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Biomedical subjects

A Wahl

Publications and source records attributed to A Wahl.

At least 55 records · Page 3Linked to original sources

The impact of psoriasis on psychosocial life domains. A review.

Living with a chronic disease, such as psoriasis, is likely to have psychological as well as social implications. Hence, knowledge about the impact of psoriasis on patients' life situation is important for designing and selecting suitable health care programmes for this group of patients. A review of studies published between 1983 and 1995 shows that there are some common factors as regards the psychological distress and social and functional limitations this group of patients has to deal with. However, it is difficult to compare the findings on the psychosocial impact of psoriasis owing to the differences in methods, study design and patient samples. This suggests that further research is needed. A holistic perspective that includes patients' quality of life may represent a fruitful approach.

Adaptation, Psychological↗

Numerical chromosome anomalies after fertilization of freeze-thawed mouse oocytes.

The chromosome complement of first cleavage stage mouse embryos was analyzed to investigate the effect of slow freezing-fast thawing cryopreservation on chromosome numbers by comparing these numbers with those found fresh after fertilization of control oocytes. Fewer frozen-thawed (34.1%) than control oocytes (75.0%) cleaved to the 2-cell stage after in vitro fertilization. The incidence of hyperploidy was significantly increased by freezing (4.5% vs. 0% in controls). Polyploidy was not significantly affected (17.0% for freeze-thaw embryos vs. 26.2% for controls).

Aneuploidy↗

Establishment in monolayer culture and characterization of four human melanoma cell lines.

Four new human melanoma cell lines were established in monolayer culture from xenograft lines originating from different patients. Several distinct characteristics of the source xenograft lines were retained in the cell lines, e.g., number of chromosomes, DNA-index, and cell ultrastructure. Cell volume was generally larger for the cell lines than for the corresponding xenograft lines, but the differences among the lines were similar in vitro and in vivo. The cell lines showed significant differences in growth pattern, i.e., cell motility and degree of intercellular contact. Cell cycle time (Tc) during exponential growth ranged from 15 to 21 h. The differences among the lines in Tc were mainly due to differences in the duration of S. Growth fraction was close to 100% and cell loss was negligible during exponential growth. Plating efficiency was 90-100% in the presence of feeder cells. The four cell lines represent a valuable supplement to the xenograft lines for future studies of the cell biology, pathophysiology, metastatic behavior, and treatment sensitivity of malignant melanoma.

Cell Cycle↗

Establishment and characterization of six human melanoma xenograft lines.

Six new human melanoma xenograft lines differing considerably in biological properties were established in athymic nude mice and characterized with respect to growth in vivo. Mean volume-doubling time ranged from 1.8 to 17.7 days, mean necrotic fraction from 7 to 39%, and mean fraction of cells in S from 11 to 31% at a tumor volume of 500 mm3. DNA-index and median chromosome number were in the ranges 1.15-1.76 and 46-80, respectively. The lines were all highly malignant by histopathological criteria, but showed significant differences with respect to cell type, cellular pleomorphism, nuclear atypia, nucleolar prominence, and mitotic activity. Several biological characteristics of the donor patients' melanomas were retained in the xenograft lines. All lines showed a human karyotype and the histological appearance was very similar to that of the source tumor material. The distribution of cells in the cell cycle was comparable to that reported for melanomas in man. The six melanoma xenograft lines constitute a tumor panel that shows great promise for future studies of the biology and treatment sensitivity of malignant melanoma.

Adult↗

Radiation sensitivity in vitro of cells isolated from human tumor surgical specimens.

