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PubMed1993

Biologic and molecular characterization of non-Hodgkin's lymphoma.

The wide clinicopathologic heterogeneity of non-Hodgkin's lymphoma is reflected by the various molecular pathways underlying non-Hodgkin's lymphoma pathogenesis, including activation of dominantly acting oncogenes, deletion and inactivation of tumor-suppressor genes, viral infection, deregulation of cytokine networks, and chronic antigenic stimulation. Molecular lesions involving protooncogenes include activation of bcl-2 and bcl-1 in specific subsets of low-grade non-Hodgkin's lymphomas and c-myc in a proportion of intermediate- and high-grade non-Hodgkin's lymphomas. The deregulation of these genes promotes cell growth or protects the tumor population from programmed cell death, or both. Additional genetic abnormalities representing putative sites of novel oncogenes contributing to lymphomagenesis include chromosomal breaks at 3q27 in intermediate-grade non-Hodgkin's lymphoma and at 9p13 in small lymphocytic lymphoma. The role of inactivation of tumor-suppressor loci is best exemplified by the frequent inactivation of p53 in Burkitt's lymphoma and by the recurrent deletion of 6q25-q27 and 6q21-q23 in intermediate- and high-grade non-Hodgkin's lymphoma, respectively. Infection by Epstein-Barr virus occurs in a variable fraction of high-grade non-Hodgkin's lymphomas, whereas it is usually absent in other types of non-Hodgkin's lymphoma. Other mechanisms supporting non-Hodgkin's lymphoma growth and development include autocrine or paracrine cytokine loops, or both, and clonal expansion through antigen receptor stimulation. The heterogeneity of non-Hodgkin's lymphoma pathogenesis provides a framework for the development of novel classification methods of potential clinical relevance.

Cyclin D1↗
PubMed1992

Malignant rhabdoid tumour of the liver. A case report.

A case of primary malignant rhabdoid tumour of the liver occurring in a 5-month-old girl is reported. Histologically the neoplasm presented the 'typical' features as described in malignant rhabdoid tumour arising in the kidney. In addition, some areas of the tumour showed a 'pseudoglandular' growth pattern. Immunohistochemistry revealed the neoplastic cells to be intensively positive for vimentin and for cytokeratin 19. Variable immunoreactivity for cytokeratin polypeptides 7, 8 and 19 was also detected. On electronmicroscopy the neoplastic cells contained bundles of intermediate filaments, tonofilaments and intercellular junctions. These findings are suggestive of a primitive epithelial differentiation.

Biomarkers↗
PubMed1990

Reduced plasminogen activator inhibitor activity in high consumers of fruits, vegetables and root vegetables.

We studied a cross-sectional sample of 260 subjects aged 30-60 years, in order to assess the relation between food intake habits and factors of the fibrinolytic system. Plasma samples of tissue plasminogen activator (tPA) antigen, and plasminogen activator inhibitor (PAI-1) activity were obtained for the assay. The dietary pattern was determined using a food frequency questionnaire, according to which the subjects were grouped as high, low or medium consumers. The subjects who were high consumers of fruit, vegetables, and root vegetables showed the lowest levels of PAI-1, those who were low consumers had the highest levels, whereas the medium consumers showed intermediate values. The tPA levels did not differ between the three groups, and there were no significant differences in other variables that covaried with PAI-1 levels, such as age, anthropometric variables, or serum lipid levels, which could confound the PAI-1/food pattern relationship. The data, which show that a frequent intake of fruit, vegetables, and root vegetables--foodstuffs rich in vitamin C and fibre--is associated with lower PAI-1 levels, are consistent with increased activity of the fibrinolytic system and thus a reduced risk of thromboembolic and cardiovascular disease in subjects who exhibit this food intake pattern.

Adult↗
PubMed1995

Kinetoplast maxicircle DNA replication in Crithidia fasciculata and Trypanosoma brucei.

