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PubMedDate not supplied

[Herpes simplex virus and malignancies of female genital organs].

INTRODUCTION: Primary herpes simplex virus (HSV) infections of female genital tract usually end with remission, while the virus remains in the organism--almost in the sacral ganglion in a latent form, protected from humoral and cellular immunity. Stress induces the virus and the result is recurrent genital infection. Frequent exacerbations damage some parts of vital cellular structures without cytolysis, but stimulate malignant transformations. MATERIAL AND METHODS: Vulvar (portio vaginalis uteri) and endometrial tumor tissue samples were analyzed for HSV by direct and indirect fluorescent antibody technique (FAT). Pre and postoperative sera samples were analyzed for presence of anti-HSV antibodies--IgM and IgG by Elisa-Enzygnost method. Acellular filtrates obtained by ultrasonic destruction of malignant tissues were used as inoculum for rabbit corneal scarification. RESULTS AND DISCUSSION: Out of 63 tissue samples, 42 were positive for HSV antigen i.e. 67.3%. According to location 50% of vulvar, 76% PVU and 65% of endometrial tissues were positive. This antigen induces production of virus specific antibodies. Two types of antigens are known: the so-called T-antigen persisting in the cell nucleus and cell-surface antigen--product of the viral genome and can be evidenced by immunofluorescence method. Anti HSV antibodies were present in 63 preoperative serum samples and belonged to IgG group, but not one to IgM, implying a long and chronic course of infection excluding acute primary. Out of 38 postoperative serums the titer of antibodies decreased in 36 evidently, but in two samples remained unchanged. Two samples of endometrial and one from PVU origin contained HSV antigen type one. In the remaining 16 samples HSV 2 antigen was present. Rabbit corneal scarification was the proof of complete infectious virus in malignant tissues. Acellular filtrate of malignant tissues served as inoculum. Corneas of examined rabbits showed a mild inflammation after 24 hours which disappeared in the next 24 hours. We could not isolate the infectious virus by rabbit corneal scarification. Instead of herpetic changes, mild inflammation was evident. This abortive, incomplete symptomatology was probably caused by nonstructural early protein, which is a product of viral genome incorporated in malignant cells. CONCLUSION: On the basis of our results, we can conclude that HSV can have, beside other factors, a very important, maybe an initial role in development of malignant changes of female genital tract, not only on vulva and PVU, but on endometrium as well. HSV I can cause genital infections and have some role in malignant changes as well as HSV 2. However, complete infective virion couldn't be isolated from malignant tissues.

Adult↗
PubMed2002

Marked prevention of tumor growth and metastasis by a novel immunosuppressive agent, FTY720, in mouse breast cancer models.

FTY720 is a unique immunosuppressive agent that exerts its activity by inducing apoptosis in lymphocytes. We conducted the present study to investigate the effects of FTY720 on cancer growth and metastasis, as well as its mechanism of action. In vitro treatment with FTY720 induced dramatic cancer cell apoptosis in a mouse breast cancer cell line, JygMC(A). Electron microscopy revealed distinct changes on the cell surface with decreased filopodias and microvilli in cancer cells treated with FTY720 at 2 microM and clear evidence of apoptosis at 10 microM. Interestingly, the effect of FTY720 was significantly less in the normal fibroblasts than in the cancer cells, indicating greater susceptibility of cancer cells to the agent. We then tested the in vivo effect of FTY720 in a mouse breast cancer model created by inoculating JygMC(A) cells (s.c.) in the flank region of BALB/c-nu/nu mice at three different dosages (2, 5, and 10 mg/kg/day; n = 30/group). Tumor growth was markedly suppressed at a dosage of 5 mg/kg or more without notable side effects. In addition, tumor metastasis, which was dramatically evident in control mice, was significantly prevented even at a low dose (2 mg/kg/day), resulting in a significant prolongation of animal survival. These data led us to additionally investigate the mechanism of action, especially the prevention of metastasis at a low dose. FTY720 treatment at 2 microM caused a remarkable cytoskeletal change with deformed and decreased filopodias in cancer cells. In addition, it significantly decreased the ability of cancer cells to adhere and migrate to extracellular matrix components, and markedly reduced the expression of integrins on the cancer cell surface. These results indicate that FTY720 is a potent anticancer agent that induces cancer cell apoptosis and is markedly effective for prevention of metastasis. The changes of cellular structure with reduction of integrin expression may be one of its underlying mechanisms of action.

