Multiple myeloma--recent developments in molecular and cellular biology.
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Aneuploidy↗
Biomedical subjects
R Hoover
Publications and source records attributed to R Hoover.
Biological aspects of multiple myeloma.
Although considerable progress has been made towards understanding many aspects of myeloma, the myeloma stem cell and the factors that drive the disease remain elusive. Recent developments in the molecular analysis of clonality have helped to confirm the presence of pre-switch B cells that are of the same clone as the myeloma plasma cells. The role of these cells in myelomagenesis has not been demonstrated, and the isotypic heterogeneity of the clonally-relevant cells suggests that the pre-switch B cells are pre-malignant progenitors of the tumour cells. Thus, the circulating clonal B cells appear to be the earliest progenitors of the mature, monoclonal plasma cells. IL-6, and possibly other cytokines, are involved in driving this process. The role of IL-6 in myeloma is complex and more involved than its proposed growth factor function. In the absence of IL-6, dependent cells become apoptotic. Increased IL-6 signalling also leads to apoptosis of myeloma cells, possibly as a result of terminal differentiation. In the presence of exogenous IL-6, the IL-6 receptor appears to be the rate-limiting factor in the pathway's activity. IL-6 may regulate the survival of myeloma cells by stimulating c-myc transcription, possibly from the P0 promoter. The high levels of c-myc transcripts and protein could regulate myeloma cell proliferation and apoptotic death by controlling p53 expression and, through it, the expression of the Rb and BAX genes. Proliferative signalling in myeloma cells is likely to be intrinsic, within the tumour cell compartment. Molecules such as CD28 and B7, both expressed by less mature myeloma cells, could represent one such self-self stimulatory mechanism, with IL-6, possibly through stimulation of c-myc expression, providing the signals for survival and differentiation.
B7-1 Antigen↗
Endothelium as an endocrine organ.
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Animals↗
Effect of heat-moisture treatment on the structure and physicochemical properties of cereal, legume, and tuber starches.
Native wheat, oat, lentil, yam, and potato starches were heat treated at 100 degrees C for 16 h at moisture contents between 10 and 30%. The heat treatment did not change granule size and shape. In oat starch, granules were less compactly packed after heat treatment. The X-ray diffraction intensities increased in wheat, oat, and lentil starches, but decreased in potato and yam. The X-ray patterns of wheat and oat starches remained unchanged, while those of lentil, potato, and yam starches became more cereal-like. In all starches, the swelling factor and amylose leaching decreased, being more pronounced in potato. Heat treatment induced complex formation between amylose and native lipids. Differential scanning calorimetry of the heat-treated samples showed a broadening of the gelatinization-temperature range and a shifting of the endothermal transition towards higher temperatures. These changes were more pronounced in potato starch. The gelatinization enthalpy of wheat, oat, and lentil starches remained unchanged, but those of potato and yam starches decreased on heat treatment. Heat treatment increased the 95 degrees C viscosity of wheat starch, but decreased those of oat lentil, potato, and yam starches. In all starches, thermal and shear stability increased after heat treatment. Acid hydrolysis decreased on heat treatment of wheat and lentil starches, but increased in oat, potato, and yam starches. However, in potato and yam starches, the foregoing trend was evident only during the first seven days of hydrolysis. Thereafter, acid hydrolysis was more pronounced in native than in heat-treated starches. The susceptibility towards hydrolysis by porcine pancreatic alpha amylase decreased on heat treatment of wheat and lentil starches, whereas increases were observed for oat, potato, and yam starches. The results indicated that the extent of starch-chain associations within the amorphous regions and the degree of crystalline order are altered during heat-moisture treatment. The magnitude of these changes were found to be dependent upon the moisture content during heat treatment and on the starch source.
Amylose↗
An approach to studies of cancer subsequent to clusters of chronic fatigue syndrome: use of data from the Nevada State Cancer Registry.
Chronic fatigue syndrome (CFS) has been increasingly associated with immune dysregulation, including depressed natural killer cell activity; this phenomenon is associated with increased susceptibility to cancer. Although anecdotal reports have suggested an association between CFS and cancer, particularly non-Hodgkin's lymphoma and brain cancer, there has been no a priori justification for evaluating such an association and no consideration of relevant parameters, such as length of latent period vs. tumor type. We reviewed data from the Nevada State Cancer Registry subsequent to a reported outbreak of a CFS-like illness in Nevada that occurred during 1984-1986. We concentrated on non-Hodgkin's lymphoma and brain/CNS tumors, with particular emphasis on persons 15-34 and 35-54 years of age. An upward trend in the incidence of brain/CNS tumors, which could be related to a national upward trend for this disease, was noted. No consistent trends were noted for non-Hodgkin's lymphoma. Because of the difficulties inherent in studies of cancer subsequent to various exposures, we evaluated the methodology for determining an association between outbreaks of CFS-like disease and cancer. We propose several approaches that should be considered in future studies for investigation of possible associations between CFS and cancer, including expected latent periods for specific tumors.
