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At least 19 recordsLinked to original sources

Spontaneous regression of merkel cell carcinoma: a comparative study of TUNEL index and tumor-infiltrating lymphocytes between spontaneous regression and non-regression group.

Some Merkel cell carcinomas (MCC) have been reported to regress spontaneously. To clarify the mechanisms of spontaneous regression (SR) of MCC, we analyzed the TUNEL index, the labeling index of proliferating cell nuclear antigen (PCNA), the labeling index of bcl-2 protein, and the expression of p53 of the tumor cells. We also evaluated the number of infiltrating lymphocytes surrounding the tumor in the tissue specimens. Among seven patients with MCC (SR: n=4; non-regression (NR): n=3), the TUNEL index in the SR group was significantly higher than that in NR group (5.2 and 2.0%, respectively). In addition, the number of lymphocytes around the tumor nests was also significantly increased in the SR group compared to NR group (1576 and 663 cells/mm(2), respectively). Most of the infiltrating lymphocytes were UCHL-1 positive T-cells. There were no significant differences of the PCNA labeling index, the bcl-2 protein labeling index, and the expression p53 between SR and NR group. These results indicate that apoptosis and local T-cell mediated immune response might be involved in spontaneous regression of MCC.

Aged↗

Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS).

BACKGROUND: Intensive lowering of serum cholesterol may retard progression of coronary atherosclerosis in selected groups of patients. However, few data are available on the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels who undergo various forms of treatment. The Regression Growth Evaluation Statin Study (REGRESS) addresses this group of patients. METHODS AND RESULTS: REGRESS is a double-blind, placebo-controlled multicenter study to assess the effects of 2 years of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis in 885 male patients with a serum cholesterol level between 4 and 8 mmol/L (155 and 310 mg/dL) by quantitative coronary arteriography. Primary end points were (1) change in average mean segment diameter per patient and (2) change in average minimum obstruction diameter per patient. Clinical events were also analyzed. Of the 885 patients, 778 (88%) had an evaluable final angiogram. Mean segment diameter decreased 0.10 mm in the placebo group versus 0.06 mm in the pravastatin group (P = .019): The mean difference between treatment groups was 0.04 mm, with a 95% CI of 0.01 to 0.07 mm. The median minimum obstruction diameter decreased 0.09 mm in the placebo group versus 0.03 mm in the pravastatin group (P = .001): The difference of the medians between the treatment groups was 0.06 mm, with a CI of 0.02 to 0.08 mm. At the end of the follow-up period, 89% (CI, 86% to 92%) of the pravastatin patients and 81% (CI, 77% to 85%) of the placebo patients were without new cardiovascular events (P = .002). CONCLUSIONS: In symptomatic men with significant coronary atherosclerosis and normal to moderately elevated serum cholesterol, less progression of coronary atherosclerosis and fewer new cardiovascular events were observed in the group of patients treated with pravastatin than in the placebo group.

Angioplasty, Balloon, Coronary↗

Regression growth evaluation statin study (REGRESS): study design and baseline characteristics in 600 patients. The REGRESS Research Group.

OBJECTIVE: To assess the effects of lipid lowering, using a hydroxymethyl glutaryl coenzyme A reductase inhibitor (pravastatin) in symptomatic men with coronary artery disease. To assess follow-up intervention modes and baseline cardiovascular risk factors in men after routine diagnostic coronary arteriography which showed a significant stenosis (at least 50%) in a major segment. DESIGN: Baseline characteristics are stated in a multicentre, prospective, double-blind, randomized, placebo-controlled trial entitled 'regression growth evaluation statin study' (REGRESS). SETTING: Seven university hospitals and four referral hospitals in The Netherlands. PATIENTS: The baseline characteristics are given for the initial 600 patients who entered the REGRESS trial. All patients were 'normocholesterolemic' and suffered from symptomatic coronary artery disease. INTERVENTION: Initial follow-up treatment was analyzed after coronary arteriography, in accordance with standardized clinical practice (angioplasty, bypass grafting or medical management only). MAIN RESULTS: In contrast to routine procedures, 44% of the patient population was found in the medical management only stratum, whereas 32% was found in the coronary bypass graft and 24% in the percutaneous transluminal coronary angioplasty stratum. No major coronary cardiovascular risk factor could explain the decision to perform a certain follow-up intervention. Overall patients showed a low serum high density lipoprotein (HDL) cholesterol level. A higher New York Heart Association classification for anginal complaints tended to favour a more aggressive follow-up approach. CONCLUSIONS: The total REGRESS population showed relatively low HDL cholesterol blood levels compared with the general Dutch population. The rationale to perform a specific follow-up intervention by the treating cardiologist is unclear. Severity of anginal complaints may lead to a more active intervention procedure.