Actins↗
PubMed1975

[A contribution to the pathophysiology of post-traumatic brain oedema (author's transl)].

The aim of this paper is to contrast new results obtained on the activities of lysosomal proteases in the brain of traumatized animals with the previously held opinions concerning the development of post-traumatic brain oedema. Two hours after a standardized head injury in the cat, acid and neutral proteases were determined in the brain homogenate. Total as well as free activity, especially of the neutral proteases, were markedly increased after head injury, a circumstance indicating the important role of lysosomes in the development of post-traumatic brain oedema. It is postulated that not hypoxia alone, but primary or secondary disturbance of lysosomal function is the predominant factor in the development of brain oedema. Release of enzymes -- especially proteases -- causes irreversibility of initial vascular oedema by autolysis of cellular structures.

Animals↗
PubMed1975

A freeze-etch study of occurrence of nuclear pores in normal and tumor cells.

A freeze-etch study of nuclear pores performed on human lymphocytes, epidermal and corneal cells, on hamster fibroblasts, on rat and hamster sarcoma cells and cells from a human malignant melanoma, revealed that the frequency of pores as a part of very important biological cellular structures increases in proliferating cells, and that there is a statistically significand difference between normal and tumor cells. Once produced the pores maintain and their frequency practically does not change. The pores are randomly distributed on the nuclear envelope. Markham rotating method revealed an octa- or nonaedric outside shape of the pores and round inner margin with eight or nine granules. One bigger granule was found in the center of the pores. The granule is with a great probability filamentously attached to the margin of the pore. Fibrillar structures running to the pores on inner surface of nuclear envelope as far as the chemical composition of granules need special cytochemical examinations.

Animals↗
PubMed2002

Trypanocidal action of 2,4-dichloro-6-phenylphenoxyethyl diethylamine hydrobromide (Lilly 18947) on Trypanosoma cruzi.

AIM: To study the effect of the inhibitor of cytochrome P450 known as Lilly 18947 (2,4 dichloro-6 phenylphenoxy ethyl diethylamine) on Trypanosoma cruzi. METHODS: Trypanosoma cruzi epimastigotes were grown in culture, in absence or in presence of drug. The inhibition of its growth was followed by daily counting using a Neubauer chamber. The effect of Lilly 18947 on the parasite ultrastructure was examined by electron microscopy. To test the effect of different concentrations of drug on the parasite cycle, Vero cells were inoculated with trypomastigotes (RA strain) and after 72 h the percentage of infected cells and the number of intracellular parasites were estimated and expressed as the endocytic index. RESULTS: Growth of epimastigotes was inhibited by Lilly 18947. Concentrations as low a s 50 micromol/L resulted in a complete disappearance of the parasites in culture by the fourth day. With lower concentrations, little growth was observed and total (25 micro mol/L) or partial lysis (10 micromol/L) were registered by the eighth day of culture. Incubation of epimastigotes with 50 micromol/L of Lilly 18947 resulted in an early damage to cellular structures. Initial signs were dilatation of perinuclear membranes and mitochondria swelling. The infectivity of trypomastigotes to Vero cells in culture was nearly abolished at 15 and 30 micromol/L concentrations of the drug. CONCLUSION: Lilly 18947 was able to harm Trypanosoma cruzi membrane functions leading to t he loss of its infective properties and its death.

Animals↗
PubMed2001

[Light effect at various wavelengths on gametogenesis of the Black Sea sea urchin (Strongylocentrotus nudus)].

Comparative study of the effect of light at wavelengths of 720 and 520 nm on the reproductive process in black sea urchin Strongylocentrotus nudus was performed in artificial conditions. The results obtained not only suggest the distinct influence of light on the reproductive process in sea urchin, but also indicate that its effects on oogenesis and spermatogenesis are different. Light at the wavelength of 720 nm was found to activate gonad development, while at the wavelength of 520 nm it had a suppressive effect by decreasing the oogonial and spermatogonial content without disturbing their cellular structure. It is proposed that the gametes which are formed in sea urchins that are exposed to the light with differing wavelengths may possess different capacities for reproduction, thus influencing the viability of the young.