Kinetoplast DNA, the mitochondrial DNA of trypanosomatids, is composed of several thousand minicircles and a few dozen maxicircles, all of which are topologically interlocked in a giant network. We have studied the replication of maxicircle DNA, using electron microscopy to analyze replication intermediates from both Crithidia fasciculata and Trypanosoma brucei. Replication intermediates were stabilized against branch migration by introducing DNA interstrand cross-links in vivo with 4,5',8-trimethylpsoralen and UV radiation. Electron microscopy of individual maxicircles resulting from a topoisomerase II decatenation of kinetoplast DNA networks revealed intact maxicircle theta structures. Analysis of maxicircle DNA linearized by restriction enzyme cleavage revealed branched replication intermediates derived from theta structures. Measurements of the linearized branched molecules in both parasites indicate that replication initiates in the variable region (a noncoding segment characterized by repetitive sequences) and proceeds unidirectionally, clockwise on the standard map.

Animals↗
PubMed2002

Base composition of mononucleotide runs affects DNA polymerase slippage and removal of frameshift intermediates by mismatch repair in Saccharomyces cerevisiae.

The postreplicative mismatch repair (MMR) system is important for removing mutational intermediates that are generated during DNA replication, especially those that arise as a result of DNA polymerase slippage in simple repeats. Here, we use a forward mutation assay to systematically examine the accumulation of frameshift mutations within mononucleotide runs of variable composition in wild-type and MMR-defective yeast strains. These studies demonstrate that (i) DNA polymerase slippage occurs more often in 10-cytosine/10-guanine (10C/10G) runs than in 10-adenine/10-thymine (10A/10T) runs, (ii) the MMR system removes frameshift intermediates in 10A/10T runs more efficiently than in 10C/10G runs, (iii) the MMR system removes -1 frameshift intermediates more efficiently than +1 intermediates in all 10-nucleotide runs, and (iv) the repair specificities of the Msh2p-Msh3p and Msh2p-Msh6p mismatch recognition complexes with respect to 1-nucleotide insertion/deletion loops vary dramatically as a function of run composition. These observations are relevant to issues of genome stability, with both the rates and types of mutations that accumulate in mononucleotide runs being influenced by the primary sequence of the run as well as by the status of the MMR system.

Base Composition↗
PubMed1990

Do nurses or doctors have an increased risk of developing multiple sclerosis?

A cluster of multiple sclerosis (MS) patients has been reported in seven of 307 nurses in Key West, Florida. The MS death rates in British nurses and qualified medical practitioners were looked at and no increased mortality from multiple sclerosis was found. Neither was there an increase in mortality from motor neuron disease (amyotrophic lateral sclerosis), the control disease. Death rates from MS vary with social class, being highest in social class IIIN (skilled non-manual) and lowest in social class II (intermediate). These different rates may be due to MS causing health related occupational mobility. Allowance for the inter-class variability in MS death rates did not materially affect the conclusion that death from MS appears to be no more common than expected among nurses and doctors than in the general population. Possible explanations for the cluster of multiple sclerosis among nurses in Key West are discussed.

Adult↗
PubMed2002

Evaluation of the SNAP foal IgG test for the semiquantitative measurement of immunoglobulin G in foals.

The SNAP Foal IgG test (IDEXX) as evaluated for its accuracy and usefulness by measuring blood samples collected from 42 foals between 24 and 48 hours after birth. The results were compared with the single radial immunodiffusion (SRID) test as the reference method. The SNAP test was quick and easy to perform, and the results were similar to those obtained by SRID in 64 per cent of the samples. The best results were found with low (< 400 mg/dl) and high (> 800 mg/dl) concentrations of immunoglobulin G, with an accuracy of 80 per cent and 89 per cent, respectively. The intermediate concentrations were usually lower when measured by the SNAP test than by the SRID test, possibly owing to the variable volume of blood added to the test with the sample loop.

Animals↗
PubMed1975

The basis for differences in ethanol-induced myocardial depression in normal subjects.

