Granulomatous inflammation and monstrous giant cells in response to intraperitoneal hormone implants in channel catfish (Ictalurus punctatus)

Plastic implants (2.7 mm maximum dimension) of an ethyl vinyl acetate copolymer (EVAc) matrix, containing inulin, bovine serum albumin (BSA) and luteinizing hormone releasing hormone (LHRH), were covered with impervious EVAc and then surgically placed into the peritoneal cavity of 1-year-old channel catfish, Ictalurus punctatus. In fish kept in cold water (13 degrees C), 10 per cent of the implants per month were encapsulated by granulation tissue. In fish kept in warm water (27 degrees C), 20 per cent of the implants per month were encapsulated, with a total of 86 per cent encapsulated at 5 months. In addition to fibroblasts and capillaries, the granulation tissue included macrophages, neutrophils, lymphocytes, plasma cells, multinucleated giant cells and a matrix of collagen fibres. The density of the fibrous capsule increased with time. In a separate investigation, it was found that the thickness of the capsule was directly proportional to the degree of exposure of the EVAc matrix to the fish (exposure influenced by the rate of dissolution of the capsule content). Monstrous giant cells with up to 600 nuclei per 5 microns thick section were seen in capsules around implants. On intraperitoneally implanted cover glasses, whole giant cells contained up to 6000 nuclei and were interconnected by cytoplasmic bridges. Signs of neoplasia, implant expulsion or massive adhesions were not seen.     

Lactate dehydrogenase isolated from human liver mitochondria: its purification and partial biochemical characterization

We have demonstrated that lactate dehydrogenase is not solely a cytosolic enzyme by the isolation and purification of the enzyme from the mitochondria of human liver. Treatment of the mitochondria with digitonin reveals the LD activity to be associated with the inner membrane-inner matrix and the outer membrane. The mitochondrial LD consists of two fractions separated by ion exchange and affinity chromatography. The first mitochondrial fraction, LD-Mt1, with isoelectric points of 9.8, 9.6, and 4.8, has subunit components of 14500 and 34000 daltons. The second mitochondrial fraction, LD-Mt2, is similar to cytosolic LD-5 with respect to both isoelectric points and subunit molecular weight. The first mitochondrial fraction, LD-Mt1, has physical characteristics previously associated with the isoenzyme LD-6.     

Receiver Operating Characteristic (ROC) to Determine Cut-Off Points of Biomarkers in Lung Cancer Patients

The role of biomarkers in disease prognosis continues to be an important investigation in many cancer studies. In order for these biomarkers to have practical application in clinical decision making regarding patient treatment and follow-up, it is common to dichotomize patients into those with low vs. high expression levels. In this study, receiver operating characteristic (ROC) curves, area under the curve (AUC) of the ROC, sensitivity, specificity, as well as likelihood ratios were calculated to determine levels of growth factor biomarkers that best differentiate lung cancer cases versus control subjects. Selected cut-off points for p185^erbB-2 and EGFR membrane appear to have good discriminating power to differentiate control tissues versus uninvolved tissues from patients with lung cancer (AUC = 89% and 90%, respectively); while AUC increased to at least 90% for selected cut-off points for p185^erbB-2 membrane, EGFR membrane, and FASE when comparing between control versus carcinoma tissues from lung cancer cases. Using data from control subjects compared to patients with lung cancer, we presented a simple and intuitive approach to determine dichotomized levels of biomarkers and validated the value of these biomarkers as surrogate endpoints for cancer outcome.     

Effects of mutation and growth rates on patterns of microsatellite instability.

The detection of somatic microsatellite (MS) alterations in tumors is often interpreted as a sign of underlying genomic instability. However, it is unclear why the proportions of altered MS loci vary between different mutator phenotype tumors. We present a simple mathematical analysis that can account for some of these differences, recognizing that the mutations accumulated in a tumor reflect both its mutation rate and number of cell divisions. Only a small proportion of mutated MS loci are expected in tumors with normal or low mutation rates. In contrast, tumors with high mutation rates may or may not acquire mutations depending on the numbers of divisions that proceed the onset of the mutator phenotype. The majority of MS loci should accumulate mutations if high mutation rates are acquired early in tumor progression. Somatic MS mutations provide clues to both the mode and tempo of tumori-genesis.     

Guidelines to avoid personnel contamination by infective agents in research laboratories that use human tissues

Summary The personnel in laboratories that utilize tissue and fluids from humans and other primates are at risk for infection with agents, including the viruses causing hepatitis, AIDS, and other infective agents such as mycobacteria tuberculosis. To minimize the chance of infection of laboratory personnel, carefully organized policies and procedures to minimize exposure to infective agents must be established in research laboratories. We outline some of the approaches of hospital clinical laboratories which have proved most effective in minimizing transmission of infections from samples to laboratory personnel. Also, we discuss simple considerations important in the use and in the selection of safety equipment. These guidelines and references to other safety information are provided to aid research laboratories in establishing safety procedures that will minimize chances of personnel contamination with infective agents from research samples.     

Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in the BXD2 recombinant inbred strain of mice

The BXD2 strain of mice is one of approximately 80 BXD recombinant inbred (RI) mouse strains derived from an intercross between C57BL/6J (B6) and DBA/2J (D2) strains. We have discovered that adult BXD2 mice spontaneously develop generalized autoimmune disease, including glomerulonephritis (GN), increased serum titres of rheumatoid factor (RF) and anti-DNA antibody, and a spontaneous erosive arthritis characterized by mononuclear cell infiltration, synovial hyperplasia, and bone and cartilage erosion. The features of lupus and arthritis developed by the BXD2 mice segregate in F2 mice generated by crossing BXD2 mice with the parental B6 and D2 strains. Genetic linkage analysis of the serum levels of anti-DNA and RF by using the BXD RI strains shows that the serum titers of anti-DNA and RF were influenced by a genetic locus on mouse chromosome (Chr) 2 near the marker D2Mit412 (78 cm, 163 Mb) and on Chr 4 near D4Mit146 (53.6 cm, 109 Mb), respectively. Both loci are close to the B-cell hyperactivity, lupus or GN susceptibility loci that have been identified previously. The results of our study suggest that the BXD2 strain of mice is a novel model for complex autoimmune disease that will be useful in identifying the mechanisms critical for the immunopathogenesis and genetic segregation of lupus and erosive arthritis.