Aged↗

A study of atherosclerosis regression in Macaca mulatta: III. Chemical changes in arteries from animals with atherosclerosis induced for 19 months and regressed for 48 months at plasma cholesterol concentrations of 300 or 200 mg/dl.

The influence of two levels of plasma cholesterol concentration on the long-term regression of atherosclerotic plaques in rhesus monkeys (Macaca mulatta) was studied. Forty-eight young adult male rhesus monkeys were fed an atherogenic diet for 19 months, then diets designed to maintain plasma cholesterol concentrations at 280-320 mg/dl (actual 316 +/- 10 mg/dl; mean +/- SEM) of 180-220 mg/dl (actual 204 +/- 4 mg/dl). Twelve animals were killed after 19 months to evaluate the atherosclerosis produced. The remaining 36 monkeys were studied after 48 months of atherosclerosis regression. Significantly greater amounts of accumulated nonesterififed and esterified cholesterol were lost from the arteries of monkeys that underwent regression at about 200 mg/dl, in comparison with 300 mg/dl. Regression at both plasma cholesterol concentrations resulted in increased collagen and decreased elastin content in the thoracic aorta but not in the other arteries studied. After regression at 300 mg/dl there was no change (83%) in the frequency of calcification of the thoracic aorta, while at 200 mg/dl the frequency of calcification was reduced to 50%. When compared with monkeys whose athersclerotic lesions were produced in an identical manner but were regressed for only 24 months, after 48 months had increased cholesterol concenrations in the thoracic aorta and carotid artery but not the abdominal aorta of iliaco-femoral artery, regardless of the plasma cholesterol concentration. The lipid composition of the regressed plaque suggested a change in plaque lipid toward the character of extracellular deposits described physically as crystalline in nature. The physical state was influenced by the length of the regression period and the plasma cholesterol concentration during regeression. In the thoracic aorta, principally as a result of changes in elastin content, the collagen-to-elastin ratio increased between 24 and 48 months of regression. It is proposed that the differences in removal of cholesterol from the thoracic and abdominal aorta after 24 and 48 months of regression in animals at 300 mg/dl may be influenced by the rearrangement of connective tissue. On the basis of the lipid and mineral content of uncomplicated atherosclerotic plaques after 4 yers of regression, it appears that the plasma cholesterol concentration during the regression period is a signigicant factor influencing the extent of plaque regression as well as the potential for further progression.

Animals↗

Adjustment for regression dilution in epidemiological regression analyses.

PURPOSE: The term "regression dilution" describes the dilution/attenuation in a regression coefficient that occurs when a single measured value of a covariate is used instead of the usual or average value over a period of time. This paper reviews the current knowledge concerning a simple method of adjusting for regression dilution in single and multiple covariate situations and illustrates the adjustment procedure. METHODS: Formulation of the regression dilution problem as a measurement error problem allows existing measurement error theory to be applied to developing methods of adjustment for regression dilution. This theory leads to a precise method of adjustment for linear regression and approximate methods for logistic and Cox proportional hazards regression. The method involves obtaining the naive estimates of coefficients by assuming that covariates are not measured with error, and then adjusting these coefficients using reliability estimates for the covariates. Methods for estimating the reliability of covariates from the reliability and main study data and a method for the calculation of standard errors and confidence intervals for adjusted coefficients are described. RESULTS: An illustration involving logistic regression analysis of risk factors for death from cardiovascular disease based on cohort and reliability data from the Busselton Health Study shows that the different methods for estimating the adjustment factors give very similar adjusted estimates of coefficients, that univariate adjustment procedures may lead to inappropriate adjustments in multiple covariate situations, whether or not other covariates have intra-individual variation, and when the reliability study is moderate to large, the precision of the estimates of reliability coefficients has little impact on the standard errors of adjusted regression coefficients. CONCLUSIONS: The simple method of adjusting regression coefficients for "regression dilution" that arises out of measurement error theory is applicable to many epidemiological settings and is easily implemented. The choice of method to estimate the reliability coefficient has little impact on the results. The practice of applying univariate adjustments in multiple covariate situations is not recommended.