The radiation sensitivity of cells isolated directly from human tumor surgical specimens was studied using the Courtenay soft agar colony assay. Aerobic cell survival curves covering 2-3 decades were achieved for eight melanomas, seven ovarian, six cervix, five breast, four bladder, and four squamous cell carcinomas of the head and neck and two seminomas. Cell survival following exposure to 2.0 Gy was measured also for several other tumors of these histological types. Experiments repeated with cells stored in liquid nitrogen showed that the survival assay gave highly reproducible results. The D0 (0.61-1.65 Gy) as well as the surviving fraction at 2.0 Gy (0.12-0.66) differed considerably among individual tumors of the same histological type. Neither of these parameters was therefore significantly different for the seven tumor categories. However, about one-third of the melanomas showed a higher surviving fraction at 2.0 Gy than the highest value measured for the other tumors. Two of three seminomas showed surviving fractions at 2.0 Gy in the absolute lower range, i.e., below 0.20. Altogether the data were consistent with the suggestion recently put forward that the clinical radiocurability of tumors may be correlated to the cell surviving fraction in vitro at 2.0 Gy. However, it was not possible on the basis of individual tumors to investigate whether the surviving fraction at 2.0 Gy was correlated to the clinical radiocurability, since adequate clinical data were not available for the parent tumors. It is suggested that melanomas may be especially suitable for prospective studies aimed at establishing whether such a correlation really does exist. If a significant correlation can be verified, then a very important conclusion may be drawn from our data: the radiocurability of human tumors may differ almost just as much among individual tumors of the same histological type as among individual tumors of different histology.

Cell Survival↗

Hepatocellular carcinoma and hepatitis B virus infection: molecular evidence for monoclonal origin and expansion of malignantly transformed hepatocytes.

The clonality of tumor cells was studied in a patient with metastasizing hepatocellular carcinoma (HCC). Using hepatitis B virus (HBV) DNA as a genetic marker, the pattern of integration of viral DNA into the tumor cell genome was determined by Southern blot analyses of DNAs extracted from different HCC lesions in the liver and both lungs. All tumor tissues examined were found to have viral DNA integrated into the same site(s) of the cellular genome. This finding provides direct molecular evidence for a monoclonal origin and expansion of malignantly transformed hepatocytes during tumor growth and metastasis. This characteristic is similar to other human cancers associated with viral infections, such as adult T-cell leukemia, Burkitt's lymphoma, or cervical cancer, and is important for our understanding of viral oncogenesis in man.

Aged↗

Radiation response of human melanoma multicellular spheroids measured as single cell survival, growth delay, and spheroid cure: comparisons with the parent tumor xenograft.

The radiation response of multicellular spheroids, initiated from a human melanoma xenograft (E.E.) propagated in athymic mice, was studied using cell survival, growth delay, and spheroid cure as endpoints. The relationship between these endpoints was analyzed, and the radiation response of the spheroids was compared with the parent xenograft. At irradiation, the spheroids were 100 +/- 5 micron in diameter and did not contain radiobiologically hypoxic cells. Growth delay of the spheroids mainly depended on the fraction of surviving cells as measured in soft agar, that is, there was a good correlation between these two endpoints. Moreover, Do-values calculated from spheroid cure curves were similar to those of the cell survival curves measured in soft agar. However, the number of stem cells per spheroid, calculated from SCD50-values (the doses required to cure 50% of the spheroids), was at least a factor of seven lower than the clonogenicity of cells from disaggregated spheroids would indicate. The cellular radiosensitivity of the spheroids was similar to the parent xenograft. An intercellular contact effect was not found for the spheroids, in agreement with observations from studies of xenografted tumors. Moreover, specific growth delays, as well as Do-values calculated from cure curves were similar for spheroids and tumors when the data for the latter were corrected for the presence of hypoxic cells. The high degree of conformity in the results indicates that multicellular spheroids and xenografted tumors may complement one another in studies of human tumor radiobiology.

Animals↗

Growth characteristics of human melanoma multicellular spheroids in liquid-overlay culture: comparisons with the parent tumour xenografts.