Animals↗
PubMed1979

Radiolabeled liposomes as metabolic and scanning tracers in mice. II. In-111 oxine compared with Tc-99m DTPA, entrapped in multilamellar lipid vesicles.

We describe the organ distribution of positively and negatively charged multilamellar lipid vesicles (MLV) labeled with Tc-99m DTPA or In-111 oxine in mice. The organ distribution of MLV (In-111 oxine) is fairly constant throughout 72 hr, indicating that the radiotracer remains associated with cellular structures at the site of MLV uptake. In animals injected with MLV (Tc-99m DTPA), on the other hand, there is continuous leakage of radioactivity from the involved organs. This can be explained by the release of the radiotracer following MLV destruction in the organs. MLV (IN-111 oxine) may be used to study MLV uptake by different organs, whereas MLV (Tc-99m DTPA) may be a good indicator of the destruction rate of lipid vesicles. Various conditions bearing on liposome kinetics merit further study in order to assess the potentialities of these vectors as diagnostic or therapeutic agents.

Animals↗
PubMed2002

[Caspases and apoptosis: die and let live].

Apoptosis (genetically programmed cell death) plays a key role in human physiology and pathogenesis of various diseases, including cancer. A suicide of cell can be initiated by many different factors, but activation of caspases, which are a special class of proteolytic enzymes, is always involved in this process. Activation of caspases may be achieved by several molecular pathways: the best known stimuli triggering caspase cascade are stimulation of Fas or TNF receptors, release of cytochrome c from the cellular mitochondria and exposure to granzymes, which are secreted by cytotoxic T cells. Activated caspases digest many cellular proteins responsible for cell cycle regulation (e.g. RB, MDM2), DNA damage recognition and repair (e.g. DNA-PK, P53, PARP), and regulation of the cellular structure (e.g. actin and lamins). All these functional and structural protein modifications lead directly to apoptosis. Further research on the mechanisms controlling caspase activity and the modes of action will provide better insight into pathogenesis of cancer and other disorders. It may be even the first step to design new and more efficient methods of conventional tumor treatment or gene therapy.

Animals↗
PubMedDate not supplied

[Natural toxins in inter- and intraspecies interaction of human being (elements of ethnotoxinology)].

The author considers the application of natural toxins as arrow poison by Homo sapiens from ancient time till today for hunting and ethnic wars on the example of natives of Asia, Africa, South America and Oceania. Geographic isolation was important determining the spectrum of natural toxin sources and the methods of their application. Cellular and molecular mechanisms of arrow poisons effects are considered in biogeographical context: aconitin and strychnin in Asia, diamphotoxin in Africa, indole alcaloids of plants and steroid alcaloids of amphibian in Central and South America, palytoxin in Oceania islands. High efficiency and selective effect of natural toxins allow to use them as molecular markers in current studies of functional membrane architecture and cellular structures. Great differences in pace of civilization development leads to the co-existence at the beginning of the XXI century ethnic groups that use natural toxins as arrow poison and human beings that use the same toxins in fundamental and applied investigations within international scientific society.

Aconitine↗
PubMedDate not supplied

[Ultrastructural characteristics of the adrenal gland].

The Adrenal glands can be viewed as sustaining vital processes in the human body, through two different but related components: the cortex and the medulla. It is well known that the close connection between the cortical cells is able not only to support the adrenal functions, but in the same time to serve the better understanding of the normal way of its hormonal production. Using the ultrastructural study of the adrenal gland, we obtain images which can provide informations about details of the cellular structure, in the eventuality that all this work will continue to improve to the point that we might be able to completely understand the complex interrelations between the structure of each cell and the function of the whole organ.

Adrenal Glands↗
PubMed1975

[An autoradiographic study of adenocarcinoma of the stomach].

Sixteen cases of human stomach adenocarcinoma were studied, using the in vitro incubation in H3-thymidine medium. The portion of cells synthesizing DNA (the label index) has been correlated with histological and clinico-anatomical characteristics. An average value of the label index for human stomach adenocarcinomas was 29.9% (14.1%--39.1%). Some dependence between the label index and level of structural-cellular atypism of tumor tissue and tumor size has been shown.

