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Biomedical subjects

H Krug

Publications and source records attributed to H Krug.

At least 19 recordsLinked to original sources

A new simulation approach for the determination of the error of parameters of biological importance describing the growth of the Ehrlich ascites tumor of the mouse.

Some aspects of the growth of the Ehrlich ascites tumor of the mouse can be described by the logistic function. The parameters used are fitted to the experimental data in a nonlinear way. It is important to determine the error of these parameters of biological importance in order to discriminate between different consequences induced by various experimental situations by means of statistics. But often there is a gap between the data that are available and the stronger assumptions necessary for statistics. We propose a simulation approach which also works in a much larger range of similar situations to close this gap.

Animals

[Degree of DNA ploidy and steroid hormone receptors as prognostic factors in endometrial carcinoma].

In a prospective investigation the concentration of DNA (ploidy) and of steroid hormone receptors (ER and PgR, resp.) were studied in endometrial carcinoma and related to each other, to established morphological prognostic criteria (stage, typing, grading, relative invasion of myometrium), and to the clinical progress of disease, respectively. The microscopic spectrophotometric analysis of DNA showed diploid main lines in 2/3 of investigated endometrial carcinoma. It could be demonstrated a relationship between heteroploidy, decreased mean concentrations of ER and PgR, unfavourable prognostic factors (stage II-IV, G3, myometrial invasion of greater than 2/3) and clinical progress of disease. The mean value of ER and PgR was higher in diploid carcinoma than in heteroploid ones. Significant differences were found both in the relation of the PgR concentration to different tumor stages (stage I vs. II-IV) and of the concentration to the different types of ploidy. Exceeding the histological differentiation, the determination of DNA and ER/PgR receptors can results in additional prognostic informations for a scientific proved, adjuvant or curative strategy of therapy after the operation.

Carcinoma

[Cytophotometric studies for evaluating the prognosis in endometrial cancer].

This paper deals with a prospective cytophotometric study of specimens from 48 cases of primary endometrial carcinoma. The tumor material was obtained from the region of tumor invasion immediately after an operation and in 8 cases by fractional curettage after ultrasonographic localisation of the tumor. The specimens were air-dried and Feulgen stained. The cytophotometric examinations were performed with a scanning cytophotometer. A computer-assisted data registration and processing was carried out. The histological diagnosis of the tissue specimen and curettage specimen was established according to standardized criteria. 32 out of the 48 investigated cases of endometrial carcinoma were diploid. Observations conducted over a period of 12 months showed a partially significant correlation (u-test according to Mann and Whitney) between DNA-content and stage of the tumor (FIGO), histological grade of the tumor, relative depth of myometrial invasion as well as the clinical course. A differentiation based on the ploidy and the average relative DNA content (AE) in relation with typing is not possible. It was not possible to state the difference between average nuclear surface (F) and individual morphological variables. The average extinction, as a measure of the chromatin density, was determined for each specimen. A significant increase of the average extinction was established for carcinomas which infiltrated more than 2/3 of the uterine wall. Ploidy, average relative DNA content and average extinction provide an invaluable additional parameter in the assessment of the prognosis, post-operative therapy and aftercare of patients with endometrial carcinoma.

Adenocarcinoma

[The growth of the skeleton, body mass and muscle fiber diameter of the turkey (Meleagris gallopavo) from hatching to the 224th day].

Growth of body mass, femur, tibiotarsus, and tarsometatarsus length as well as the diameter of muscle fibers in the M. pectoralis were measured in (Large White) female turkeys between birth and day 224. Growth-specific approximations were established with the Janoschek function as modified by Sager (1978) and with the Logistic function. While the Janoschek function fairly described the growth of the turkey, the Logistic function throughout gave beginning values that were too high and theoretical end values that were too low. Of the five growth parameters that were measured, the diameter of the muscle fibers showed its maximal rate of growth first on day 21. The following decrease in growth rate took the following sequence: length of tarsometatarsus, femur, and tibiotarsus, diameter of muscle fibers, body mass. 99% of growth had occurred in the tarsometatarsus length on day 109, femur length on day 117, tibiotarsus length on day 138, diameter of muscle fibers on day 166, and the body mass on day 231. A comparison of this growth with that of other domestic fowl showed close relationships between the way turkeys and chickens grow.

