PubMed Health⌕ Search

Biomedical subjects

I D Bassukas

Publications and source records attributed to I D Bassukas.

At least 37 records · Page 2Linked to original sources

In situ [3H]thymidine labelling of human hair papilla: an in vitro autoradiographic study.

The labelling index (LI) and the location of labelled cells in the papilla of human anagen scalp hair have been studied after in vitro [3H]thymidine (3H-TdR) pulse labelling. Forty-three anagen stage VI papillae from 2 individuals (both females, 25 and 55 years) obtained by micropreparation from deep scalp biopsies were analysed. Labelled cells were found only paraaxially in the basal third of the papilla, i.e. below Auber's line. The 3H-TdR-LI of the papilla cells (0.13 and 0.16%) is about 200-times lower than that of the hair matrix cells below the line of Auber (25.5 and 29.5%). The biological significance of this low proliferation rate in the anagen stage VI hair papilla of healthy human should be defined.

Adult↗

Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopics.

A characteristic feature of non-eczematous atopic dry skin (DS) appears to be an impaired water permeability barrier (WPB) function. The WPB is constituted by intercellular lipid lamellae, located between the horny cells of the stratum corneum (SC), which are provided by exocytosis of lamellar bodies (LB). The aim of this study was to elucidate whether alterations in the dynamics of LB-extrusion could be responsible for this WPB disturbance. In an ultrastructural morphometric comparison the relative volume of LB in the two uppermost subcorneal layers in DS of atopics (n = 9) and healthy skin of controls (n = 7) was determined. The LBs were differentiated into extracytoplasmic LB, i.e. with the cell membrane already fused, and intracytoplasmic LB, i.e. entirely located within the cell. The total volume in the two cell layers of the stratum granulosum did not differ between atopics and controls. However, separate evaluation of the two LB-compartments revealed statistically significant differences between atopics and healthy controls. In the second uppermost cell layer of the stratum granulosum only 13% of the total LB volume of this layer had already fused with the cell membrane in the atopics as opposed to 42% in the controls. On the other hand more LB remained undelivered within the cells of the uppermost SG cell layer of the atopics (26% in atopics versus 8% in controls, P < 0.01). These findings suggest that a pathological extruding mechanism of LB in DS may be at least partly responsible for the recently detected biochemical alterations of epidermal lipids, and for the deficient WPB.

Adult↗

Growth and cell kinetics of human hair papilla cells in vitro. An autoradiographic and flow cytometric study.

Hair papilla, a distinct specialized dermal compartment, plays a fundamental role in the biology of hair growth. Recently some attention has been focused on hair papilla cells (HPC) as possible targets for drugs influencing the hair growth. Isolation and cultivation of the HPC facilitates screening for such drugs. In the present work, growth and cell kinetics of human occipital scalp follicle HPC have been studied in vitro. HPC grow according to a Gompertz function, i.e. with considerable growth delay long before becoming confluent cultures, due probably to elongation of the potential doubling time (Tpot) and to a parallel increasing cell loss rate. The [3H]dT labelling index of the HPC strongly depends on the age of the subculture; the cycle time being about 4 days. A potential doubling time of about 93 h, indicative of growth fraction (GF) = 1, and a duration of S phase and G2 + M phase of about 8 h each were found by the combined application of continuous labelling with [3H]dT and DNA flow cytometry.

Adult↗

Clinically relevant differences between amelanotic malignant melanoma and granuloma pyogenicum.

Macroscopic discrimination between amelanotic malignant melanoma (aMM) and the so-called granuloma pyogenicum (GP) is often uncertain since reliable criteria for a clear differentiation of either growth are lacking. In a search of such criteria we analysed the data of 57 consecutive in-patients with cutaneous aMM and of 83 with GP presenting at our Department during the years 1970-1988. The following items were compared with each other: duration from growth onset to definite diagnosis, site of growth, age and sex of the patients. Significant differences (p less than 0.01) between either growth were found for all items evaluated. Our results substantiate the hitherto gained impression of a remarkably shorter median history of GP as compared to aMM (5 vs. 26 weeks). Furthermore, aMM prevailed in elder (age greater than 50 years) particularly female (70%) patients, whereas GP developed about equally in both sexes and at all ages. Site distribution was also found to differ for either growth (GP predominantly in the head and neck region, rarely on lower limbs; aMM in all areas, rarely on the trunk). These data yield additional measures for clinical distinction between aMM and GP.

Adolescent↗

Cell kinetic studies of endothelial cells in the adenocarcinoma EO 771 and the effect of cyclophosphamide.

