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F Kallinowski

Publications and source records attributed to F Kallinowski.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effects of hydralazine-induced vasodilation on the energy metabolism of murine tumors studied by in vivo 31P-nuclear magnetic resonance spectroscopy.

The effects of hydralazine on tumor energy metabolism and on some cardiovascular parameters were measured. Tumor energy metabolism was studied in C3Hf/Sed mice with isotransplants of a spontaneous murine fibrosarcoma (FSaII, congruent to 100 mm3 in volume) and 31P-NMR. Cardiovascular parameters were measured in anesthetized C3Hf/Sed mice via intracarotid catheter. Hydralazine doses of 0.25 mg/kg given ip caused an increase of the phosphocreatine to inorganic phosphate ratio (PCr: Pi) in 5 of 6 animals. These doses had minimal effects on mean arterial blood pressure, though there may have been an increased cardiac output due to a decreased afterload. Hydralazine doses greater than or equal to 2.0 mg/kg given ip were associated with a decrease in PCr, nucleotide triphosphate, and pH, and an increase in Pi (P less than .01 for control vs. 10 mg hydralazine/kg). This substantial decrease in high-energy phosphates was associated with a pronounced decrement in mean arterial blood pressure. These findings provide a rational basis for the study in experimental systems of hydralazine-induced enhancement of cell killing by hyperthermia and by agents toxic to hypoxic cells. Further, these results can be taken as a sign that hydralazine should be used with care in patients undergoing radiation treatment.

Animals↗
PubMed1988

Action of the antileukemic and anti-HTLV-III (anti-HIV) agent avarol on the levels of superoxide dismutases and glutathione peroxidase activities in L5178y mouse lymphoma cells.

The antileukemic and anti-HTLV-III (anti-HIV) agent avarol, a sesquiterpenoid hydroquinone, was determined to be converted into its corresponding quinone derivative avarone via the semiquinone free radical. Its g-value was 2.0047; after hyperfine splitting the energy levels revealed 16 isotropic Hfs. The redox reaction products were identified at the pH values 4.0, 7.0 and 12.0 and the overall reaction pathways were formulated. In vivo experiments with L5178y mouse lymphoma cells in the ascites of mice revealed that the cytostatic potencies of avarol and avarone cannot be augmented by lowering the pH value. Incubation studies with L5178y cells in vitro showed that the intracellular levels of superoxide dismutases (SODases) and of glutathione (GSH) peroxidase activities significantly change after avarol administration. While both the Mn-SODase and the Cu/Zn-SODase activities dropped significantly, the GSH peroxidase activity increased inversely. From these experiments we assume that the anti-tumour and the antiviral effects of avarol/avarone may be due to an increase, induced by the drug, of the intracellular concentrations of superoxide radicals.

Animals↗
PubMed1988

pH distributions in spontaneous and isotransplanted rat tumours.

Spontaneous mammary tumours of the rat with various degrees of malignancy exhibit similar tissue pH distributions. The mean pH (+/- s.d.) of dysplasia is 7.05 +/- 0.20. In benign tumours the mean pH is 6.95 +/- 0.19 and in malignant tumours it is 6.94 +/- 0.19. In contrast, tumours with the same degree of malignancy but different histologies show different pH distributions. Benign tumours with a higher percentage of fibrous tissue exhibit less acidic pH values than those with larger portions of epithelial cells (delta pH = 0.38 pH units). The pH distribution in the benign tumours is independent of the tumour wet weight up to stages of very advanced growth. In the malignant tumours, a trend towards more acidic pH values is observed as the tumour mass enlarges. However, in tissue areas within a malignant tumour with gross, long-established necrosis the pH distribution is shifted towards more alkaline pH values. The pH distributions in spontaneous rat tumours are not significantly different from those obtained in isotransplanted Yoshida sarcomas (6.87 +/- 0.21). In the Yoshida sarcomas, mean pH values do not correlate with tumour size. However, a pH gradient from the rim to the centre of the tumours is found which coincides with the development of small, disseminated necroses in the tumour centre. It is concluded that pathology-related variations of tumour pH may be more important than the mode of tumour origin or the degree of malignancy.

Animals↗
PubMed1987

Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats.