Adolescent↗
Dietary patterns associated with a low-fat diet in the national health examination follow-up study: identification of potential confounders for epidemiologic analyses.
To identify systematically the nutrient and food group intakes associated with a low-fat diet, the authors used the detailed dietary information collected from 10,306 individuals aged 32-86 years in the 1982-1984 National Health Epidemiologic Follow-up Study. Intakes of vitamin C and percentages of calories from carbohydrates, dietary fiber, poultry, low-fat dairy products, fruits, vegetables, cereals, and whole grains were markedly higher, while intakes of protein, total fat, saturated fat, oleic and linoleic acids, cholesterol, sodium, all red meats, high-fat dairy products, eggs, nuts, white bread, fried potatoes, desserts, fats, and oils were much lower in the quartile with the lowest percentage of calories from fat. These dietary patterns associated with a low-fat diet were essentially constant across strata of age, sex, race, and socioeconomic status. This study suggests that individuals on a low-fat diet substitute certain carbohydrate-rich foods such as fruits and vegetables for fat. Given these associations between low-fat diets and other dietary factors independently associated with certain cancers, these dietary factors should be considered potential confounders in studies of dietary fat and these cancers.
Adult↗
Incidence of cancer among patients with rheumatoid arthritis.
BACKGROUND: To evaluate hypotheses about the relationship between immune alterations and cancer, several investigators have determined cancer incidence in groups of patients with rheumatoid arthritis (RA), a chronic autoimmune disease. The primary finding has been an increased risk of hematopoietic cancers. PURPOSE: In this study, we have attempted to refine estimates of the association between RA and subsequent development of specific cancers. METHODS: We investigated site-specific cancer risk associated with RA in a population-based cohort study of 11683 Swedish men and women with a hospital (inpatient) diagnosis of RA. These case patients were identified from 1965 to 1983 and had follow-up through 1984 by computer linkage of the Swedish Hospital Inpatient Register to the National Swedish Cancer Registry (840 case patients with cancer) and the Swedish Registry of Causes of Death. Cancer risk was estimated by standardized incidence ratios (SIRs) for specific cancers. RESULTS: For men and women overall, there were decreased risks for cancers of the colon (SIR = 0.63; 95% confidence interval [CI] = 0.5-0.9), rectum (SIR = 0.72; 95% CI = 0.5-1.1), and stomach (SIR = 0.63; 95% CI = 0.5-0.9) and an increased risk for lymphomas (SIR = 1.98; 95% CI = 1.5-2.6). CONCLUSIONS: The reduced risk for colorectal cancer in patients with RA is consistent with previous studies of RA patients and with reports which state that use of nonsteroidal anti-inflammatory drugs may protect against the development of large bowel cancers. The excess of lymphomas also confirms a number of earlier investigations of RA patients.
Arthritis, Rheumatoid↗
Hormone replacement therapy and breast cancer mortality in Swedish women: results after adjustment for 'healthy drug-user' effect.
No change of breast cancer mortality has been reported previously after long-term hormone replacement therapy. A conceivable explanation for the apparent discrepancy between incidence and mortality may be selection bias due to lower prevalence of breast cancer in women who receive replacement hormones, compared with nonexposed women. We used a new approach to correct for bias due to this 'healthy drug-user effect,' by adjusting the external, population-based, mortality rates for such cases prevalent during the recruitment period of our cohort. In this cohort of some 23,000 Swedish women, who were prescribed various hormone replacement regimens, breast cancer mortality was analyzed after follow-up to 12 years. External analyses revealed overall standardized mortality ratios for breast cancer rising from 0.71 to 0.81, but not significantly different from unity, after adjustment procedures. In multivariate regression models, excluding prevalent cases in the cohort, women prescribed estradiol, conjugated estrogens, or an estrogen-progestin combination were not at a higher risk relative to those given other and weak estrogens, relative risks being 0.81 and 0.68, respectively. On the basis of the present analytical approach, we conclude that breast cancer mortality does not appear to be changed overall or in subgroups, despite increased incidence.
Aged↗
Combined oestrogen-progestogen replacement and breast cancer risk.
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Breast Neoplasms↗
Does chronic fatigue syndrome predispose to non-Hodgkin's lymphoma?