The acute effects of ethanol (ETOH) on cardiac function in 32 normal subjects has been studied utilizing systolic time intervals. Seven (group I) 13 (group II), and 12 subjects (group III), reported an average daily consumption of less than 1 oz, 1-2 oz, and more than 2 oz of ETOH, respectively. Progressively higher control values from group I to group III in PEP, PEPI, ICT and PET/LVET were observed (PEP-I vs PEPI-III: P smaller than 0.05; PEP/LVET-I vs PEP/LVET-II and PEP/LVET-III: P smaller than 0.05). There was progressively less change in these variables following acute ETOH (P smaller than 0.02-0.05 in group I; P equals NS in group III, group II intermediate). This indicates some degree of chronic myocardial impairment in group II and especially in group III, which tends to be proportionate to the degree of chronic ETOH exposure. These data are not necessarily disparate with previous reports of little or even a salutary hemodynamic effect of ETOH in normal subjects. Thus, the relative stability of LVET post ETOH, coupled with the observed increase in heart rate, is consistent with previous reports of ETOH-induced rate-dependent increments in cardiac output with unchanging stroke volumes, in spite of the presence of acute myocardial depression. The observations reported herein demonstrate the probable incremental influence of ETOH consumption in a chain of events which may culminate in alcoholic cardiomyopathy.

Adult↗
PubMed1991

Multivariate analysis of prognostic factors in stage IV follicular low-grade lymphoma: a risk model.

We analyzed the records of 96 previously untreated patients with stage IV follicular low-grade lymphoma (FLGL) uniformly treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) chemotherapy from 1972 to 1982. The overall complete remission (CR) rate was 77%. At a median follow-up of 138 months, the 10-year cause-specific survival rate was 42% with a median survival of 100 months. Failure-free survival (FFS) was 15% at 10 years with a median FFS of 30 months. Multivariate analysis showed peripheral lymph node size (LN), degree of marrow involvement, and sex, in that order, to be important for FFS, while the number of extranodal sites (#ENS), LN, sex, and degree of marrow involvement were important for cause-specific survival. We devised a tumor burden (TB) model, incorporating #ENS, LN, and degree of marrow involvement. Three groups were identified with statistically significant differences in cause-specific survival and FFS. Those with low TB (one ENS exclusive of extensive marrow and nodal disease less than 5 cm) had a 10-year cause-specific survival of 73% compared with 24% for patients with high TB (greater than or equal to two ENS and nodal disease greater than or equal to 5 cm) (P less than .001) and 40% for those with intermediate TB (either greater than or equal to 2 ENS, or extensive marrow only, or nodal disease greater than 5 cm) (P = .050). Patients with low TB had a 10-year FFS rate of 32%, while the intermediate and high TB groups had 10% and 9% FFS, respectively (P = .003). Because sex was a very strong prognostic variable, we created a risk model for survival and FFS based on TB and sex. Females with low TB had the best prognosis (92% survival and 50% FFS at 10 years) and males with high TB had the worst outlook (median survival and FFS, 43 and 12 months, respectively). Other TB-sex combinations defined two groups with statistically significant differences in survival but comparable FFS. This model should aid in the design and analysis of future trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1980

Local contrast and maintained generalization.

Pigeons received variable-interval reinforcement for key pecking during presentations of horizontal and vertical line-orientation stimuli, while pecks during five intermediate orientations were extinguished. Lowest peck rates were observed during presentations of negative stimuli adjacent to the positive orientations while peck rate during 45 degrees (the intermediate negative orientation) was relatively high, i.e., there were negative contrast shoulders. When peck rates were manipulated in the positive orientations, peck rate in neithboring orientations changed in the opposite direction. Contrast shoulders faded after prolonged training. A second type of contrast, local contrast, was correlated with similarity of preceding stimulus and different average peck rates during different stages of the discrimination process. The data suggest that sequential local contrast accompanying the formation of a discrimination contributes to the form of generalization gradients. Blough's model of stimulus control predicts the changes in gradient form described here, but may not accurately depict the underlying process responsible for gradient form.