Human breast cancer xenografts in T-cell-deficient rnu/rnu rats permit the detailed and systematic study of blood flow, oxygen supply, and characterization of the cellular microenvironment of human tumors in vivo. Using an epigastric pouching technique, it is possible to obtain a tissue-isolated preparation which makes direct studies of blood flow and oxygen supply in human tumors feasible. So far, medullary and squamous cell carcinomas of the breast from patients have been investigated under well-defined systemic conditions. At comparable tumor sizes, the average blood flow rate through human breast cancer xenografts is higher in medullary than in squamous cell carcinomas (0.17 versus 0.10 ml X g-1 X min-1). Blood flow per unit tumor mass significantly decreases with increasing wet weight. No significant differences are obvious when comparing the flow values of pre- and postmenopausal tumors or of cancer tissues with different hormone receptor capacities. On the average, the oxygen consumption rates of human breast cancer xenografts are 10.4 in medullary and 7.7 microliter O2 X g-1 X min-1 in squamous cell carcinomas. With increasing tumor mass, the O2 consumption rate per unit weight significantly decreases. This decrease parallels the respective decline of tumor blood flow, implying that the O2 consumption rate of the cancer cells in vivo is mostly limited by the nutritive blood flow, i.e., by the O2 availability to the tumors. Due to a restricted blood supply, the O2 utilization of human breast cancer xenografts is high. Tissue oxygenation in microareas of human breast cancers xenotransplanted s.c. into nude rats is mostly inadequate. As a consequence, tissue hypoxia and anoxia are common findings even in very early growth stages. Due to marked intra- and intertumor variabilities in blood flow, heterogeneities in the tissue oxygenation are characteristic features of human breast cancer xenografts. From the results obtained it is concluded that human breast cancers growing as xenografts in rnu/rnu rats may be useful tools for cancer research, especially for investigations of blood flow, tissue oxygenation, and substrate turnover.

Animals↗
PubMed1987

Tumour blood flow following local ultrasound heating computed from thermal clearance curves.

Thermal clearance curves following termination of ultrasound-induced hyperthermia in human mammary carcinomas implanted into the flanks of nude rats were studied. They were found to be monoexponential in form, both with and without blood flow. From the difference between the inverse time constants with and without flow, the tumour blood flow rate could be calculated. Blood flow was found to increase with very short exposure times at the therapeutic hyperthermia temperature and subsequently decrease as the exposure time increased. A higher therapeutic hyperthermia temperature augmented this effect.

Animals↗
PubMed1987

L-glutamine: a major substrate for tumor cells in vivo?

From 65 human breast cancer xenografts investigated, a net glutamine uptake was found in 13 tumors (mean +/- SE: 15.7 +/- 4.5 nmol/g per min) whereas a net release (22.5 +/- 3.3 nmol/g per min) was observed in 40 tumors. In 12 tumors neither a significant net uptake nor a net release was obvious. There is experimental evidence that glutamine is taken up by cancer cells only at arterial concentrations greater than 0.5 mM. Another parameter determining glutamine utilization by tumor cells may be the tissue oxygenation. In hypoxic or anoxic tumor areas, glutamine oxidation is unlikely since oxygen is required for the reoxidation of coenzymes which are reduced in the course of this metabolic pathway. The pronounced net release could be due to proteolysis within the tumors investigated. In ascitic fluid (DS-carcinosarcoma), glutamine accumulated during growth, implicating a reduction in the glutamine consumption rate, proposedly also due to a worsening of the oxygen supply to the suspended tumor cells. Thus, the generally held opinion that L-glutamine is a (if not the) major substrate for the energy metabolism of rapidly growing tumor cells should be reconsidered since evidence for this hypothesis has been derived mainly from in vitro systems with abundant oxygen.

Animals↗
PubMed1987

Is the division of heated tissue into temperature equivalent zones suitable for estimation of tumor blood flow from thermal clearance curves?

Problems arising during application of a method proposed recently to predict tissue blood flow from measured thermal clearance curves have been discussed here. In this method, the treated tissue is divided into temperature equivalent zones with the aim to improve the mathematical description of experimental washout curves compared to descriptions based on monoexponential temperature decay. However, when applying the mathematical procedure suggested, any blood flow can be calculated by variation of the number of isothermal zones chosen. Unfortunately, to date no method for determination of the proper division of the treated tissue into temperature equivalent zones is available. Thus, any choice of the number of temperature equivalent zones is arbitrary. Therefore, we suggest that other investigators should not follow the analysis recently proposed for the determination of blood flow from thermal washout curves.

Humans↗
PubMed1985

Human mammary carcinomas in nude rats--a new approach for investigating oxygen transport and substrate utilization in tumor tissues.

