hawaii. Perceived effectiveness of different treatments were generally consistent across ethnic groups, but did not necessarily represent actual efficacy. There is a clear need for additional prevention, screening, and intervention programs in Hawaii, including socio-culturally appropriate ones, as well as a need for further research.     

5-fluorouracil sensitivity and dihydropyrimidine dehydrogenase activity in advanced gastric cancer

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. Several studies have demonstrated the clinical importance of DPD in cancer patients, suggesting that the efficacy of 5-FU may be related to DPD activity in tumor tissue. In the present study, DPD activity and chemosensitivity to 5-FU were evaluated in advanced gastric cancer. Materials and METHODS: Thirty-four gastric cancers from 32 patients were studied and chemosensitivity to 5-FU was evaluated by histoculture drug response assay. RESULTS AND CONCLUSION: DPD activity and tumor inhibition of 5-FU among all cases showed no significant correlation, but among 14 histologically differentiated cases significant correlation was observed. DPD activity may be useful in determining the 5-FU sensitivity of differentiated gastric cancer.     

Free vascularized nerve grafting for immediate facial nerve reconstruction

OBJECTIVES/HYPOTHESIS: To obtain better functional results after reconstruction to treat facial palsy in the patients with preoperative and intraoperative factors that might inhibit functional recovery, the authors have used free vascularized nerve grafts to immediately reconstruct severed facial nerves. STUDY DESIGN: The indications for vascularized nerve grafts were 1) scarred recipient bed attributable to previous operations, 2) a history of previous irradiation at the wound, 3) facial skin defects over the nerve graft after tumor ablation, 4) patient age greater than 60 years, and 5) preoperative facial palsy. METHODS: Four types of free vascularized nerves were used. Functional recovery after reconstruction could be assessed with two facial nerve grading systems.Ten patients who underwent immediate reconstruction of severed facial nerve after ablative surgery of malignant tumors of the parotid gland were reviewed. RESULTS: Functional recovery after reconstruction could be assessed with the House-Brackmann grading system and a 40-point grading system in 6 of the 10 patients after a mean follow-up period of 29.8 months (range, 10-60 mo). Results with the House-Brackmann system were grade II in 1 patient, grade III in 4 patients, and grade IV in 1 patient; scores on the 40-point grading system were 20 in 1 patient, 22 in 3 patients, 24 in 1 patient, and 28 in 1 patient. CONCLUSION: The study results indicated that muscle movement recovers satisfactorily after free vascularized nerve grafting. Although a study comparing vascularized nerve grafts and conventional nerve grafts would be necessary to confirm the superiority of vascularized nerve grafts, free vascularized nerve grafts are effective for immediate reconstruction of the severed facial nerve in patients with preoperative and intraoperative factors that might inhibit functional recovery.