Delayed hypersensitivity reactions to diclofenac.
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Aged↗
Biomedical subjects
I D Bassukas
Publications and source records attributed to I D Bassukas.
[Regression phase as therapeutic goal of cryosurgical treatment of growing capillary infantile hemangiomas. Treatment decision, treatment strategy and results of an open clinical study].
BACKGROUND AND OBJECTIVE: Cryosurgery is a widely accepted modality for the treatment of capillary hemangiomas of the newborn. However, no studies clearly supporting its effectivity are available. PATIENTS AND METHODS: Out of 116 consecutive outpatients with 147 hemangiomas, 105 growing tumors in 91 patients were treated by cryosurgery. 13 further growing tumors were not treated because of lack of parental consent. Hemangiomas without growth within the last 2 weeks and with clinical signs of regression were not treated. After a follow-up of 1 year, the outcome of the treatment was classified as either regression (> 10% size reduction), no change (size alteration < 10%) or progression (> 10% size growth). The effectiveness of the treatment was assessed as clinical improvement of the hemangioma on an arbitrary scale per treatment session. RESULTS: Cryosurgery of growing hemangiomas efficiently initiated the regression phase (p < 0.05), in the most cases (68%) after a single treatment. Cryotherapy was most effective when employed in older children (p < 0.05) and for small hemangiomas (p < 0.05). Probably, this reflects associated spontaneous regression. CONCLUSIONS: Thus cryosurgery is a verifiably effective treatment modality for infantile capillary hemangiomas, shortening significantly their growth phase.
Cryosurgery↗
Use of the recursion formula of the Gompertz function for the quantitation of PCR-amplified templates.
One common drawback of the currently used procedures to quantitate the polymerase chain reaction (PCR) is that the statistical evaluation of the experimental data depends on many, not just trivial, model assumptions. In the present study we report on an improvement in this crucial step of the quantitative PCR. The experimental design underlying the introduced method is exactly the same as in the case of the so-called PCR. However, by applying growth curve analysis based on the recursion formula of the Gompertz function the kinetics of the accumulation of the amplicon are estimated conjointly from data spanning both the and phases of the reaction. We demonstrate the method by determining the relative number of templates (a 206 bp segment spanning the exon 3 of the X-chromosomal murine Hprt-gene) contained in known orders of dilutions of DNA isolated from the spleen of the C57BL/6J-mouse. [32P]-dATP incorporation was used in duplicate experiments to quantify the amplicons as a function of amplification cycles. Our results: i) indicate that the accumulation of the PCR product as a function of PCR cycles follows a sigmoidal pattern compatible with the Gompertz growth model (P<0.0000001); ii) directly support the thesis that the kinetical pattern of accumulation of amplicons of a given DNA fragment does not depend on the number of corresponding DNA templates provided to the reaction; iii) permit a simple direct evaluation of the parallelity in the course of the accumulation of amplicons from different template numbers as a function of amplification cycles, which is a silent preposition in the evaluation of the so-called PCR; iv) allow an easy quantitation of the relative number of provided templates.
Gene Amplification↗
Acne inversa (pyodermia fistulans sinifica) and smoking.
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Acne Vulgaris↗
Is the expression of multidrug resistance gene product a prognostic indicator for the clinical outcome of patients with renal cancer?
OBJECTIVE: To determine the significance of the expression of the multidrug resistance gene product (MDR-1) for the aggressiveness of renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 31 patients with clinically locally confined RCC treated with radical nephrectomy (mean age 64.1 years, range 41-78; mean follow-up 5.4 years, range 4.3-7.3). Their survival time and disease-free period were evaluated retrospectively. The expression of the MDR-1 gene product was determined immunohistochemically using the JSB-1 antibody in formalin-fixed paraffin-embedded tumour samples from these patients. The significance of this variable and tumour stage and malignancy grade was assessed for predicting the survival and disease-free period using Kaplan-Meier plots (log-rank test or Tarone's test) and the Cox multiple hazard regression analysis. RESULTS: In a univariate analysis, tumour stage (P < 0.002), malignancy grade (P < 0.007) and MDR-1 (P < 0.03) were significant prognostic variables for both survival and disease-free period. Lower MDR-1 expression was correlated with poorer prognosis. On multivariate analysis, MDR-1 and tumour stage were significant factors for predicting the disease-free period, whereas tumour stage and malignancy grade were the most relevant factors for survival time. Calculating prognostic indices based on the results of the Cox analysis, MDR-1 could replace malignancy grade, resulting in a better prediction of survival and disease-free period (P < 0.001 vs 0.0031, P < 0.001 vs 0.021, respectively). CONCLUSION: MDR-1, an established predictor for chemo-resistance, may also be a potent prognostic factor for outcome in patients with locally confined RCC. Moreover, MDR-1 expression seems to correlate with the differentiation of the RCC and thus its value as an objective measure of the degree of differentiation should be further explored.