The growth characteristics of multicellular spheroids, derived from human melanoma xenografts and cultivated in liquid-overlay culture, were studied and compared with those of the parent tumours. Six of the seven melanomas investigated formed spheroids, which grew exponentially up to a volume of 1-2 X 10(7) microns 3 (a diameter of 270-340 microns) before the growth rate tapered off. The morphology of the spheroids varied considerably among the melanomas; some spheroids grew as densely packed, spherical structures of cells whereas others were loosely packed and showed an irregular shape. Central necrosis developed when the spheroids attained a diameter of 150-200 microns. The histological and cytological appearance of the spheroids was remarkably similar to that of the parent xenograft in five of the six cases. The sixth melanoma contained two subpopulations with distinctly different DNA content, one of which was predominant in the spheroids, the other in the tumours. This gave rise to clear histological and cytological differences. The volume-doubling time of the spheroids during the exponential growth phase ranged from 1.7 +/- 0.2 to 2.7 +/- 0.4 days and the fraction of cells in S from 13 +/- 1 to 28 +/- 2%. The volume-doubling time decreased with increasing fraction of cells in S, indicating that the differences in growth rate were due mainly to differences in the growth fraction or to differences in the duration of G1. The spheroid volume-doubling times did not correlate with those of the parent xenografts (Td = 4.2-22.5 days at V = 200 mm3), possibly because the cell loss factors of the xenografts were large and varied among the melanomas. The fractions of cells in G1/G0, S and G2 + M in the spheroids and the xenografts did not correlate either, but were found to be within the same narrow ranges in the spheroids and the xenografts--i.e. 50-80% (G1/G0), 10-30% (S) and 10-20% (G2 + M).

Animals↗

Radiation response of multicellular spheroids initiated from five human melanoma xenograft lines. Relationship to the radioresponsiveness in vivo.

Multicellular spheroids, initiated from five human melanoma xenograft lines (E.E., E.F., G.E., M.F., V.N.) and grown in liquid-overlay culture, were characterised with regard to radiation response. The principal aim of the work was to search for possible correlations with the radioresponsiveness in vivo of the parent xenografts. The spheroids were 100 +/- 5 microns in diameter at irradiation and did not contain radiobiologically hypoxic cells. Single-cell survival measured in soft agar, specific growth delay and spheroid cure were used as end-points. The cellular radiosensitivity was the same whether a melanoma was grown as spheroids or as xenografts. An intercellular contact effect was found for spheroids of the G.E. melanoma but not for spheroids of the E.E., E.F., M.F. and V.N. melanomas, in agreement with previous observations from studies of the corresponding xenografts in vivo. A positive correlation was found between the radiation response of the spheroids, measured as cell survival after 6 Gy or as specific growth delay after 6 Gy, and the radiation response of the parent tumours, measured as specific growth delay after 15 Gy. There was no correlation between the SCD50 (the dose required to cure 50% of the spheroids) and the radioresponsiveness in vivo. It is concluded that differences in radioresponsiveness in vivo among tumours may be identified from studies of the corresponding multicellular spheroids grown in liquid-overlay culture.

Animals↗

Photodynamic effects and hyperthermia in vitro.

Cells from the established human line NHIK 3025 were labelled with hematoporphyrin derivative in vitro. Subsequently, the cells were treated with light and hyperthermia. The cells could be irradiated either before, during or after the incubation at a hyperthermic temperature. It was shown that hyperthermia given shortly after the light exposure gave a synergistic killing effect. In spite of some loss of porphyrins from the cells, the light sensitivity increased 20 min after a light irradiation. At later times, the cells apparently repaired some of the photodynamic damage at 37 degrees C. At higher temperatures, the repair was inhibited.

Carcinoma in Situ↗

Survival curves after X-ray and heat treatments for melanoma cells derived directly from surgical specimens of tumours in man.

X-ray and heat survival curves were established for melanoma cells derived directly from surgical specimens of tumours in man by using the Courtenay soft agar colony assay. The plating efficiency for 11 of the 14 melanomas studied was sufficiently high (PE = 0.3-58%) to measure cell survival over at least two decades. Experiments repeated with cells stored in liquid nitrogen showed that the survival assay gave highly reproducible results. The melanomas exhibited individual and characteristic survival curves whether exposed to radiation or heat (43.5 degrees C). The Do-values were in the ranges 0.63-1.66 Gy (X-rays) and 33-58 min (heat). The survival curves were similar to those reported previously for human melanoma xenografts. The radiation sensitivity of the cells was not correlated to the heat sensitivity. Since the melanomas appeared to be very heterogeneous in radiation response in vitro as melanomas are known to be clinically, it is suggested that melanomas may be suitable for prospective studies aimed at establishing whether clinical radioresponsiveness somehow is related to in vitro survival curve parameters.