Animals

[DNA distribution and mitotic index in Ehrlich ascites tumor after colchicine administration].

Additional information like the type of growth is efficient for the interpretation of single parameter DNA distribution curves of tumors. The consideration of mitotic indices leads to further insights. The different growth phases of the Ehrlich ascites tumor are characterized by reproducible DNA histograms. The mitotic index and the frequency of the four mitotic phases turn out to be independent of the growth phase. Colchicine exerts an obvious effect on the prophases and metaphases. In the histogram an accumulation of cells in the G2M phase is evident, also on a higher ploidy level. Nearly identical DNA histograms result in different growth phases. The mitotic index of prophases and metaphases is found to be nearly twice at the 11th and 15th day of growth in comparison with the 8th day. This indicates a higher sensitivity of the Ehrlich ascites tumor to colchicine in steady state which is not expressed in the histogram.

Animals

[Proliferation kinetics of Ehrlich ascites tumors during cisplatin administration].

In order to study the relationship between numerical growth and DNA-frequency distribution of tumor cells model experiments were made on the Ehrlich ascites tumor of mice after a single doses of the cytostatic cis-Platin. In 84 mice the tumor growth was measured by cell counting and the DNA-histogram by flow-cytometry. With exception of the controls 4, 8, 16 mg cis-Pt/kg were applied i.p. at the 5th day of tumor growth. An inhibition or a retardation of tumor growth is always observed. The 4 mg doses leads to a G2-blockade resulting in an increase of the G2-peak in the DNA-histogram after 2 days (7th day of growth). After 7 days of tumor growth) the effect has been mainly subsided. The effect of 16 mg/kg is a blockade of G2- and S-phase as well, connected with a complete inhibition of tumor growth. Therefore after two days (7th day of growth) this DNA-histogram is very similar to that of the control. Later on a recovery of DNA-synthesis occurs while the G2-blockade is still existing. Therefore the G2-peak is very marked 7 days after application (12th day of growth). All doses result in a disturbance of higher ploid cycles with an increase of hyper-8c-nuclei.

Animals

[Cell cycle and catamnesis in breast cancer. Cytophotometric studies].

Based on flow cytometry (120 cases) and scanning cytophotometry (56 cases) prognosis turns to the worst in the sequence diploid - polyploid - aneuploid tumors and with increasing S- and G2M-compartments. Principally the same correlation exists to other prognostic signs as lymphatic metastases, tumor size and histological grading.

Breast

Histophotometry--the method of choice in quantifying dehydrogenase histochemistry.

Succinate, malate, and lactate dehydrogenase were demonstrated histochemically and measured histophotometrically in the heart and skeletal muscle (m. extensor digitorum longus and m. soleus) of rats at different ages. To prove the value of histophotometry, the enzymes of the tissues were estimated biochemically. The gel film technique cannot sufficiently prevent the diffusion of the soluble enzymes (malate-, lactate dehydrogenase) out of the tissue sections. Because of the different mobility, various isoenzymes, histophotometry cannot give reliable results. But, as far as membrane-bound dehydrogenases (succinate dehydrogenase) are concerned, histophotometry is the method of choice for basic measurements as in routine practical work, especially with tissues where the enzyme activities are heterogeneously distributed, e.g. in different types of muscle fibres in skeletal muscles.

Aging

Progressive ankylosis (ank/ank) in mice: an animal model of spondyloarthropathy. II. Light and electron microscopic findings.

Murine progressive ankylosis was studied by light and electron microscopy (EM). By light microscopy, the earliest synovial lesion was inflammatory followed by synovial proliferation and cartilage erosions. Later changes included progressive joint ankylosis by fibrosis and ossification of articular and periarticular tissues and new bone proliferation. By EM, synovial cell proliferation and hypertrophy with collagen deposition was seen before the appearance of intracellular and extracellular hydroxyapatite crystals. These pathologic changes are the same as those found in the human spondyloarthropathies. Our EM findings demonstrate that hydroxyapatite crystals appear in the joints of ank/ank mice after the initial inflammatory phase.