Cell kinetic studies of endothelial cells in the adenocarcinoma EO 771 growing in C57bl/6j mice and after transplantation into Balb/c-nu/nu mice, as well as of the effect of cyclophosphamide treatment have been carried out. The 3H-thymidine labelling index of endothelial cells decreases from about 8% 3-6 days after tumour inoculation to about 3% at 18 days. This decrease parallels that of the labelling index of tumour cells, i.e. there is a positive correlation between the labelling index of endothelial cells and that of tumour cells. The labelling index of endothelial cells in the tumour periphery is two to three times as high as that in the tumour centre reflecting corresponding differences in the rate of proliferation. There is no difference in the proliferation of endothelial cells whether the tumour grows in C57bl/6j or in Balb/c-nu/nu mice. After treatment with cyclophosphamide the labelling index of endothelial cells decreases within 2 days to 1-2% and remains that low despite regrowth of the tumour with increased tumour cell proliferation, indicating that tumour relapse does not depend on tumour angiogenesis.

Adenocarcinoma↗

Growth and proliferation of a transplantable mouse tumor and of human tumors growing in nude mice.

Growth and proliferation were studied of a transplantable mouse tumor, the adenocarcinoma EO 771 (Adca EO 771) growing in C 57 and in nude mice on the one hand, and of human tumors (renal cell and hypopharynx carcinoma) growing in nude mice on the other. There is almost no difference in tumor growth, histology and proliferation whether the Adca EO 771 grows in C 57 or in nude mice. However, there are great differences in this respect between the transplantable mouse tumor and human tumors. Growth of the Adca EO 771 and C 57 and in nude mice occurs according to the Gompertz function, whereas growth of human tumors in nude mice differs, some tumors grow exponentially and some according to the Gompertz function. The proportion of necrotic tissue strongly increases with increasing tumor size in the case of the Adca EO 771, while it is about constant in human tumors regardless of the tumor size. The tumor cell density of the Adca EO 771 increases considerably with increasing tumor size, however, it remains about constant in human tumors. Concerning tumor cell proliferation an S phase duration was found that is rather similar for the cells of the transplantable mouse tumor as well as of the human tumors suggesting that DNA synthesis might be regulated by the host organism. A quantitative study of the growth of the metastases of the Adca EO 771 exhibited an allometric correlation between the growth of the metastases and that of the primary tumor. This leads to the consequence that metastases might originate later than estimated until now assuming exponential growth of metastases. Treatment of the Adca EO 771 with cyclophosphamide results in the death of almost all tumor cells; however the tumor repopulates. The toxic effect of cyclophosphamide on the mouse organism strongly depends on the size of the tumor at the time of treatment.

Adenocarcinoma↗

Effects of plucking on the anatomy of the anagen hair bulb. A light microscopic study.

The effects of mechanical plucking on the anatomy of human anagen hair bulbs were studied histologically in biopsy specimens taken from scalp areas of ten volunteers immediately after plucking. Anagen hair bulbs were shown to tear off not arbitrarily but in reproducible patterns which include, apart from the "typical" break conically surrounding the dermal papilla, three additional break forms: (1) rupture of the hair around the upper third of the papilla resulting in so-called dysplastic anagen hairs of the trichogram, (2) rupture of the hair well above the dermal papilla resulting in "broken" anagen hairs, (3) total removal of the proximal follicle epithelium with removal of the dermal papilla resulting in so-called papilla hairs of the trichogram. Plucking also gives rise to alterations of the mesenchymal sheath of the hair follicle mainly leading to hemorrhages and a distinct edema entailing an increase in the volume of both the dermal papilla and the underlying "papilla cushion" of Pinkus. The different break types can be due to inappropriate plucking techniques or may depend on different subphases of the anagen stage.

Adolescent↗

An in vivo study on the synchronizing effect of hydroxyurea.

The effect of hydroxyurea (HU; 0.5 mg/g body wt) on L 1210 ascites tumor cells has been studied using various cell kinetic methods. In contrast to the general assumption that HU blocks cells at the G1/S boundary [J. Brachet (1985) Molecular Cytology, Vol. I, p. 266, Academic Press, New York], the present results show that the cells are not held at G1/S but enter S at about the normal rate and are accumulated in early S phase due to a dose-dependent inhibiting effect of HU on DNA synthesis. Partial synchronization of the cells demonstrated by a distinct mitotic peak 10 h after HU application is not due to a G1/S block of the cells and their subsequent synchronous passage through the cycle after release from the block but is due to rather complex mechanisms of action of HU: a differential cytocidal effect and an effect on the passage of the cells through the cycle, both depending on the position of the cells throughout the cycle. HU kills S-phase cells, mainly cells in early S phase; i.e., a great portion of the cells "accumulated" in early S phase is killed by the drug, while G1-phase cells are almost not affected by the lethal effect of HU. These G1-phase cells pass through the cycle more rapidly after cessation of the HU effect. The same is true for the surviving cells accumulated in early S phase, while part of the cells in the remaining S phase are delayed in their passage through the cycle. This causes partial synchronization, since a great portion of all cells that survive HU treatment reach mitosis at the same time.