Analysis of Variance↗

Regression of papillomas induced by cottontail rabbit papillomavirus is associated with infiltration of CD8+ cells and persistence of viral DNA after regression.

Cottontail rabbit papillomavirus (CRPV) is a highly oncogenic papillomavirus and has been successfully used as a model to develop protective vaccines against papillomaviruses. Papillomas induced by the virus may spontaneously regress, suggesting that CRPV can also serve as a model to develop therapeutic vaccines. As a first step toward this goal, we have analyzed immunologic and viral aspects associated with papilloma regression and have identified several features unique to regression. Immunohistochemical staining of biopsies from growing and regressing papillomas and from sites after complete regression showed infiltration of CD8+ cells into the basal and suprabasal layers of the epidermis only during active regression. In situ hybridizations with mRNA-specific probes were strongly positive for E6 and E7 mRNAs during regression, but no late mRNA was present. Viral DNA was detected by in situ hybridization during regression but not after regression. However, analysis by PCR revealed persistence of viral DNA for several months at the majority of regression sites. The results suggest that stimulation of a strong CD8+ response to virus-infected cells is important for an effective therapeutic vaccine and that special attention should be given to the suppression of latent infection.

Animals↗

[Research of myopia development in children with self-regression of retinopathy of prematurity and in children with regression after cryotherapy].

PURPOSE: The aim of the paper is to estimate the influence of self-regression of retinopathy of prematurity (ROP) and regression after cryotherapy for development of axial myopia in premature babies. MATERIAL AND METHODS: The researches concerned 4 groups of premature babies in the 6th, 12th and 24th month of life. Group 1--without ROP, group 2--with self-regression of ROP, group 3--with regression of ROP after cryotherapy and group 4--with one eye with self-regression of ROP and second eye with regression after cryotherapy. RESULTS: In the 6th and 24th month of life mean axial length of eyeball in children from group 3 was statistically significantly higher than mean axial length of eyeball in children from group 1 and 2. In the 12th month of life mean axial length of eyeball in children from group 3 was statistically significantly higher than mean axial length of eyeball in children from group 1. In group 4 mean axial length of eyeball with regression of ROP after cryotherapy was statistically significantly higher than mean axial length of eyeball with self-regression of ROP. CONCLUSIONS: Self-regression of ROP and regression of ROP after cryotherapy may cause development of axial myopia in premature babies.

Child, Preschool↗

Cyclic angiogenesis and blood vessel regression in the ovary: blood vessel regression during luteolysis involves endothelial cell detachment and vessel occlusion.

Angiogenesis occurs as a cyclically regulated process in the ovary and the uterus. After ovulation, there is massive sprouting of blood vessels in the growing corpus luteum (CL) during the first third of the ovarian cycle. During luteolysis and for several weeks thereafter, all newly formed vessels regress. Here we have systematically analyzed regression of blood vessels during luteolysis to identify mechanisms of blood vessel regression. Blood vessel counts are highest in the midcycle CL and drop rapidly after the onset of luteolysis. After a rapid phase of tissue dissociation, blood vessel regression proceeds slowly over several weeks in the residual CL. Endothelial cells in regressing vessels acquire a distinctly rounded and condensed phenotype. Ultrastructural analysis of blood vessel regression processes in the cyclic CL suggests two major mechanisms of blood vessel regression: a) detachment of rounded endothelial cells from their basement membrane, leaving areas devoid of covering endothelial cell monolayer, and b) contraction and occlusion of arterioles and small arteries with pronounced proliferation of smooth muscle cells. In situ detection of nucleosomal fragmentation products demonstrates numerous apoptotic luteal cells, but only a few apoptotic endothelial cells in the regressing CL. Induction of apoptosis in cultured endothelial cell monolayers by RGD peptides demonstrated that endothelial cells detach from their adhesive surface before fully becoming positive for nucleosomal fragmentation products. These data indicate that cyclic angiogenic processes in the ovary offer a suitable experimental system to analyze mechanisms of blood vessel growth and regression, and suggest that detachment of endothelial cells before apoptosis as well as contractive occlusion of blood vessels may be critical determinants of blood vessel regression.

