Biomedical subjects

M Markowski

Publications and source records attributed to M Markowski.

16 recordsLinked to original sources

PubMed2003

Role of ceramide in mediating apoptosis of irradiated LNCaP prostate cancer cells.

The sphingomyelin metabolites ceramide and sphingosine are mediators of cell death induced by gamma-irradiation. We studied the production of ceramide and the effects of exogenous ceramide on apoptosis in LNCaP prostate cancer cells that are highly resistant to gamma-irradiation-induced cell death. LNCaP cells can be sensitized to gamma-irradiation by tumor necrosis factor alpha (TNF-alpha) and, to a lesser degree, by the agonistic FAS antibody CH-11. TNF-alpha activated intrinsic and extrinsic apoptosis pathways and increased ceramide and sphingosine levels in irradiated LNCaP cells. CH-11 activated only the extrinsic apoptosis pathways and had a negligible effect on ceramide and sphingosine levels in irradiated LNCaP cells. Exogenous ceramide and bacterial sphingomyelinase sensitized LNCaP cells to radiation-induced apoptosis and had a synergistic effect on cell death after irradiation with TNF-alpha, but not with CH-11. Cell death effects after exposure to ceramide and irradiation were blocked by the serine protease inhibitor TLCK (Na-p-tosyl-L-lysine-chloromethylketone), but not by the caspase inhibitor z-VAD (2-val-Ala-Asp(oMe)-CH(2)F). During LNCaP cell apoptosis induced by exogenous ceramide, we observed activation of caspase-9, but not caspases-8, -3, or -7. The effect of ceramide occurred largely via the intrinsic mitochondrial apoptosis pathway and enhanced TNF-alpha, but not CH-11 effects on irradiated cells. The data show that ceramide enhanced activation of the intrinsic apoptotic pathway and enhanced cell death induced by TNF-alpha with or without gamma-irradiation. TNF-alpha and gamma-irradiation elevated levels of endogenous ceramide and activated the intrinsic cell death pathway.

Adenocarcinoma↗

PubMed2001

Androgen blocks apoptosis of hormone-dependent prostate cancer cells.

Androgen plays a critical role in the promotion and growth of prostate cancer. Androgen ablation has an expanding role in prostate cancer treatment and is now used to improve the efficacy of radiation therapy in addition to its role in treatment of metastatic disease. Here we show that androgen interferes with induction of prostate cancer cell death induced by a variety of stimuli. The effect of androgen on cell death occurs predominantly by interference with caspase activation and the inhibition of caspase cleavage in both the extrinsic and intrinsic cell death pathways. Androgen inhibited apoptosis induced by both tumor necrosis factor alpha (TNF-alpha) and by Fas activation with or without concomitant irradiation. An antiapoptotic effect was seen in the presence of R1881, dihydrotestosterone, and also 17beta-estradiol within 24 h of death induction. Sustained inhibition of apoptosis at 72 h was seen only with R1881, dihydrotestosterone, cyproterone acetate, and hydroxyflutamide. Androgen treatment inhibited activation of caspases-8, -7, and -9 by TNF-alpha +/- irradiation. Androgen attenuated BAX expression and blocked appearance of the proapoptotic p18 fragment of BAX. Androgen also abrogated BID cleavage induced by TNF-alpha + irradiation that contributed to a decrease in cytochrome c egress from mitochondria induced by TNF-alpha +/- irradiation. There was also decreased mitochondrial depolarization in response to TNF-alpha + irradiation. Production of the proapoptotic lipid metabolite ceramide was not affected by androgen, but androgen acted downstream from ceramide generation because R1881 blocked cell-death induction by bacterial sphingomyelinase. Inhibition of phosphoinositol-3-kinase activity by wortmannin induced apoptosis that was also blocked by androgen, but there was no effect on protein levels or phosphorylation of AKT, indicating that R1881 did not interact with survival signaling of phosphoinositol-3-kinase. Lastly, androgen inhibited activation of nuclear factor-kappaB during death induction, but the effect of androgen on cell death was not mediated by interference with the nuclear factor-kappaB pathway. The data suggest that androgen induced blockade of caspase activation in both intrinsic and extrinsic cell death pathways and thereby was able to protect prostate cancer cells from apoptosis induced by diverse stimuli.

Androgens↗

PubMed2001

Memory-enhancing effects of DHEAS in aged mice on a win-shift water escape task.

The steroid hormone, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been implicated in age-associated deficits in memory. Numerous studies have demonstrated the effectiveness of these neurosteroids to enhance retention and ameliorate the effects of various memory-blocking agents, but few studies have directly assayed their effects on memory in aged animals. The present study investigated the memory-enhancing effects of DHEAS in a win-shift (nonmatching-to-sample) task in aged mice using water escape motivation. Sixteen CD-1 mice, 18-20 months old, were trained to a moderate criterion of 7/10 correct trials and were then divided into two equal groups based on acquisition performance. One group received oral administration of DHEAS (1.5 mg/mouse/day) in a vehicle solution (0.0015% methyl salicylate) while the other group received the vehicle alone. DHEAS effects were assessed using a procedure in which delay intervals (0, 120, and 240 s) were interposed between sample and comparison trials over the course of three test sessions. The group receiving DHEAS recorded significantly higher retention scores across 3 days of testing, particularly at the 120-s delay interval, indicating that DHEAS enhanced working memory in these aged animals.