Animals↗

The recursion formula of the Gompertz function: a simple method for the estimation and comparison of tumor growth curves.

A method for analysing tumor growth curves is presented based on regression analysis of the linear relationship between the logarithm of the tumor size at a certain time and of that at a constant time interval earlier. By measuring the tumor size at constant time intervals the Gompertzian growth curve can be transformed into a straight line. This permits both the calculation of best fit Gompertzian curves and the comparison of different growth curves simply based on linear regression analysis. Since this new method includes exponential growth as a special case, it enables a quantitative discrimination between exponential and Gompertzian growth. Furthermore, this method permits the calculation of best fit Gompertz functions based upon individual measurements of tumor collectives without a common time scale (i.e., spontaneous tumors). As an example, it is demonstrated that the growth curves of the transplantable mouse adenocarcinoma EO 771 do not depend on the number of tumor cells inoculated.

Adenocarcinoma↗

Mechanism of growth retardation of the adenocarcinoma EO 771.

Growth retardation of tumors has been predominantly described by an increase of the "cell loss factor" phi. However, this cell loss factor alone merely reflects the growth deceleration without giving information on the mechanism that causes growth retardation. In the present study a quantitative analysis of the mechanism causing growth retardation of the adenocarcinoma EO 771 has been carried out by determining separately the components of the cell loss factor phi, namely the cell production rate and the cell loss rate of the tumor cell population. For this purpose the alteration of the histology of the tumor (proportion of necrotic tumor tissue, tumor cell density) and the proliferative capacity of the tumor cell population as a function of the tumor size was studied by applying morphometric and cell kinetic methods. The results show that growth deceleration is due to a decrease of the cell production rate kappa p and a simultaneous increase of the cell loss rate kappa l. Both processes contribute to about the same extent to the growth deceleration of the tumor cell population. In early tumor growth deceleration is mainly due to a prolongation of the cycle time of the tumor cells, in later phases of tumor growth to an increasing probability of the tumor cells to decycle leading to a decrease of the growth fraction GF and an increase of the cell loss rate kappa l.

Adenocarcinoma↗

A modification of the grain count halving method for detailed analysis of cell kinetic parameters.

A modification of the conventional grain count halving (GCH) method is presented. By determining the decrease of the mean grain number of all interphase cells in addition to that of all labelled interphase cells on the same autoradiographs, the potential doubling time Tpot (or the cell production rate kp) can be obtained in one and the same experiment. Thus the modified GCH method provides not only the cycle time of the cell population studied but also the growth fraction and, with additional cytofluorometric measurements, the duration of all cycle phases. By evaluating the cell production rate and the growth fraction this method leads to more reliable cell kinetic data of experimental tumours and human tumours growing in nude mice. In contrast to other cell kinetic methods, the modified GCH method can also be applied in special cases to human tumours in vivo, since only few points of measurement are needed. A comparison of the cell kinetic results obtained by the modified GCH method with those derived from the fraction of labelled mitoses method, both applied to allotransplants of the adenocarcinoma EO 771 in nude mice, shows good agreement.

Adenocarcinoma↗

Growth of metastases of the mouse adenocarcinoma EO 771: an allometric relationship between growth of the primary tumors and their metastases.

Growth and cell kinetic parameters have been studied of paraaortal lumbar lymph node metastases of the mouse adenocarcinoma EO 771 growing intramuscularly in the thigh. An allometric relationship was found between the growth of the metastasis and that of the primary tumor, i.e. a linear relationship exists between the logarithm of the size of the metastasis and that of the primary tumor which permits the estimation of the growth rate of the metastasis based on the growth curve of the primary tumor. However, growth of metastases differs quantitatively from that of the primary tumor: the specific growth rate (growth rate per unit size) of the metastasis (1) is greater than that of the simultaneously growing primary tumor but (2) is smaller than that of the primary tumor of the same size as the metastasis. The allometric growth relationship further suggests that metastases originate later than is generally predicted presuming exponential growth of metastasis.

Adenocarcinoma↗

The effect of tumor necrosis factor alpha on a human renal cell carcinoma xenotransplanted into nude mice: comparison of intravenous and intraperitoneal injection.