Adult↗
Epidermal growth factor family and renal cell carcinoma: expression and prognostic impact.
OBJECTIVE: Expression and prognostic impact of some exponents of the epidermal growth factor (EGF) family in renal cell carcinoma (RCC) were examined. MATERIALS AND METHODS: EGF, transforming growth factor-alpha (TGF-alpha), EGF receptor (EGF-R), and c-erb B-2 were determined immunohistochemically in formalin-fixed paraffin-embedded tumor samples of 30 patients with locally confined RCCs. The prognostic significance of these growth factors and their receptors as well as of tumor stage and malignancy grade was examined with respect to survival and tumor recurrence by following up the fate of the patients after nephrectomy (mean follow-up time 5.2 years). RESULTS: The members of the EGF family and their receptors studied were expressed to a variable degree in all RCCs investigated. However, using log-rank tests in Kaplan-Meier plots only tumor stage (p < 0.0007) and malignancy grade (p < 0.007) but none of the growth factors or receptors studied (p > 0.05, respectively) exhibited prognostic significance with respect to both survival and disease-free period. On the contrary, there was a significant correlation between EGF and TGF-alpha (p < 0.001), EGF and EGF-R (p = 0.028), EGF-R and c-erb B-2 (p = 0.0009), and-inversely related-between TGF-alpha and tumor stage (p = 0.047) and between EGF-R and malignancy grade (p = 0.03). The coexpression of the factors studied also showed no prognostic relevance. CONCLUSION: The expression of these members of the EGF family seems not to bear evaluable prognostic information for clinical use in the case of RCC.
Adult↗
Prognostic relevance of the intrinsic growth deceleration of the first passage xenografts of human renal cell carcinomas.
BACKGROUND: Although successful xenotransplantation of human tumors in nude mice highly predicts prognosis, little is known regarding the biologic background of this correlation. In this study, the relationship between the macroscopic growth pattern of first-generation xenografts of human renal cell carcinomas in nude mice and prognosis was studied. METHODS: Macroscopic growth patterns of the first-generation xenografts of locally confined renal cell carcinomas were analyzed according to the best-fit Gompertz recursion formulas. RESULTS: The parameter "b" of the growth pattern, the measure of the intensity of growth deceleration as a function of tumor growth, strongly predicted prognosis after nephrectomy as a single factor; faster growth deceleration, i.e., lower b values, predicted better prognosis (mean follow-up, 5.2 years; P = 0.000008 for the disease free period and P = 0.000018 for overall survival). It is also the most significant single prognostic parameter among others (including staging and grading) according to a multivariate analysis. CONCLUSIONS: The parameter expressing the Gompertzian macroscopic growth deceleration of the first-generation xenografts of clinically locally confined renal cell carcinomas in nude mice explains the strong prognostic impact of xenotransplantation.
Animals↗
Use of the recursion formula of the Gompertz survival function to evaluate life-table data.
The recursion formula of the Gompertz function is an established method for the analysis of growth processes. In the present study the recursion formula of the Gompertz survival function 1n S(t + s) = a + b x ln S(t) is introduced for the analysis of survival data, where S(t) is the survival fraction at age 1, s is the constant age increment between two consecutive measurements of the survival fraction and a and b are parameters. With the help of this method--and provided stroboscopial measurements of rates of survival are available--the Gompertz survival function, instead of the corresponding mortality function, can be determined directly using linear regression analysis. The application of the present algorithm is demonstrated by analysing two sets of data taken from the literature (survival of Drosophila imagoes and of female centenarians) using linear regression analysis to fit survival or mortality rates to the corresponding models. In both cases the quality of fit was superior by using the algorithm presently introduced. Moreover, survival functions calculated from the fits to the mortality law only poorly predict the survival data. On the contrary, the results of the present method not only fit to the measurements, but, for both sets of data the mortality parameters calculated by the present method are essentially identical to those obtained by a corresponding application of a non-linear Marquardt-Levenberg algorithm to fit the same sets of data to the explicit form of the Gompertz survival function. Taking into consideration the advantages of using a linear fit (goodness-of-fit test and efficient statistical comparison of survival patterns) the method of the recursion formula of the Gompertz survival function is the most preferable method to fit survival data to the Gompertz function.