Animals

Cytophotometric and interference microscopic investigations in carcinomas of the oral cavity.

The DNA content and the nuclear dry mass of 18 keratinized squamous cell carcinomas and their metastases, of one adamantinoma recurrence and two adenoid cystic carcinomas of the oral cavity were determined in comparison to the normal buccal mucosa using Feulgen scanning cytophotometry and interference microscopy. The squamous cell carcinomas could be classified into five groups based on their DNA distribution pattern. The nuclear dry mass and its variation were found to be different from the normal mucosal epithelial cells in all cases. No differences could be found between diploid cells and cells of a higher degree of ploidy. Therefore the relation of nuclear dry mass and DNA content appeared to be lower in cells of higher DNA ploidy. This fact is discussed in relation to the underlying molecular biological processes. This leads to the conclusion that the increase of the nuclear dry mass (mainly protein) precedes the increase of the DNA content. The combined measurement of DNA content and nuclear dry mass allows a better characterization of malignancy than each of the nuclear components measured alone. The difference of nuclear dry mass between malignant cells and normal mucosal epithelial cells is more sensitive than the deviation of the DNA content owing to the fact that malignant tumours with normal DNA content exist.

Carcinoma, Squamous Cell

[Age changes of functional nuclear swelling and classes of nuclei in human hepatocytes].

The aim of the study was to describe aging changes in the functional nuclear edema and the classification of human hepatocyte nuclei, by determining three parameters--the size of the nucleus, the relative DNA quantity and the number of chromocenters. For this purpose, karyometry and DNA cytophotometry were performed on 10 human liver preparations. The data obtained was subjected to correlation, cluster and discriminance analysis. The results indicated a reduction in the capacity of liver cells for functional nuclear edema as aging progressed. Whereas at a young age there is only a loose correlation between nuclear size and DNA content, it becomes much stricter later on, partly caused by polyploidization. Cluster analysis, followed by discriminance analysis, is well suited for dividing the nuclei of human hepatocytes into two or three statistical populations provided the nuclear area, DNA quantity and number of chromocenters are all used as characteristics simultaneously. When allowance is made for functional edema, the biological interpretation of clusters from young liver preparations permits meaningful conclusions, but it appears problematic for old preparations. Here it might be more practical to analyze the mixed distributions resulting from a determination of the DNA quantity or nuclear size alone.

Aging

Progressive ankylosis in mice. An animal model of spondylarthropathy. I. Clinical and radiographic findings.

To determine its similarity to human spondylarthropathies, we studied murine progressive ankylosis, a spontaneously occurring disorder of joints in mice. Clinically, peripheral joints were inflamed initially, then became ankylosed in a predictable sequence from distal to proximal. Forefeet were involved before hindfeet. Axial joint involvement produced severe spinal ankylosis. Extraarticular manifestations included balanitis and crusting skin lesions. Radiographically, bony erosions and calcification of articular and periarticular tissues were extensive, and vertebral syndesmophytes produced a "bamboo" spine. We conclude that progressive ankylosis is a systemic disease with many clinical and radiographic similarities to human spondylarthropathies, and it may represent a useful animal model for the study of the human diseases.

Animals

Flow cytometric DNA histograms and type of growth.

DNA histograms of human tumors should be interpreted together with the type of growth. In order to prove this connection the Ehrlich ascites tumors of 144 mice were investigated by absolute cell counting and flow cytometry. The exponential, transition and steady-state phases of tumor development were defined as types of growth based on the logistic function (Verhulst-Pearl). Flow-cytometric histograms (ethidium-bromide, olivomycin) were evaluated by two methods presupposing lognormal distribution and resulting in the same trend of changes concerning the percentage of cells in the three cell-cycle phases. In exponential growth the histograms show a high S-phase compartment and a decrease of the G2M peak. The increased percentage of S-phase cells is caused by a recruitment from G0-1 and G0-2 after transplantation. The decrease of the G2M peak is due to the exponential growth, a recruitment from G0-2 and a relative shortening of G2M duration. A high G2M peak and a low S-phase portion occur in steady state. Besides a decrease of DNA-synthesizing cells the S compartment decreases as a result of a relative S-phase shortening. For the increase of the G2M peak, transition into steady state, prolongation of G2M duration, recruitment of G0-1 and the occurrence of G0-2 cells are responsible. The same histogram may reflect different biological behavior patterns depending on the type of growth.