Animals↗
PubMed2000

Proliferation of immature myeloma cells by interleukin-6 is associated with CD45 expression in human multiple myeloma.

Multiple myeloma (MM) is a hematologic malignancy of human plasma cells, and myeloma cells can be classified into several subpopulations according to phenotypic differences, such as CD38 MPC-1- CD49e- immature, CD38 MPC-1+ CD49e- intermediate and CD38 MPC-1+ CD49e+ mature myeloma cells. The expression of the CD45 molecule on myeloma cells is quite variable, and the physiological consequence of CD45 on myeloma cells is still unknown. Recently, we have found that a few MPC-1- immature myeloma cells express CD45 antigens while most myeloma cells do not express the CD45. MPC-1- CD45+ CD49e- but not MPC-1- CD45- CD49e- immature cells contain proliferating cells in response to interleukin-6 (IL-6). IL-6 can also induce expression of CD45 on the MPC-1- CD45- subpopulation of immature myeloma cells. In addition, myeloma cell lines responding to IL-6 express CD45, whereas cell lines proliferating independent of IL-6 do not express CD45. In the U266 cell line, IL-6 leads to the induction of CD45 expression and cell proliferation, indicating that IL-6-induced effects are closely linked to CD45 expression. Thus, there is a heterogeneity in human myeloma cells, and among these subpopulations immature myeloma cells expressing the CD45 molecules appear to proliferate in response to IL-6. In this review we propose the involvement of CD45 in MM pathogenesis, and the possible implications of CD45 as both a phenotypic marker and a functional molecule is discussed.

Antigens, Neoplasm↗
PubMed2001

Use of the gram stain in microbiology.

The Gram stain differentiates bacteria into two fundamental varieties of cells. Bacteria that retain the initial crystal violet stain (purple) are said to be "gram-positive," whereas those that are decolorized and stain red with carbol fuchsin (or safranin) are said to be "gram-negative." This staining response is based on the chemical and structural makeup of the cell walls of both varieties of bacteria. Gram-positives have a thick, relatively impermeable wall that resists decolorization and is composed of peptidoglycan and secondary polymers. Gram-negatives have a thin peptidoglycan layer plus an overlying lipid-protein bilayer known as the outer membrane, which can be disrupted by decolorization. Some bacteria have walls of intermediate structure and, although they are officially classified as gram-positives because of their linage, they stain in a variable manner. One prokaryote domain, the Archaea, have such variability of wall structure that the Gram stain is not a useful differentiating tool.

Bacteria↗
PubMed1990

[Variations in the individual consumption of table salt with or without chili in food, in a community of México].

The present study was carried out in a rural community in the central plateau of Mexico, with the objective of estimating the mean daily consumption of table salt at the family and individual level, and to determine if the individual taste to salt added to the food at the table, varied with the presence or absence of a hot species, "chile", to the food. Our results showed variability in three "barrios" of the community, which go from the central, more urban-type (Temascalcingo) to an intermediate-type (Boquí), and to a more rural-type (Bonshó), showing the highest mean consumption of salt at the family level in the most urban barrio (47.2 g/day), while the mean family consumption in the other two barrios (28.2 and 33.9 g/day, respectively) was lower. At the individual level, there were differences in salt consumption associated to sex and age. The highest consumptions were found in the more urban-type barrio, in which men in the 15-22 year-old group consumed a mean of 9 g/day, and women in the 7-14 year-old group consumed a mean of 6.37 g/day. When the individual taste for salt added to foods commonly prepared in the community were studied, we found a statisticaly significant difference in individual taste associated with the presence or absence of chile in the food. In two of the study meals (breakfast and lunch) the total grams of salt added to the food which did not contain chile was significantly higher than the salt added to the food which contained chile, suggesting that the presence of the specie may account for a great part of the need to enhance food flavor. This in turn could explain the smaller consumption of table salt in the more rural-type section of the population noted in the first part of the study, in which families tend to add more chile to their food than in the urban-type settings.