Aged↗
Age dependent selection against HPRT deficient T lymphocytes in the HPRT+/- heterozygous mouse.
The fraction of HPRT deficient T lymphocytes was measured in the HPRT +/- female mouse between birth and an age of about 2 years. The animals were the F1 offspring of the HPRT deficient strain 129MF1 and HPRT competent C57BL/6J-mice. T lymphocytes from spleen were cloned in vitro and HPRT deficient clones were detected by double-labeling with [3H]thymidine and [14C]hypoxanthine. During the first weeks of life the fraction of deficient lymphocytes sharply decreases from about 50% at birth to 10-30% at an age of 10 weeks. In adult animals the fraction of HPRT deficient T cells smoothly further decreases to values about 10% at 80-90 weeks. The equation gamma(t)=[0.547 x exp(-0.405 x t)] + [0.453 x exp(-0.0116 x t)] was found to be a good approximation of the time course of HPRT deficient cells in spleen; gamma(t) is the fraction of deficient cells per competent cell and t is the age of animals in weeks. It is postulated that the selection against HPRT deficient T lymphocytes is the consequence of the reduced proliferative capacity of HPRT deficient cells (=selection factor). The time course of the ratio of deficient cells can be described as a function of the proliferation rate of the HPRT competent T cells and this selection factor. The sharp initial decrease is explained by a high selection pressure against HPRT deficient cells in young animals when the proliferation rate of the expanding T cell population is high and when T cells proliferate in the bone marrow. In adult animals the selection pressure against HPRT deficient cells is reduced, since T cells arise in general in peripheral lymphatic organs, where the salvage pathway is of lesser importance compared to the de novo purine synthesis. Implications of the selection against HPRT deficient lymphocytes for the widely used HPRT mutation assay are discussed.
Aging↗
Significance of conventional and new prognostic factors for locally confined renal cell carcinoma.
BACKGROUND: The prognosis of patients with locally confined renal cell carcinoma is variable. To improve the prognostic knowledge and select patients at high risk, additional prognostic parameters are needed. METHODS: The significance with respect to survival and tumor recurrence of "classic" and "new" prognostic parameters has been examined by following 41 patients with locally confined renal cell carcinoma after nephrectomy (mean follow-up, 5.2 years). The significance of histologic grade, tumor stage, Ki-67 index, proliferating cell nuclear antigen index, 3H-thymidine labeling index, tumor ploidy status, and tumor growth after xenotransplantation into nude mice (GAX range) was tested using the Kaplan-Meier plots by the log rank test or Tarone's test and also by the Cox multiple hazard regression analysis. RESULTS: Tumor stage (P < 0.0025), histologic grade (P < 0.005), Ki-67 index (P < 0.006), and GAX range (P < 0.00004) were found to be significant prognostic parameters for survival and tumor recurrence using single-factor analysis. Applying the multivariate analysis, the combination of the "new" factors, GAX range and Ki-67 index, resulted in even a higher prognostic relevance than the combination of the "classic" prognostic factors, tumor stage and histologic grade. The calculated prognostic index based on the results of the Cox analysis, which, except for stage and grade, included the Ki-67 index, was shown to be highly correlated with survival (P = 0.00002) and tumor recurrence (P = 0.0004). Its prognostic validity was studied with the receiver operating characteristics procedure and was found to be considerably superior to that of the two conventional prognosticators. CONCLUSIONS: The additional determination of the Ki-67 labeling index increases the prognostic assessment of patients with locally confined renal cell carcinoma.
Animals↗
Effect of biological response modifiers on growth and cell proliferation of human tumor xenografts in nude mice.
The effect of biological response modifiers on macroscopic tumor growth and on tumor cell proliferation of a human renal cell carcinoma and a squamous cell carcinoma (hypopharynx) in nude mice has been studied. Tumor necrosis factor alpha (TNF-alpha) and interferon alpha (IFN-alpha) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) were applied either alone or in combination, and TNF-alpha was also combined with etoposide (ETP). TNF-alpha and IFN-alpha alone or in combination did not substantially affect the course of tumor growth, however, they did influence the pattern of tumor growth. There was also only a marginal effect on tumor cell proliferation. However, IFN-alpha protects the animals from tumor growth associated weight loss. ETP and ETP plus TNF-alpha leads to a deceleration of tumor growth, a decrease of the labeling index and to a significant decrease of the animal weight which indicates that the first two effects may be partly due to the toxicity of the treatment. GM-CSF modifies cell proliferation in a dose-dependent manner, i.e. stimulation at low doses and tendency to inhibition at higher doses. Although there is no substantial direct antineoplastic effect of the agents studied, the results make clear that indirect effects of therapeutic agents due to therapy induced cachexia should always be regarded. It is interesting that IFN-alpha has a protective effect against cachexia.