Aging↗

PubMed1999

In vitro effect of bioactive natriuretic peptides on perfusion pressure in placentas from normal and pre-eclamptic pregnancies.

The number of placental vascular guanylate-coupled receptors. corresponding to bioactive natriuretic peptide receptors is greater in preeclampsia. but there are no clear data about atrial natriuretic peptide (ANP) concentration in preeclampsia. The influence of various doses of ANP and urodilatin (URO) on placental perfusion pressure in preeclampsia was investigated by perfusing 16 human placentas in vitro. The placental vessels were submaximally preconstricted by continuous infusion of N-omega-nitro-L-arginine (NOLA). Perfusion pressure was measured continuously. Over 180 min various doses of alphaANP or URO were administrated (25, 50, 100, 200 nmol/l, 2 min increments). The effects of pretreatment with the guanylate cyclase inhibitor, LY 83583 was also examined. We found that ANP and URO attenuated NOLA-induced vasoconstriction, that URO given in higher doses produced stronger vasocilation than ANP, and that the mean decrease of perfusion pressure was higher in preeclampsia. The possibility of a non cGMP-mediated pathway of ANP and URO action should be considered.

Atrial Natriuretic Factor↗

PubMed1999

The role of Chlamydia trachomatis infection in cervical cancer development.

Previous Chlamydia trachomatis infection elevates expression of: 1. TGFalpha in CIN I, CIN II, CIN III; 2. HPV 16 in CIN I, CIN II, CIN III and invasive carcinoma; 3. Ki 67 in CIN III and invasive carcinoma. Chronic Chlamydial infection is very often associated with cervical hypertrophy.

Case-Control Studies↗

PubMed1998

Segmental pattern and nuclei in the human embryonic brain at stage 13.

Studies of serial sections and reconstructions of embryos at stage 13 (32) postovulatory days) revealed that the cranial neural tube in the investigated embryos possesses 15 neuromers: 1 telencephalic, 3 diencephalic, 3 mesencephalic, and 8 rhombencephalic. Within the primary efferent column all nuclei of the cranial nerves may be distinguished. Also fibers entering brain from cranial nerve ganglia form the common afferent tract. The relation of neuromers to the motor nuclei of the cranial nerves is following: M1-oculomotor, M2-trochlear, Rh2-trigeminal, Rh4-facial, Rh6-glossopharyngeal, Rh7-vagal, Rh8-hypoglossal.

Brain↗

PubMed1998

A case of high origin of the common interosseous artery.

During autopsy dissection a high origin of the common interosseous artery was found. The artery originated in the upper one third of the arm and followed the course of brachial artery. It gave off muscular branches and radial as well as ulnar recurrent arteries, and in the distal part of the cubital fossa it divided into anterior and posterior interosseous arteries. The brachial artery passed medially to the median nerve, gave off superior and inferior ulnar collateral artery, and above the superior border of the pronator teres muscle divided into ulnar and radial arteries.

Aged↗

PubMed1997

New protein and PCR markers RAK for diagnosis, prognosis and surgery guidance for breast cancer.

Breast cancer antigens RAK-p120, -p42, -p25 were detected in 100% of breast cancer cases tested (71 cases). Only 10% of adjacent tissue cases tested positive for all three cancer antigens, and 17.5% of the cases tested positive for two antigens only. Eighty-five percent of histologically normal breast tissue samples, isolated either from breast cancer patients or patients with advanced fibrocystic disease, tested RAK-negative, with the exception of low expression of p25, observed in some patients. Polymerase chain reaction (PCR) with HIV-1 gp 41-derived primers revealed cancer-associated DNA fragments of similar size (140 bp) as in HIV-1 genome. Fifty-four percent of cancer adjacent tissues, and 50% of malignancy-free breast tissue samples, tested PCR-negative. It is suggested that genetic predisposition to cancer may be associated with the presence of RAK genes, while expression of RAK antigens marks an already ongoing process of malignant changes.

Biomarkers, Tumor↗

PubMed1994

Surveillance for influenza in a newborn intensive care unit.

Although influenza may cause fatal neonatal infections, the current prevalence of disease in newborn intensive care units (NICU) is unknown. Furthermore, because compliance of NICU staff with annual influenza immunization is poor, absence of antibody may provide an indication of influenza susceptibility for neonatal patients and staff. We studied our NICU staff and patients during the winter of 1992-93 to determine seroprevalence of influenza antibody and attempted to document infection serologically or by culture in symptomatic staff and by culture in neonatal patients. Before the influenza season commenced or at birth (using cord blood), antibody to influenza A was absent in 9% (4/43) of the staff and 11% (9/83) of the neonatal patients. Antibody to influenza B was absent in 26% (11/43) of the staff and in 37% (31/83) of the neonates. We were able to document influenza serologically in only one nurse during the study. None of our staff or patients had positive cultures; however, we demonstrated a susceptible population of both staff and particularly neonates who need protection. There were study limitations of sampling and a low incidence of influenza in Connecticut for 1993. Nevertheless, continuing surveillance for influenza in NICUs could provide a more rational basis for immunization and prevention practices.