Animals↗

Spontaneous regression of Friend-virus-induced erythroleukemia. VII. The genetic control of regression.

The genetic control of spontaneous regression of erythroleukemia was studied in parental and hybrid mice in which leukemia was induced by the regressing strain of Friend virus (RFV). Because in previous studies parental regressor mouse strains tested (N/PLCR, SIM, NIH Swiss) all had the FV-1n/n genotype and the progressor mouse strains (SIM.R, BALB/c) had the Fv-1b/b genotype, we detemined the influence of Fv-1 alleles on regression. Genes which influence regression were dominant and had partial penetrance in (progressor x regressor) F1 mice. Regression occurred in hybrid mice which inherited the Fv-1b/b genes of each of the progressor mouse strains. Regression and Fv-1 alleles also segregated independently in (N/PLCR x BALB/c) F2 mice, in random-bred Swiss mice heterozygous for the Fv-1 gene, in partially inbred Swiss recombinant progressor and regressor mouse lines, and in hybrid mice carrying the Fv-1b/b gene of SIM.R mice. Regressor SIM and progressor SIM.R mice, which were bred to be congeneic at the Fv-1 locus, also differ with respect to recovery from viremia, suggesting that their Rfv-3 genes differ and influence regression. Crosses of SIM and SIM.R mice with the A.BY (Rfv-3s/s) mouse strain confirmed that SIM and SIM.R carry Rfv-3r/r and Rfv-3s/s, respectively. We conclude that Fv-1b/b is not inhibitory to regression nor is the Fv-1 gene a genetic deteminant in the process. The data suggest that regression is influenced by several genes, including those (Rfv-1, Rfv-2, Rfv-3) shown to affect recovery from leukemia in other systems.

Alleles↗

Regression analysis when covariates are regression parameters of a random effects model for observed longitudinal measurements.

We consider regression analysis when covariate variables are the underlying regression coefficients of another linear mixed model. A naive approach is to use each subject's repeated measurements, which are assumed to follow a linear mixed model, and obtain subject-specific estimated coefficients to replace the covariate variables. However, directly replacing the unobserved covariates in the primary regression by these estimated coefficients may result in a significantly biased estimator. The aforementioned problem can be evaluated as a generalization of the classical additive error model where repeated measures are considered as replicates. To correct for these biases, we investigate a pseudo-expected estimating equation (EEE) estimator, a regression calibration (RC) estimator, and a refined version of the RC estimator. For linear regression, the first two estimators are identical under certain conditions. However, when the primary regression model is a nonlinear model, the RC estimator is usually biased. We thus consider a refined regression calibration estimator whose performance is close to that of the pseudo-EEE estimator but does not require numerical integration. The RC estimator is also extended to the proportional hazards regression model. In addition to the distribution theory, we evaluate the methods through simulation studies. The methods are applied to analyze a real dataset from a child growth study.

Bias↗

Theoretical and technical comments on regression and anti-regression.