Animals↗
Comparative Gompertzian analysis of alterations of tumor growth patterns.
We have shown previously that different patterns of growth (including classical Gompertzian, exponential, and hyperexponential) can be described based on the Gompertzian difference equation, In G(t+s) = a+b In G(t) [G(t), tumor size at time t; s, constant time interval of a stroboscopic set of tumor size measurements], by the initial or intrinsic growth rate, a, and the exponential rate of growth deceleration, b (I. D. Bassukas and B. Maurer-Schultze, Growth Dev. Aging, 52: 113-122, 1988). Particularly, the possible effects of antineoplastic treatments on this latter factor have not been adequately appreciated to date. In the present study a new method of comparison of growth process is introduced, which consists of two steps. (a) The corresponding growth patterns are compared with each other on the basis of the Gompertzian difference equation using an analysis of variance algorithm. The result indicates whether or not there is an alteration of the growth pattern and, if there is one, whether it refers to alterations of the a and/or b values for the growth patterns. (b) The ultimate effect of any perturbation is assessed by using the limit (for t-->infinity) of the quotient of the tumor sizes after and before perturbation to characterize it as stimulation or inhibition. The present approach introduces a new quality of tumor growth perturbations; tumor growth may be altered although being neither inhibited nor stimulated, a phenomenon with biological significance still to be evaluated. The application of this method to the treatment with suramin of a human renal cell carcinoma xenograft in nude mice reveals a complex alteration of its growth pattern. Suramin simultaneously inhibits both the initial or intrinsic growth rate and the exponential rate of growth deceleration of this tumor. Consequently, this tumor starts with a lower growth rate in the presence of suramin; however, this rate also decelerates more slowly as a function of tumor growth, so that treated tumors, although initially inhibited, grow larger than controls.
Animals↗
Gompertzian re-evaluation of the growth patterns of transplantable mammary tumours in sialoadenectomized mice.
The method of the recursion formula of the Gompertz function (Bassukas & Maurer-Schultze 1988) has been applied to analyse tumour growth data taken from the literature; namely the growth perturbation of transplantable mammary tumours in sialoadenectomized mice with or without subsequent epidermal growth factor substitution (results on two mouse strains, C3H or SHN, have been reported; Inui, Tsubura & Morii 1989). The recursion formula of the Gompertz function fits growth curves to all seven sets of data well (P > 0.05 for lack of fit test). The growth pattern of the tumours in the unperturbed hosts is Gompertzian and does not change if tumours are transplanted in sialoadenectomized mice, although the starting specific growth rate decreases in C3H mice. However, if sialoadenectomy is carried out after tumour inoculation, a complex alteration of the tumour growth evolves: tumour growth does not simply decelerate but it also shifts from the conventional Gompertzian to an exponential or even 'hyperexponential' growth pattern, i.e. with an accelerating specific growth rate. Some theoretical mechanisms of this alteration, as well as the differences between the present Gompertzian analysis and a previously published Verhulstian analysis of part of the same data (Leith, Harrigan & Michelson 1991), are discussed. It is concluded that the quantitative analysis of tumour growth patterns by the method of the difference equation of the Gompertz function presently applied may substantially contribute to the improvement of the interpretation of perturbations of tumour growth--irrespective of their genesis. In contrast to the application of some a priori fixed growth function, e.g. the Verhulstian one, the present method can quantitatively interpret different growth patterns and their classification on the basis of linear regression analysis.
Animals↗
Evidence for a narrow range of growth patterns of malignant tumors and embryos of different species.
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Animals↗
Treatment of a human renal cell carcinoma in nude mice with recombinant human tumor necrosis factor alpha and etoposide.