Adenocarcinoma↗
PubMed2002

Biodegradable polymer grafts for surgical repair of the injured spinal cord.

PURPOSE: Biodegradable polymers have been used in the surgical repair of peripheral nerves, but their potential for use in the central nervous system has not been exploited adequately. This article discusses concepts related to the engineering of a biodegradable polymer graft for surgical repair of the injured spinal cord and explores the potential means by which such a device might promote axon regeneration and functional recovery after spinal cord injury. CONCEPT: A biodegradable polymer implant with controlled microarchitecture can be engineered, and its composition can be optimized for implantation in the spinal cord. RATIONALE: The use of a biodegradable polymer implant has the dual advantages of providing a structural scaffold for axon growth and a conduit for sustained-release delivery of therapeutic agents. As a scaffold, the microarchitecture of the implant can be engineered for optimal axon growth and transplantation of permissive cell types. As a conduit for the delivery of therapeutic agents that may promote axon regeneration, the biodegradable polymer offers an elegant solution to the problems of local delivery and controlled release over time. Thus, a biodegradable polymer graft would theoretically provide an optimal structural, cellular, and molecular framework for the regrowth of axons across a spinal cord lesion and, ultimately, neurological recovery. CONCLUSION: Biodegradable polymer grafts may have significant therapeutic potential in the surgical repair of the injured spinal cord. Further research should be focused on the bioengineering, characterization, and experimental application of these devices.

Absorbable Implants↗
PubMedDate not supplied

Oxidative stress and congestive heart failure.

Oxygen free radicals, produced by the reduction of oxygen during many cellular reactions, have been implicated in the pathogenesis of a variety of cardiovascular diseases. Extremely reactive, free radicals damage many cellular structures and interfere with multiple cell functions. Clinically, free radicals have been associated with coronary atherosclerosis, ischemia, and reperfusion injury (“stunning”), and other processes related to chronic myocardial dysfunction. Several studies have reported elevated markers of free radical mediated injury in patients with congestive heart failure (CHF), and the link between oxidative stress and the genesis and progression of chronic CHF is being increasingly explored. This review briefly highlights free radical biology and examines the rationale and evidence for the role of oxidative stress in chronic heart failure. (c)1999 by CHF, Inc.

Journal Article↗
PubMed1975

[Cytologic diagnosis of different histologic forms of lung cancer].

Parallel cytological and histological investigations in 511 patients with of the lung cancer confirmed the possibility of verification of a tumour form on the basis of cytological preparations. Determination of cancer forms is carried out on the basis of the same principle criteria which are used in a histological investigation. The first stage of diagnosis consists in search for cellular, structural and functional signs of epidermoid and glandular differentiation. In the absence of these, there are grounds to consider the diagnosis to be non-differentiated cancer with subdivisions into micro- and macrocellular variants. Squamous-cell carcinoma with cornification highly differentiated adenocarcinoma and non-differentiated microcellular cancer possess characteristic features ensuring a highly reliable-cytological diagnosis. Cytological diagnosis of squamous-cell cancer was correct in 95.3% of cases, that of non-differentiated microcellular cancer-in 87.1%, and that of glandular cancer-in 81.2% of cases. The majority of errors made in verification of squamous-cell and glandular cancer were made with respect to their poorly differentiated forms which have no reliable cytological characteristics. The last statement is also true with respect to non-differentiated macrocellular cancer of the lung.

Adenocarcinoma↗
PubMed1999

Culture in vector-averaged gravity environment in a clinostat results in detachment of osteoblastic ROS 17/2.8 cells.