Adolescent↗
PubMed1986

Pathogenesis of subclinical bovine mastitis: diagnostic and dynamic characteristics of various subclinical udder conditions monitored by means of the International Dairy Federation criteria.

This investigation, conducted on a small herd milked by machine without disinfectant teat dipping, shows that a limited population of 21 normally lactating dairy cows regularly examined at 24 h intervals during 22 consecutive days, may be used for monitoring dynamic fluctuations of udder conditions. From the results it is apparent that, on subclinical levels, udder health of dairy cows depends in principle on a variety of conditions, variability in dynamic fluctuations and the balance between persistent, deteriorating and improving health states. As health states, especially active and intermediate to the mastitic and normal condition at the opposing extremes of udder health, aseptic mastitis (AM) and latent infection (LI) cross-reacting with each other and with each of the other health states, are of particular practical interest. From the dynamic fluctuations of AM and LI it seems conceivable that the strategy of mastitis control proposed by several workers and found lacking in several respects during this investigation, may promote the shifting of abnormal udder conditions from those associated with mastitogenic infections to others of a non-bacterial, i.e. unspecific nature. In general, the data suggest that further work on the dynamics of different health states is necessary, and that it may be advantageous also to use the small herd model described for determinations on representative populations of cows selected at random from large dairy herds otherwise unsuitable for investigations on daily and other dynamic changes of udder health.

Animals↗
PubMed1980

Free radicals generation by the inflammatory cells.

One of the most impressive property of the leucocytes is that of changing the oxidative metabolism during various functions. When challenged with phagocytosable particles or with membrane perturbing agents such as chemotactic factors, detergents, lectins and other ligands, granulocytes and mononuclear phagocytes undergo a dramatic increase of oxygen consumption which is associated with the production of superoxide anion (O-2), of hydrogen peroxide (H2O2) and of hydroxyl radical (OH.). These events are referred to as "respiratory burst' . Most of the functions of the inflammatory cells (killing of micro-organisms, tissue damage, amplification of the inflammatory process) are linked to the production, to the fate and to the chemical reactivity of these highly reactive compounds. The authors examine the following aspects: (i) the mechanism responsible for the respiratory burst; (ii) the conditions present in the inflammatory site that induces the metabolic activation of leucocytes; (iii) the variability of the respiratory burst in different types of leucocytes; (iv) the fate, the interrelationships and the reactivity of the intermediate products of oxygen reduction; (v) the relationships between the inflammatory process and the production of free radicals by the inflammatory cells.

Animals↗
PubMed1998

Carotid and coronary disease: staged or simultaneous management?

Up to 12% of patients presenting for coronary bypass have critical carotid disease, and more than 50% of patients presenting for carotid endarterectomy have significant coronary disease. Patients requiring surgery for both carotid and coronary disease may be managed with carotid endarterectomy followed by coronary bypass (staged approach), with coronary bypass followed by carotid endarterectomy (reversed staged approach), or with simultaneous coronary bypass-carotid endarterectomy. There are no compelling data proving superiority of any of these three approaches. The staged approach is usually associated with lower stroke rates but higher myocardial infarction and mortality rates; the reversed staged approach with higher stroke rates but lower myocardial infarction and mortality rates; and the simultaneous approach with intermediate stroke, myocardial infarction, and mortality rates. Unfortunately, reported series vary widely in stroke and mortality rates because of wide variability in patient selection criteria, especially for simultaneous procedures. Management decisions in these patients should be based on the relative severity of their carotid and coronary lesions. Management guidelines are discussed in detail.

Carotid Artery Diseases↗
PubMed1983

Two different metabolic responses to ischaemia: inherent variability or artefact?