The effect of treating a human renal cell adenocarcinoma xenografted into Balb/c-nu/nu (nude) mice with recombinant human tumor necrosis factor alpha (TNF alpha) and the cytostatic agent etoposide (ETP) as monotherapy or combination has been studied. Antitumor effects were evaluated by determining growth of the tumor implants by external caliper measurements and tumor cell proliferation by determining the labelling index (LI) after pulse labelling with 3H-thymidine. The toxicity of the treatment with TNF alpha and/or ETP was also studied by measuring the animal weight. Monotherapy with TNF alpha had no effect on tumor growth or proliferation. Treatment with ETP as a single agent, TNF alpha plus ETP applied concurrently and TNF alpha plus ETP two days later led to a slight inhibition of tumor growth and also to a slight decrease of the LI. In contrast to a monotherapy with TNF alpha, all therapeutic modalities containing ETP showed an increased toxic effect on the animals represented by a distinct weight loss. This suggests that the minute efficacy of the treatment observed could well be due solely to its toxicity. In contrast to two other studies, no additive or synergistic effect of the antineoplastic activity of TNF alpha and/or ETP was found. The intertumoral variation of human renal cell carcinomas could be one reason for the different results with this therapeutic regimen.
Animals↗
Structural relationship between epidermal lipid lamellae, lamellar bodies and desmosomes in human epidermis: an ultrastructural study.
The water permeability of the stratum corneum (SC) appears to be regulated primarily by the lamellar arrangement of lipid bilayers between the corneocytes. A significant body of evidence already exists, suggesting that the specific structural organization of these intercellular lipid lamellae is responsible for the very low water permeability of the intact skin and that these lipid-rich structures may also influence the process of desquamation in the SC. In this electron microscopic study the structure of the intercellular domains at different levels within the SC of normal skin from 18 healthy subjects has been evaluated with a special fixation protocol utilizing acrolein vapour as primary fixation, followed by a modified ruthenium tetroxide (RuO4)-post-fixation technique. This procedure permitted an insight into the process of post-secretory extracellular processing of the lamellar body (LB)-derived lipids into lamellar lipid bilayers. This transformation takes place in unique saccular invaginations of the intercellular domains, which indent the underlying stratum granulosum (SG) cells. In this specialized environment LB lipids are first processed into broad sheets before they become part of the typical lamellar lipid structure of the SC. Furthermore, in the process of lipid maturation distinct differences between inner and outer parts of the SC emerge, in particular an increase in both the number of the lamellae per intercellular space, and their order of arrangement. Moreover, distinct structural relationships between desmosomes (at the SG/SC interface and lower SC) and desmosomal remnants (at the stratum disjunctum) on the one hand, and lipid layers on the other, have been demonstrated, pointing to an important functional interaction of these components in normal human skin.
Adult↗
Cell proliferation in human tumours growing in nude mice: renal cell carcinomas, larynx and hypopharynx carcinomas.
Cell proliferation of 51 human renal cell carcinomas and 9 larynx and hypopharynx carcinomas has been studied in vitro and using xenotransplants. The proliferative activity ([3H]thymidine labelling index) increases during the first passages in nude mice and then remains almost constant throughout subsequent passages. A comparison of cell kinetic parameters of 8 human renal cell carcinomas, 1 hypopharynx and 2 larynx carcinomas, with data of xenografts and of human tumours in situ published up to now, shows that the cell kinetic parameters of human tumour xenografts presently studied range between those of human tumours in situ and those of autochthonous or transplantable mouse tumours. S-phase durations and potential doubling times are considerably shorter in xenotransplants than in human tumours in situ, whereas the cycle time is about the same. This means that the growth fraction increases considerably after xenotransplantation. This change of human tumour cell proliferation after transplantation into nude mice should be kept in mind if one wishes to draw conclusions from the nude mouse model on conditions in human beings, particularly with respect to therapeutic regimens, which are frequently tested in the nude mouse model.
Animals↗
Is erythema toxicum neonatorum a mild self-limited acute cutaneous graft-versus-host-reaction from maternal-to-fetal lymphocyte transfer?
Erythema toxicum neonatorum (ETN) is a common, self-limited neonate dermatosis affecting worldwide about 50% of newborns--mostly second and later deliveries--irrespective of sex and race. Its etiology still remains obscure: some reaction of the skin of the newborn in adapting to its new environment is the favorite hypothesis to date. A suggested viral or allergic nature could not be confirmed by adequate agent or antigen isolation respectively. In this paper a hypothesis is presented that ETN is a self-limited acute cutaneous graft-versus-host reaction (GVHR) caused in the transiently immunosuppressed newborn by maternal lymphocytes transferred shortly prior to or during delivery.
Erythema↗