Chronic fatigue syndrome, an illness that frequently is associated with abnormalities of cellular immunity, has been reported anecdotally to be associated with an increased incidence of lymphoid hyperplasia and malignancy. This report describes an initial analysis of population-based cancer incidence data in Nevada, focusing on the patterns of non-Hodgkin's lymphoma prior to and subsequent to well described, documented outbreaks of chronic fatigue syndrome during 1984-1986. In a study of time trends in four age groups, the observed time trends were consistent with the national trends reported in the Surveillance, Epidemiology, and End Results Program. No statistically significant increase attributable to the chronic fatigue syndrome outbreak was identified at the state level. Additional studies are in progress analyzing the data at the country level, reviewing patterns in other malignancies, and continuing to monitor the cancer patterns over subsequent years.
Adolescent↗
Adhesion to and invasion of cultured human cells by Bartonella bacilliformis.
Bartonella bacilliformis was tested for its ability to adhere to and invade tissue culture cell monolayers. The parasite was able to efficiently bind and penetrate human dermal fibroblasts, human laryngeal epithelium, and human umbilical vein endothelial cells. Exposure of the organism to immune serum prepared against a crude Bartonella extract containing cell wall and membranous material resulted in decreased ability of the parasite to invade host cells. There was also an overall reduction in the invasiveness of bartonellae and total host cell association when human laryngeal epithelial cells and human umbilical vein endothelial cells were preexposed to cytochalasin D, indicating an active involvement of host cells in the uptake of bartonellae. Transmission electron microscopy revealed the presence of bartonellae inside and outside intracellular vacuoles. These data suggest that a surface-associated factor is involved in the invasion process and that internalization of the parasite by host cells involves a microfilament-dependent process similar to phagocytosis.
Adhesins, Bacterial↗
Endotoxin enhancement of lymphocyte adherence to cultured sheep lung microvascular endothelial cells.
The most common predisposing factor for development of the adult respiratory distress syndrome is gram-negative sepsis. Our previous studies have shown that a single infusion of Escherichia coli endotoxin into sheep causes early sequestration of lymphocytes in the lungs' microcirculation. In this report, we examined the effects of endotoxin on sheep lymphocyte adherence to sheep pulmonary microvascular endothelial cells in vitro. Endothelial cells were exposed to endotoxin, and subsequent adherence of 51Cr-labeled lymphocytes was measured in a monolayer adhesion assay. Endotoxin enhanced adherence of lymphocytes isolated from blood and caudal mediastinal node (CMN) lymph in a time- and dose-dependent manner. Adherence of CMN lymphocytes increased from a control value of 13.6 +/- 1.6% to 29.9 +/- 3.1% after 4 h of treatment with 1 microgram/ml endotoxin. Both B and T lymphocytes contributed to the increased adherence. Pretreatment of the endothelial cells with cycloheximide revealed that the endotoxin-enhanced adherence was partially dependent upon protein synthesis. Morphologic studies revealed that enhanced adherence was accompanied by a 5-fold increase in migration of lymphocytes between endothelial cells. In contrast to human umbilical vein endothelial cells, antibodies to the known lymphocyte adherence molecules, lymphocyte function-associated antigen (LFA-1), CD-44, and the lymphocyte homing receptor (LECAM-1), were ineffective in blocking adherence to the sheep pulmonary endothelial cells. We conclude that the acute sequestration of lymphocytes in the pulmonary microcirculation of sheep after endotoxin administration is due to increased adhesive properties of the endothelial cells. Our data suggest that this adherence is mediated by as yet undescribed mechanisms that may be unique to pulmonary microvascular endothelium.
Animals↗
The debrisoquine metabolic phenotype and DNA-based assays: implications of misclassification for the association of lung cancer and the debrisoquine metabolic phenotype.
Debrisoquine is an antihypertensive drug that is metabolized by cytochrome P4502D6. Deficient metabolism is inherited as an autosomal recessive condition. We previously reported in a case-control study that extensive metabolizers of debrisoquine were at greater risk of lung cancer compared to poor and intermediate metabolizers. Cloning of the gene that encodes P4502D6 (CYP2D6) led to the identification of both wild-type and mutant forms of the gene. Subsequently, a DNA-restriction fragment length polymorphism (RFLP) was identified, and a Southern hybridization-based test was developed in an attempt to define the genotype. When the DNA-RFLP test was applied to stored DNA from our study subjects there was neither a significant association with the metabolic phenotype nor an association with lung cancer. Further work has demonstrated that the wild-type gene, which was characterized by a 29-kb allele, can also contain mutations that result in nonfunctional or absent proteins. When these mutations are present, individuals exhibit the poor or intermediate metabolizer phenotype in spite of the presence of the 29-kb putative wild-type allele. Sequence determination of the mutants led to the development of techniques to exploit the polymerase chain reaction, which, together with Southern analysis, have been reported to detect as many as 95% of poor metabolizers. This technique is being used to examine the association of the extensive metabolizer genotype with lung cancer in the subjects from the case-control study. Preliminary results indicate a weak association between the homozygous wild-type genotype and lung cancer; in contrast, the extensive metabolizer phenotype is strongly associated with lung cancer in this subset.(ABSTRACT TRUNCATED AT 250 WORDS)
Case-Control Studies↗
Modulation of membrane cholesterol levels: effects on endothelial cell function.