Guinea pig hearts, perfused with (5-3H) glucose (8 mmol . litre-1) and subjected to 30 min of reduced (6%) coronary flow, exhibited two distinctly different metabolic and electrophysiological responses to ischaemia. In 22 of the 50 hearts studied (Group 1) glucose utilisation declined during ischaemia from 2.5 +/- 0.2 to 1.3 +/- 0.2 mumol . litre-1 . g-1 dry wt. In these hearts, endogenous substrates such as glucogen and triglyceride were mobilised and, although input into glycolysis may have been initially increased through accelerated glycogenolysis, estimated glycolytic flux (1.7 +/- 0.1 mumol hexose . min-1 . g-1 dry wt) remained limited. Instead, there was a large accumulation of the intermediates of glycolysis, an increase in the content of AMP and cAMP and a particularly marked decline in creatine phosphate levels. With subsequent reperfusion, these hearts all fibrillated. In contrast, in the other 28 hearts (Group 2) glucose utilisation (5.1 +/- 0.4 mumol . min-1 . g-1 dry wt) and estimated glycolytic flux (4.1 +/- 0.01 mumol hexose . min-1 . g-1 dry wt) were increased during ischaemia. In these preparations, relatively little glycogen and triglyceride were utilised, and there was less accumulation of glycolytic intermediates. Further, lower levels of AMP and cAMP were observed and creatine phosphate: creatine ratios were better maintained. These hearts did not fibrillate during reperfusion. Thus the variable susceptibility of the myocardium to ischaemic damage, as evidenced by the random incidence of ventricular fibrillation during reperfusion, may have been related to two distinctly different metabolic responses to restricted perfusion.

Adenine Nucleotides↗
PubMed1997

A DNA cytometric proliferation index improves the value of the DNA ploidy pattern as a prognosticating tool in patients with carcinoma of the prostate.

OBJECTIVES: A still controversial issue is whether the results of a cytometric assessment of the DNA distribution pattern of the nuclei of the neoplastic parenchymal cells of a prostatic adenocarcinoma has additional prognostic value to that of the stage and grade of the disease. To increase the accuracy of the DNA ploidy assessments. Image cytometry (ICM) has been used and combined with the determination of an ICM proliferation index (PI) to increase its value as an additional prognosticating tool. METHODS: We investigated 96 patients, followed up since diagnosis in 1980/1981 until death or, in 11 surviving patients, for an average of 14.5 years. Survival analysis was made by the conventional Kaplan-Meier method. Fine-needle aspiration biopsy was used as the major diagnostic tool. The neoplastic cell nuclei were classified as ICM DNA diploid, tetraploid, or aneuploid by means of the ploidy-establishing peak in the ICM DNA histograms, as well as the fraction of tumor cells in the S-phase. Scattered cells to the right of the ploidy-establishing peak, the S-phase fraction, and those in the G2M area of the ICM DNA histograms were counted as percent of the total number of tumor cells; this percentage was defined as the PI. Arbitrarily, tumors with a PI less than 5% were classified as having a low proliferation rate, those with a PI greater than 10% were considered highly proliferating, and those with a PI between 5% and 10% as carcinomas with an intermediate proliferation potency. RESULTS: By univariate analyses, clinical stage, cytodiagnostic grade, cytometric DNA ploidy pattern and PI all had significant prognostic value. By multivariate analyses, the PI was found to add prognostic information to that of the ICM DNA ploidy pattern variable, giving it an increase in its statistical P value from 0.002 to 0.0005. As a consequence, the combination of these two variables was found to give rise to three new patient groups with regards to their prognosis: DNA group I had tumors with a diploid ICM DNA pattern with a low PI; DNA group II had tumors with a diploid or tetraploid ICM DNA tumor cell nuclei pattern with an intermediate PI; and DNA group III had a diploid or tetraploid ICM DNA pattern with high PI and all tumors with an aneuploid pattern. By multivariate analysis, including tumor grade and clinical stage, these new DNA groups (P = 0.0004) and M stage disease (P = 0.0006) were the only significant prognostic variables. CONCLUSIONS: A DNA cytometric PI improves the prognosticating value of DNA ploidy. Patients with prostatic adenocarcinomas, classified as DNA group I, have a low risk of death from their neoplastic disease with deferred or hormonal treatment only.

Adenocarcinoma↗