Genetic analysis of resistance to lethal infections of vesicular stomatitis virus in Syrian hamsters.

Vesicular stomatitis virus (VSV), Indiana serotype, causes a lethal disease in adult Syrian hamsters. Susceptibility to low doses of VSV (10 to 100 plaque-forming units) was shown to be genetically determined by examining six inbred strains. Three strains, LSH, MHA, and CB, were found to be extremely susceptible, with more than 70% of the animals dying within 72 h after intraperitoneal injection. Two strains, MIT and UT2, were intermediately susceptible, with approximately 60% of VSV-infected animals surviving. One strain, UT1, was found to be highly resistant; however, resistance was not acquired until the 4th or 5th week of age, and 100% of VSV-infected neonatal hamsters died. Analyses of F1 hybrid and segregant backcross populations derived from the LSH and UT1 strains suggested that at least three independent genetic loci contribute to phenotypic resistance. One locus resides on the X chromosome; the others reside on autosomes. No obvious linkage to the hamster major histocompatibility complex was detected. F1 hybrids of two highly susceptible strains, CB and MHA, were more resistant than either parental strain, suggesting that alleles of unlinked genes in the susceptible strains interact to produce a partially resistant phenotype. These alleles probably are the cause of the resistance phenotype found in the random-bred LVG strain which shares a common heritage with the CB and MHA strains.     

Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.      

阿魏酸钠对乙醇所致小鼠肝脏抗氧化功能改变的拮抗作用

研究了不同剂量乙醇对小鼠抗氧化和解毒功能的影响以及阿魏酸钠的拮抗作用。结果表明,大剂量乙醇(11.4g·kg^-1ig)引起肝脏GSH-Px活性升高的同时,肝脏GSH-Re,SOD和GST活性降低,GSH耗竭,而血清GST升高;阿魏酸钠(100mg·kg^-1ig,qd×10)预处理则明显拮抗大剂量乙醇所致的上述改变。表明阿魏酸钠对急性乙醇所致肝损害具有良好保护作用,其机理可能与提高GSH氧化还原酶功能、增加SOD活性和增强GSH结合反应有关。研究结果还提示,血清GST水平是反映乙醇性肝损害的灵敏指标。     

World Workshop on Oral Medicine VI: a systematic review of medication‐induced salivary gland dysfunction

The aim of this paper was to perform a systematic review of the pathogenesis of medication‐induced salivary gland dysfunction (MISGD). Review of the identified papers was based on the standards regarding the methodology for systematic reviews set forth by the World Workshop on Oral Medicine IV and the PRISMA statement. Eligible papers were assessed for both the degree and strength of relevance to the pathogenesis of MISGD as well as on the appropriateness of the study design and sample size. A total of 99 papers were retained for the final analysis. MISGD in human studies was generally reported as xerostomia (the sensation of oral dryness) without measurements of salivary secretion rate. Medications may act on the central nervous system (CNS) and/or at the neuroglandular junction on muscarinic, α‐and β‐adrenergic receptors and certain peptidergic receptors. The types of medications that were most commonly implicated for inducing salivary gland dysfunction were those acting on the nervous, cardiovascular, genitourinary, musculoskeletal, respiratory, and alimentary systems. Although many medications may affect the salivary flow rate and composition, most of the studies considered only xerostomia. Thus, further human studies are necessary to improve our understanding of the association between MISGD and the underlying pathophysiology.     

Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes

Two major types of lymphocytosis of large granular lymphocytes (LGLs) were observed. The proliferating LGLs in each type had distinct immunophenotypes, functional characteristics, and probably belonged to different cell lineages. The more common form (Type A) consisted of cells derived from the T cell lineage and had the T suppressor/cytotoxic phenotype (T11+, T3+, T8+). The expression of the Leu 7 and HLA-DR antigen was variable. These cells did not have natural killer (NK) function but showed a variable degree of antibody-dependent cell-mediated cytotoxic (ADCC) activity. Neutropenia was invariably present and rheumatoid arthritis and autoantibodies were frequent associations. These lymphocytes had many similarities to the major type of LGLs present in normal adult bone marrow. The other type of LGL lymphocytosis (Type B) consisted of cells lacking the antigens T3 and T8 but expressing M1 and NKH1. These cells possessed strong NK and ADCC activity but their cell lineage was not clear. Neutropenia and autoimmune phenomena were not detected. The cytochemical characteristics of the LGL granules from both types of patients were similar but differences in ultrastructure were observed. LGLs from Type B patients proliferated in the presence of Interleukin 2 (IL-2) and 12- O-tetradecanoyl-phorbol-13 acetate (TPA). Significant changes in their basic T11+, T3-, T8- phenotype were not observed. IL-2 and TPA, however, had profound influence on the NK function of the cells with enhancement in the case of IL-2 and marked suppression when stimulated by TPA.