Animals

Stimulation of arachidonic acid metabolism via phospholipase A2 by triethyl lead.

Human blood platelet aggregation and the formation of icosanoids were studied in response to triethyl lead chloride (Et3PbCl). Concentrations higher than 75 microM stimulate platelets to aggregate, whereas low concentrations (less than or equal to 20 microM) caused platelet hypersensitivity to aggregating agents such as collagen or arachidonic acid. Incubation of suspensions of washed platelets with Et3PbCl resulted in a stimulated liberation and subsequent metabolism of arachidonic acid. This response was dependent on the concentration of Et3PbCl and the incubation time. Using low concentrations of Et3PbCl and up to 3 h of incubation, the lipoxygenase product 12-hydroxy-5,8,10,14-icosatetraenoic acid was the major metabolite. Under normal conditions, however, stimulation of platelets with collagen, thrombin, or arachidonic acid leads to higher amounts of the cyclooxygenase products 12-hydroxy-5,8,10-heptadecatrienoic acid and thromboxane B2. The aggregation of human platelets induced by Et3PbCl was inhibited by three different drugs: acetylsalicylic acid, forskolin and quinacrine; but only quinacrine could prevent the liberation of arachidonic acid and the appearance of its metabolites. These specific effects of the inhibitors on Et3PbCl-stimulated platelets as well as the differences in the pattern of arachidonic acid metabolites and phosphatidic acid suggest a direct stimulatory action of Et3PbCl on platelet phospholipase A2.

Arachidonic Acid

Dry mass, DNA and non-histone protein determinations in lung cancer cells.

Cell nuclei from two biopsies of bronchial mucosa, seven squamous-cell carcinomas and six small-cell carcinomas of the lung were investigated. DNA and non-histone protein (NHP) content were simultaneously determined in Feulgen-Naphthol Yellow S-stained smears by means of multiple plug cytophotometry. In addition, the nuclear dry mass of cells originating from the same populations was measured by interference microscopy. DNA histograms of carcinomas were characterized by DNA stemlines being situated in the diploid range in four out of six small-cell carcinomas and in the hyperdiploid to hypertetraploid range in six out of seven squamous-cell carcinomas. Polyploid values (up to 8 c) were seldom found in small-cell carcinomas whereas squamous-cell carcinomas showed a broader dispersion approaching the 16 c level. The similarity of the NHP distributions with the DNA histograms was more marked in small-cell carcinomas than in the squamous-cell carcinomas. In comparison with the NHP distributions of normal bronchial epithelial cells, those of carcinomas were shifted to higher values. The increased NHP content was found to be a more prominent sign of malignancy in small-cell carcinomas than the DNA mass. The increase in nuclear dry mass in carcinomas was mainly caused by the accumulation of NHP in tumour cell nuclei.

Bronchi

Histophotometrical measurements concerning the distribution of myofibrillar ATPase activity within the tissue block after aldehyde fixation.

The inhibition of myofibrillar ATPase activity by aldehyde fixation in tissue pieces of myocardium of the rat was measured by scanning histophotometry. The relative amount of the final reaction product of the histochemical method for ATPase (Padykula and Herman 1955) was taken as a measure for the enzyme activity. Along scanning lines in slides from the surface to the centre of tissue block, a higher activity was found in the centre in contrast to the marginal zone. Compared with the centre of the block (approximately equal to 100%), in the marginal region a loss of about 40% (in paraformaldehyde PFA) and of 75% (in glutaraldehyde GA) was found, the latter with a sharp decline between the marginal zone and the central part. For quantitative enzyme histochemistry by histophotometry unfixed material is recommended.

Adenosine Triphosphatases