A new model is presented for the study of oxygen supply and substrate utilization in human tumor tissue. In this approach human tumor material thrives in immune-deficient nude rats. The host chosen allows the continuous evaluation of all relevant parameters. From the data obtained so far it is concluded that this model is a valid tool in investigation of the metabolic status of human tumors.

Animals↗
PubMed1985

Blood flow and oxygen supply to human mammary carcinomas transplanted into nude rats.

Blood flow of human mammary carcinomas heterotransplanted into immune- deficient rnu/rnu-rats is low. It decreases further with increasing tumor wet weight, the mean value being comparable to that of mammary carcinomas in patients. The O2 consumption rate of the heterotransplanted tumors decreases with increasing tumor wet weight and again is comparable to that of mammary carcinomas in patients. Furthermore, it is directly proportional to the O2 availability which in turn is mainly determined by TBF. The O2 utilization of the human mammary carcinomas heterotransplanted into nude rats is already high in small tumors and increases only slightly with increasing tumor weight. From these results and taking into account an impairment of convective and diffusive O2 transport it can be concluded that the O2 consumption rate of the tumor cells is mostly determined by the the O2 supply and not by the actual demand of the cancer cells. This finding holds true for different tumor cell lines in different species.

Animals↗
PubMedDate not supplied

Factors governing hyperthermia-induced pH changes in Yoshida sarcomas.

The impact of various factors modulating the acidification of tumour tissue upon localized ultrasound hyperthermia (1.7 MHz) at 44 degrees C for 60 min was investigated. Yoshida sarcomas were implanted into the hind foot dorsum of Sprague-Dawley rats. Frequency distributions of tumour tissue pH values were measured with miniaturized needle glass pH electrodes (diameter of the sensitive tip: 650 microns). During normothermia the average tumour pH is 6.87 +/- 0.21. No relationship is found between tumour pH and tumour size (range: 0.6-5.4 g). A pH gradient exists from the tumour periphery (0.5-3.5 mm) to more central tissue layers (7.5-10.5 mm; delta pH = 0.17). During hyperthermia with heating-up rates greater than 1.5 degree C/min, mean tumour pH drops to 6.71 +/- 0.20 considering all tumours. The pH reduction observed is size-dependent being most pronounced in medium-sized tumours (wet weights around 2.4 g, delta pH = 0.26). Using the same tumour sizes, but heating-up rates less than 0.7 degree C/min, the tissue acidification is more severe (delta pH = 0.40). To a small extent, pH changes also depend on the tumour region investigated (e.g. central vs. peripheral tissue layers) leading to a flattening of the pH gradient from the tumour shell to the centre during heat treatment. During hyperthermia an interstitial oedema occurs, being mostly marked in small tumours (around 1.4 g). Considering systemic changes, a transient increase in perfusion pressure (leading to a change in blood flow), as well as a slight elevation of blood glucose levels (leading to a higher glucose supply), during hyperthermia may contribute to the pH drop.

Animals↗
PubMedDate not supplied

Prevalence of enteropathogenic bacteria in surgically treated chronic inflammatory bowel disease.

BACKGROUND/AIMS: In order to assess the potential impact of bacterial eradication on recurrence rates, the prevalence of various enteropathogenic bacteria and toxins in chronic inflammatory bowel diseases (CIBD) was prospectively examined. METHODOLOGY: Stool, sera and gut tissue samples from a total of 59 patients (33 males, 26 females; mean age: 42 years +/- 14; 21 Crohn's disease, 14 ulcerative colitis, 24 controls) were examined for the presence of enteropathogenic bacteria by culture, immunoblotting and PCR. RESULTS: Conventional cultures failed to detect obligate pathogenic bacteria. By PCR, mycobacteria were found in 85% of all groups, with mycobacterium paratuberculosis not detected. Yersinia species were observed in 63% of patients with Crohn's disease, in 46% of patients with ulcerative colitis, and in 36% of the control patients. Pathogenic E. coli were identified in stool samples of three patients with ulcerative colitis (21%) by amplifying the EAE-gene, one of whom exhibited shiga-like-toxin as well. CONCLUSIONS: We concluded that mycobacteria do not play a causative role in CIBD. Yersinia species seem to persist in intestinal tissue in CIBD patients without adequate immune response and might, thus, contribute to tissue destruction. E. coli infections contribute to the disease process in a small group of patients with ulcerative colitis and their eradication might eliminate the need for immediate surgical intervention.

Adult↗