Studies carried out in space flights and in altered gravitational environments have shown that exposure to altered gravity conditions results in alterations in cellular structure and function. In the present study, we used a clinostat to generate a vector-averaged gravity environment, and evaluated the responses of osteoblast-like ROS 17/2.8 cells subsequent to rotation at 50 r.p.m from 24 to 72 hr. We found that the cells started to detach during the first 24 hr of culture in clinostat, but not in stationary and horizontal rotation (the latter serving as a control for turbulence, shear forces and vibrations). At 24 hr, there was a significant decrease in the number of adherent cells under clino-rotation (2.75 +/- 0.5 x 10(5) in stationary culture versus 2.02 +/- 0.27 x 10(5) under clino-rotation), and 19.8% of adherent cells were trypan-blue positive when cultured in 2% fetal bovine serum. All the detached cells were trypan-blue positive. At 72 hr, the cells became confluent in all three groups. These results suggest that vector-averaged gravity could cause the death of osteoblasts during the first 24 hr of clino-rotation. We hypothesize that this cell death might play a role in the pathogenesis of osteoporotic bone loss as observed in actual space flight.

Animals↗
PubMed2002

A new stain for identification of avian leukocytes.

Differential staining of avian leukocytes was achieved within 6 min following brief fixation in a methanolic solution of C.I. acid red 360 followed by immersion in a mixture containing C.I. basic blue 41, C.I. basic blue 141, and C.I. acid red 52. Heterophils contained black angular and punctate granules. Eosinophils contained bright purple granules. Lymphocytes displayed red nuclei and blue cytoplasm. Monocytes contained red-brown nuclei and lavender cytoplasm. Basophils showed red-orange granules. Thrombocytes stained deep purple. Compared to traditional panoptic stains like Wright's or Giemsa's, the new staining method provides brighter colors, more precise details of cellular structures, and shorter staining time. Significantly, it facilitates identification of avian leukocyte species based on differences in color as well as differences in size and shape.

Animals↗
PubMedDate not supplied

A subset of caspase substrates functions as the Jekyll and Hyde of apoptosis.

Cleavage of caspase substrates is believed to be the commitment point that will lead a cell towards apoptosis. While the cleavage of some caspase substrates participates directly in the dismantling of the cell, others regulate the extent of caspase activation. In this communication, we discuss some recent findings indicating that two caspase substrates, MEKK1 and RasGAP, change their functions from anti- to pro-apoptotic as caspase activity increases. MEKK1 is a MAPK kinase kinase regulating the JNK MAPK pathway. As a full-length protein, MEKK1 generates protective signals (e.g. in cardiomyocytes), but potentiates apoptosis when cleaved by caspases. This switch is mediated by a translocation of the kinase activity from insoluble to soluble cellular structures. RasGAP is a regulator of Ras GTPase family members. As a full-length protein, RasGAP does not modulate apoptosis. However, low caspase activity readily induces the cleavage of RasGAP into an N-terminal fragment that generates potent anti-apoptotic signals. At higher caspase activity, the N-terminal fragment is further cleaved into two fragments that strongly potentiate apoptosis. RasGAP can, thus, be viewed as an apoptostat because it allows the cells to determine when caspases have been mildly activated to fulfill functions other than apoptosis or when caspases are strongly activated to mediate apoptosis.

Apoptosis↗
PubMed2003

Genetics and heart disease.

Production of genome sequence has recently skyrocketed with many advances in the understanding and etiology of certain diseases. Researchers have localized a region of the human genome that plays a role in determining a persons susceptibility to myocardial infarction. A new apolipoprotein gene that influences triglyceride levels in humans is also described. A recent study from Finland showed that certain families are likely to carry a genetic form of insulin resistance syndrome that predisposes them to accelerated atherosclerosis. Researchers identified 3 mutations in the gene producing a protein called metavinculin, which appears to be linked to abnormalities in cellular structures and function in patients with dilated cardiomyopathy. Gene therapy has emerged as a genuine therapeutic option with the potential to alter the manner in which cardiologists manage the 2 most common cardiac disorders--coronary artery disease and congestive heart failure. Along with angiogenesis and gene therapy, cell transplantation is one of the newest treatment modalities proposed to improve the outcome of patients with cardiac failure. Two major advances in stem cell therapy for cardiovascular disease were published recently. They demonstrate how bone marrow stem cells can regenerate myocardium in the infarct area of a mouse heart. A German Cardiologist has for the first time successfully transplanted a patients own stem cells in an infracted area in the heart. This review summarizes the current knowledge of the genetic associations with cardiac diseases.

Animals↗