Following a discussion of the 'classical' formulations on regression and fixation, the view is put forward that the distinction between various types of regression is on the whole superfluous. However, it is important to distinguish between 'latent' regression in the patient's 'present unconscious', the contents of which are defended against and kept from consciousness on the one hand, and 'manifest' regression on the other, in which current versions of developmentally earlier wishes and fantasies emerge overtly in acceptable form in thought and behaviour. The anti-regressive function can be regarded as being operative from early in development, and functions to a greater or lesser extent throughout our daily lives. As a concept it reflects the operation of all the defence mechanisms and manoeuvres which operate to protect consciousness and conscious awareness of behaviour. Because it reflects a general tendency of the mind to defend consciousness from unwelcome content arising in the present unconscious, it is consequently a major source of resistance in analysis. Analytic progress takes place when the patient gains sufficient security in an analysis-syntonic way to allow a progressively increasing capacity for controlled relaxation of the anti-regressive function to take place, and for previously unacceptable wishful phantasies to be tolerated and accepted by the patient. This relaxation of the anti-regressive function is allied to Ernst Kris's description of 'regression in the service of the ego'.

Awareness↗

Retro-regression--another important multivariate regression improvement.

We review the serious problem associated with instabilities of the coefficients of regression equations, referred to as the MRA (multivariate regression analysis) "nightmare of the first kind". This is manifested when in a stepwise regression a descriptor is included or excluded from a regression. The consequence is an unpredictable change of the coefficients of the descriptors that remain in the regression equation. We follow with consideration of an even more serious problem, referred to as the MRA "nightmare of the second kind", arising when optimal descriptors are selected from a large pool of descriptors. This process typically causes at different steps of the stepwise regression a replacement of several previously used descriptors by new ones. We describe a procedure that resolves these difficulties. The approach is illustrated on boiling points of nonanes which are considered (1) by using an ordered connectivity basis; (2) by using an ordering resulting from application of greedy algorithm; and (3) by using an ordering derived from an exhaustive search for optimal descriptors. A novel variant of multiple regression analysis, called retro-regression (RR), is outlined showing how it resolves the ambiguities associated with both "nightmares" of the first and the second kind of MRA.

Journal Article↗

Immunocytochemical analysis of the cellular infiltrate in primary regressing and non-regressing malignant melanoma.

Spontaneous regression occurs in a small proportion of malignant melanomas, and it is important to understand the processes involved in its induction as this may give a guide to future therapies for this disease. We have examined 36 primary malignant melanomas (19 regressing, 17 non-regressing) and identified the cellular phenotypes and activation states of the cells infiltrating regressing and non-regressing primary melanomas by immunochemistry. We have found a significantly increased number of CD3-positive cells and an increased ratio of CD4/CD8-positive cells infiltrating regressing compared to non-regressing tumors. In addition, the expression of the interleukin 2 receptor, an activation marker for T cells, was increased. However, there were no significant differences in class II MHC, CD1, intercellular adhesion molecule 1 (ICAM1), or melanoma-associated differentiation-antigen expression in these tumors. These data are consistent with melanoma regression being induced by activated CD4 T cells and do not seem to be related to the differentiation markers we have examined on these tumors.

Antibodies, Monoclonal↗

A study of atherosclerosis regression in Macaca mulatta. V. Changes in abdominal aorta and carotid and coronary arteries from animals with atherosclerosis induced for 38 months and then regressed for 24 or 48 months at plasma cholesterol concentrations of 300 or 200 mg/dl.

Young adult male rhesus monkeys (Macaca mulatta) were fed an atherogenic diet for 38 months. After 38 months of atherosclerosis induction, a baseline group was selected and necropsied to determine the extent and severity of atherosclerosis before regression regimens were begun. The remaining animals were fed diets that varied in cholesterol concentration in order to maintain plasma cholesterol concentrations of approximately 200 or 300 mg/dl for either 24 or 48 months. The progression or regression of atherosclerosis in coronary arteries, abdominal aorta, and carotid arteries was determined by comparing them to the baseline group. Coronary artery atherosclerosis regressed in the majority of animals after 4 years but not after 2 years when plasma cholesterol concentrations were about 200 mg/dl. Among the animals maintained at plasma cholesterol concentrations of about 300 mg/dl, about half the animals progressed in the extent of coronary artery atherosclerosis while about half regressed. The majority of the animals that progressed in lesion extent were genetic hyperresponders to dietary cholesterol whereas those that regressed were predominantly hyporesponders, even though their plasma lipid concentrations were equivalent during the regression phase. The changes seen in atherosclerosis extent in the abdominal aorta were quite similar to the changes seen in coronary arteries. Changes at this site were not pronounced after 2 years, but after 4 years animals with plasma cholesterol concentrations of about 300 mg/dl progressed while the animals at 200 mg/dl were mostly unchanged. No evidence for atherosclerosis regression was found in the common carotid arteries or in the carotid bifurcations.