The endothelial cell lining of blood vessels is now recognized as an active interface between blood and the underlying tissue. Modulation of cholesterol levels in several cell types has resulted in altered cell function. We have removed cholesterol from the endothelial cell membrane and have observed corresponding alterations in endothelial cell function. Following depletion of cholesterol from the endothelial cells, polymorphonuclear leukocyte adhesion to the cells was decreased. Angiotensin-converting enzyme activity of the endothelial cells was increased following removal of cholesterol from the endothelial cell membranes. The results of fluorescence polarization measurements suggest that these changes may be partially explained by altered membrane order.
Animals↗
Composition, structure, functionality, and chemical modification of legume starches: a review.
The major carbohydrate of the legume seed is starch, which represents up to 45% of the total seed weight. In recent years, substantial progress has been made in understanding the relationship between starch structure and functionality. However, these studies have been mainly on cereal and tuber starches. The present status of knowledge on the composition, structure, functionality, digestibility, and chemical modification of legume starches is reviewed. In addition present concepts of granule structure, gelatinization, retrogradation, and rheology are also reviewed. Future research needs in the area of legume starch chemistry are discussed.
Fabaceae↗
Linking the elderly to community services.
Sometimes, the only contact elderly patients have with outside medical services is through the EMS network. Find out how one city uses prehospital providers to link these patients with community services tailored to their needs.
Aged↗
Survival in women receiving hormone replacement therapy. A record-linkage study of a large population-based cohort.
Survival was studied in a population-based cohort of over 23,000 women who were prescribed hormone replacement therapy. Complete follow-up through 1986 revealed a total of 1472 deaths, which was somewhat lower than expected; the relative survival being 101.1% (95% CL, 100.8, 101.3) after 5 years and 102.4% (95% CL, 101.9, 102.8) after 10 years. The relative survival increased with increasing age at entry into the cohort, being 98.2% (95% CL, 96.6, 99.8) in the 40-44 and 105.2% (95% CL, 101.4, 109.1) in the 65-69 year age group after 10 years. Neither the type of compound (potent vs non-potent estrogens), nor the year of entry into the cohort seemed to affect survival, whereas survival advantage generally increased with years of follow-up. Multivariate analysis showed that age at time of first prescription was the only determinant that significantly affected the death risk. This pattern could be explained by confounding due to selection of healthy subjects receiving hormone replacement therapy and/or by the specific choice of estrogen compounds (and progestogens), related to age. It is concluded that hormone replacement therapy is associated with a survival which is similar to or--notably at ages above 50-60 years--slightly higher than that in the general population.
Adult↗
Risk of cancer in women receiving hormone replacement therapy.
Cancer risk following treatment with non-contraceptive estrogens was studied in a population-based cohort of 23,244 women. Complete follow-up for an average of 6.7 years revealed 1,087 incident cancers versus 962.5 expected (relative risk/RR/ = 1.13; 95% confidence interval 1.10-1.20). We confirmed the recent findings of a more detailed analysis of the same cohort, based on a 1-year shorter follow-up period, namely: a markedly increased risk of endometrial cancer (RR = 1.8; 1.5-2.1), notably in women receiving potent estrogens, i.e., conjugated estrogens or estradiol (RR = 2.0; 1.6-2.4), and a slightly increased risk of breast cancer (RR = 1.1; 1.0-1.2). A slightly decreased risk of invasive cervical cancer (RR = 0.8; 0.5-1.2) is most likely due to more frequent smear taking than in the background population. There was no increase in the risk of cancer of ovary (RR = 1.0; 0.8-1.2), pancreas (RR = 0.8; 0.5-1.2), large bowel (RR = 1.0; 0.8-1.2) or kidney (RR = 1.0; 0.7-1.4). The risk of developing cancer in liver or biliary tract was lower than expected (RR = 0.4; 0.2-0.7), particularly in women who had used potent estrogens (RR = 0.3; 0.1-0.6), an unexpected finding which warrants further studies. Increased risks of malignant melanoma (RR = 1.5; 1.0-2.1) and lung cancer (RR = 1.3; 0.9-1.7) need cautious interpretation because of their low magnitude, the absence of a biological gradient when subgroups were analyzed and the slightly higher prevalence of smokers in the cohort than in the background population.
Climacteric↗