The effect of recombinant human tumor necrosis factor alpha (TNF-alpha) on tumor growth and tumor cell proliferation of a human renal cell carcinoma transplanted into nude mice as well as on the body weight of the tumor-bearing animals has been studied. Due to differences of the effect of TNF-alpha after intravenous and intraperitoneal injection reported in the literature the influence of the two routes of application was presently studied. There was no effect on tumor growth with either route of application. Only the mode of growth showed a tendency to an increased rate of growth at the beginning of the treatment and a following increased growth deceleration. A slight change of the 3H-thymidine labeling index and the mitotic index was observed only after intraperitoneal injection of TNF-alpha indicative of a more cytostatic than cytotoxic effect of the drug. This is supported by the lack of an increase of necrotic cells. Although a rather high dose of TNF-alpha was applied, no effect on the body weight of the animals, i.e. no toxic effect of the treatment, has been found.

Animals↗

The growth curve of the first passage xenografts of human tumors in nude mice predicts their transplantation behaviour.

The patterns of macroscopic growth of 20 first generation human tumor xenografts (16 renal cell carcinomas and 4 squamous cell carcinomas of the head and neck region) were studied with the recursion formula of the Gompertz function. This method enables the characterization of each tumor growth pattern by two parameters: (i) parameter a, which correlates with the starting growth rate of the tumor and (ii) parameter b, which is a measure of the intensity of growth deceleration as a function of tumor growth. A statistically significant prediction of the establishment of a xeno-transplantation line after serial subpassaging (in 9/20 tumors) according to the characteristics of first passage growth curves (p<0. 01) is reported. Especially parameter b, the value of the growth deceleration, highly correlates with serial growth: tumors showing less growth deceleration (higher b-values) during first passage more frequently develop into transplantation lines. On the contrary line development could not be predicted on the basis of the a-values of the first passage growth curves alone (p=0.137). This observation adds to the accumulating evidence, that the process of tumor growth deceleration is a pivotal parameter of tumor biology. Moreover, the present evaluation substantially reduces the time needed to assay serial growth of tumor xenografts for prognostic purposes making this assay potentially more attractive for clinical use.

Adenocarcinoma↗

Nobody needs "relative tumour sizes" to compare tumour growth curves.

Tumour growth curve experiments play an important role in experimental oncology and established methods exist for their unbiased interpretation. However, many authors till introduce systemic biases to their data by using the so-called "relative tumour size" transformation, inspite of wide awarance about the limitations of this latter method. With this communication and by using a fictive exaggeration of the problems connected with the application of this transformation we would like to appeal to both authors and reviewers likewise to ban this potential source of misinterpretation from the oncological literature.

Animals↗

Relationship between preimplantation host weight and growth of the mouse adenocarcinoma EO 771.

Growth curves of 26 EO 771 adenocarcinomas transplanted under identical conditions into 26 syngeneic C57bl/6 male mice of the same age but with different body weight were analyzed using the method of the recursion formula of the Gompertz function. The results of this analysis were then related to the body weight of the animals at the time of tumor implantation. Although all tumors grew according to the Gompertz mode of growth, the growth curves differed from each other. Moreover, there is a statistically significant correlation between the parameters of the individual growth curves and the corresponding animal weight at the time of tumor implantation (p less than 0.025). In animals with higher body weight the tumors grew with a higher initial growth rate and subsequently with a faster growth deceleration compared to animals with lower body weight. The physiological basis for this relationship is unknown but the question arises whether this relationship also has some meaning for human malignancies.

Adenocarcinoma↗

Relationship between tumor growth and cachexia during progressive malignant disease: a new measure of the extent of cachexia, the cachexia index.

The relationship between the dynamics of tumor growth and the development of cachexia in C57b1/6j mice bearing the syngeneic transplantable adenocarcinoma EO 771 has been studied. The tumors grow independently of the inoculum size according to the Gompertzian mode of growth, with a maximum growth rate at a tumor size of about 3 g. As a dynamic measure of the degree of cachexia, the cachexia index "K", i.e. the quotient of the alteration of the carcass weight of the animal divided by the alteration of the tumor weight during the same time interval, is introduced. K is superior to a simple estimation of the alteration of the carcass animal weight because it also considers local weight-reducing effects of the infiltrating tumor growth. With respect to cachexia, three phases of tumor growth can be distinguished; cachexia develops mainly during the 2nd phase, i.e. for tumor sizes between 1.0 to 3.5 g which strongly correlates with the maximum growth rate of the tumor.

Adenocarcinoma↗