Animals↗

Regressive eye movements and sentence parsing: on the use of regression-contingent analyses.

Altmann, Garnham, and Dennis (1992) recently advocated the use of a regression-contingent analysis in eye movement studies dealing with parsing of sentences containing temporary structural ambiguities. Using experimental sentences preceded by referentially supportive contexts, they demonstrated a different pattern of results when regressive eye movements were eliminated from the data set than when regressions were included. The regression-contingent analysis that they used involves an implicit assumption that regressive eye movements are a necessary consequence of subjects' being garden pathed. We report some data which demonstrate that garden path effects are sometimes even stronger in the absence of regressions and, thus, argue that readers can be garden pathed without making regressions.

Attention↗

Spontaneous regression of Friend virus-induced erythroleukemia. II. regression of Friend murine leukemia virus-induced lymphocytic leukemia.

We characterized several aspects of spontaneous regression of lymphocytic leukemia in mice. The disease, induced by the helper murine leukemia virus (MuLV) component obtained from the regressing Friend virus complex (RFV), was characterized by spleen and lymph node enlargement, thymus involvement, and anemia. Leukemia regression occurred in about 25% of infected mice and resulted in the return of lymphoid organs to near-normal weight and normal histology and the recovery from anemia. A tenfold to 1,000-fold decrease in virus titer was seen in those mice in which leukemia regressed when compared to leukemic animals, although infectious virus was still recoverable from apparently normal spleens. The sera of mice in which leukemia regressed contained potent virus-neutralizing activity that was associated mainly with immunoglobulins. These studies firmly supported the evidence that the regressing phenotype of RFV was due to its helper MuLV component (MuLV-RF).

Animals↗

Spontaneous regression of Friend virus-induced erythroleukemia. VI. Structural and antigenic differences between the regressing and conventional strains of virus.

The regressing and conventional strains of Friend virus were compared by neutralization assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and tryptic peptide mapping of the individual viral components. Neutralization rates of the two viruses differed in the presence of monospecific anti-gp70 antiserum and sera from regressed or immunized mice. Neutralization of regressing Friend virus, but not conventional Friend virus, occurred when the viruses were incubated with anti-p15(E) and complement. Human serum inactivated conventional Friend virus more rapidly than regressing Friend virus, probably as a result of virolysis induced by the reaction of viral p15(E) with human complement component C1. Structural differences between the viruses were detected in their gp70 viral glycoproteins and p15(E) and p12 proteins. Analysis of different stocks and clonal isolates of the viruses showed that the differences between the gp70 and p15(E), but not the p12 proteins, were associated with the regressing phenotype of the regressing strain of Friend virus.

Animals↗

Advanced statistics: linear regression, part II: multiple linear regression.

The applications of simple linear regression in medical research are limited, because in most situations, there are multiple relevant predictor variables. Univariate statistical techniques such as simple linear regression use a single predictor variable, and they often may be mathematically correct but clinically misleading. Multiple linear regression is a mathematical technique used to model the relationship between multiple independent predictor variables and a single dependent outcome variable. It is used in medical research to model observational data, as well as in diagnostic and therapeutic studies in which the outcome is dependent on more than one factor. Although the technique generally is limited to data that can be expressed with a linear function, it benefits from a well-developed mathematical framework that yields unique solutions and exact confidence intervals for regression coefficients. Building on Part I of this series, this article acquaints the reader with some of the important concepts in multiple regression analysis. These include multicollinearity, interaction effects, and an expansion of the discussion of inference testing, leverage, and variable transformations to multivariate models. Examples from the first article in this series are expanded on using a primarily graphic, rather than mathematical, approach. The importance of the relationships among the predictor variables and the dependence of the multivariate model coefficients on the choice of these variables are stressed. Finally, concepts in regression model building are discussed.

Bias↗