Adult↗

Heat response of human melanoma multicellular spheroids: comparisons with single cells and xenografted tumors.

Multicellular spheroids were grown from cells derived directly from a human melanoma xenograft propagated in athymic mice. The histological appearance of the spheroids was similar to that of the parent xenograft. The spheroids were heated in culture medium (42.5-44.5 degrees C); growth delay and single cell survival measured in soft agar were used as end points. There was a good correlation between the results obtained with these two end points, indicating that growth delay depended mainly on cell survival. Large spheroids (200 +/- 12 microns in diameter) were found to be more heat sensitive than small ones (100 +/- 5 microns in diameter), probably because the physiological conditions in large spheroids were more favorable for cell inactivation. The cells were more resistant when heated as spheroids than as single cells. This effect was not a secondary effect of differences in cell-cycle distribution. Spheroids were also found to be more heat resistant than xenografted tumors. In the tumors, heat treatment caused vascular damage which resulted in delayed cell death due to hypoxia and/or nutrient deficiency. It is concluded that spheroids seem well suited for studies of primary heat-induced cytotoxic effects. However, they appear not to mirror the complex heat response of tumors since that response also includes secondary effects, related to heat-induced reduced perfusion.

Agar↗

Radiation and heat sensitivity of cells from two slowly growing human melanoma xenografts.

The radiation and heat sensitivity of cells from two melanin-rich, slowly growing human melanoma xenografts (B.E. and R.A.) were studied. The volume-doubling times of the xenografts in the volume range 200-500 mm3 were found to be 22.5 47.5 days (B.E.) and 25.3-39.2 days (R.A.). The cells were suspended in culture medium during irradiation or heating, and the colony forming ability of the cells was assayed in soft agar. The X-ray survival curve parameters were found to be: Do = 1.09 +/- 0.14 Gy, Dq = 1.99 +/- 0.58 Gy (B.E.); Do = 1.23 +/- 0.08 Gy, Dq = 2.03 +/- 0.35 Gy (R.A.). The Do-values of the heat survival curves were found to be 119.0 +/- 26.6 min (42.5 degrees C), 20.4 +/- 3.9 min (43.5 degrees C) and 9.6 +/- 1.6 min (44.5 degrees C) for the B.E. melanoma and 112.9 +/- 13.3 min (42.5 degrees C), 17.9 +/- 2.0 min (43.5 degrees C) and 7.7 +/- 0.5 min (44.5 degrees C) for the R.A. melanoma. Both the radiation and the heat sensitivities of the cells are within the range of sensitivities reported for rapidly growing melanoma xenografts, suggesting that the intrinsic radiation and heat sensitivity of tumour cells are not strongly related to the rate of tumour growth prior to treatment.

Animals↗

Effects of haematoporphyrin derivative and light in combination with hyperthermia on cells in culture.

Interactions between the photodynamic effect of haematoporphyrin derivative and hyperthermia are reported. Cells labelled with haematoporphyrin derivative and irradiated with red light were sensitized by heat, particularly when the cells were heated after the exposure to light. It is shown that there is a synergistic interaction between the photodynamic effect and hyperthermia (42.5 and 45 degrees C). Hyperthermia-induced inhibition of the repair of photodynamic damage is suggested as a mechanism for the interaction. The possibility that these findings may be advantageous to cancer therapy is discussed.

Antineoplastic Agents↗

[Serological diagnosis of viral hepatitis (author's transl)].

Properties of the infective agent, pathogenesis, epidemiology and host defenses of hepatitis-virus A and B are described. The usual serological tests for diagnosis of viral hepatitis are outlined and illustrated by six typical cases of different etiology and course.

Carrier State↗