Adult↗

PubMed1994

The value of estimating CA 125 in fluids from benign or malignant cysts, in the exudate and blood serum in women with ovarian cancer.

CA 125 levels were estimated by immunoenzymatic technique: in fluids obtained by puncturing benign ovarian cysts under guidance of USG and in the patients' sera (23 cases); in serum and in ascites of 39 ovarian cancer patients at the IIIrd or IV th stage of clinical advance; in the content of malignant tumors in the course of surgery (in 16 of the above listed patients). Ca 125 level was significantly lower in the content of benign Cysts as compared to malignant ones. CA 125 level higher than 1000/ml pointed to a malignant process. Both in serum and in ascites, more advanced tumors and tumors showing progression manifested higher levels of the marker than less advanced tumors and tumors characterized as stable disease. In the group of patients analysis of CA 125 levels provided less information on the disease course than in individual cases.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1993

[Side effects of drug treatment for ovarian cancer after administration of antiemetic drugs].

The occurring frequency of 14 most common chemotherapy and anti-nausea drug side-effects was examined. The studies were performed on 29 women with ovarian cancer treated by total number of 125 chemotherapy courses (schedule PAC and Acy) and additionally, in order to eliminate nausea caused by the chemotherapy, by anti-nausea drugs (Zofran, Solu-Medrol, Droperidol, Metoclopramide + Fenactil, Torecan). Zofran caused the fewest number of side-effects, solu-medrol inhibited nausea and vomiting significantly, however it caused many side-effects such as flush on a face, restlessness, incitement and headaches. Torecan did not prevent patients from vomiting. The greatest number of side-effects was observed after droperidol and metoclopramide + fenactil treatment.

Adult↗

PubMed1993

[Survival, complications and quality of life in patients with breast cancer after ovariectomy and hormonal therapy].

Seventy one women with breast cancer in clinical stage IIIa were treated by chemotherapy and radical operation on the basis five features, namely: survivals, relapses, metastases, quality of life, and post-therapy complications. The two treatment methods were compared. The dependence between survivals and time elapsed between breast surgery and ovariectomy was evaluated. Women treated by ovariectomy suffer from; menopause symptoms, osteoporosis, blood coagulation distortions more after than women treated by hormonotherapy. Tamoxifen therapy increases the rate of breast cancer relapses and probably it is the cause of breast cancer metastases into liver. Women who underwent hormonal castration are professionally active more after them women treated by ovariectomy. Time elapsed between breast surgery and ovariectomy does not affect survivals in stage IIIa. In stage IIIb however, performing later ovariectomy prolongs survivals.

Adult↗

PubMed1991

HIV seroprevalence among childbearing women in Connecticut.

A seroprevalence survey of human immunodeficiency virus (HIV) among childbearing women in Connecticut is being conducted as one of the family of HIV seroprevalence surveys funded by the Centers for Disease Control (CDC). Between 1 April 1989 and 30 March 1990 dried blood specimens submitted from all newborns (45,890) for metabolic screening were examined for HIV antibodies by standard laboratory techniques in a blinded manner. The overall HIV prevalence rate was 0.30% (138 newborns). Rates did not differ significantly by mother's age group in the overall population. Rates of seropositivity were higher among blacks (1.2%) and Hispanics (0.69%) than among whites (0.10%). Seropositivity by town was highest in New Haven (1.6%) where one in every 63 residents who gave birth was infected. Based upon this survey, we estimate that 45 HIV-infected children were born in Connecticut during the one-year study period and that approximately 2,300 women of childbearing age are currently infected.

Adult↗

PubMed1989

Comparative studies of three serologic methods for the measurement of Mycoplasma pneumoniae antibodies.

Antibodies against Mycoplasma pneumoniae in the sera of patients and normal adult controls were measured by a standard complement fixation (CF) test, a commercial immunofluorescence (IF) test (CROWNTITRE), and a commercial enzyme-linked immunosorbent assay (ELISA) (MYCOPLASMELISA). The findings showed that, in the control sera, 269 of 277 (97%) had negative results for CF antibodies. Of the 320 controls tested by the IF assay, all (100%) had negative results for IgM antibodies and 314 (98%) had negative results for IgG antibodies. Only 6 of the 201 (3%) controls by the ELISA were classified as negative/equivocal. Among the 450 patient sera, 105 (23%) had positive results for CF antibodies, and 158 (35%) had positive results for IgG and/or IgM membrane antibodies by the IF test; 424 of these patients' sera were also tested by the ELISA, and 397 (94%) of them were found to have positive results for anti-M. pneumoniae IgG antibodies. If the CF test were chosen as the standard for comparison, the IF test would have a sensitivity of 87% and a specificity of 81% and the ELISA would have a sensitivity of 71% and a specificity of 80%, provided an adjustment in the threshold ELISA-positive value was made. A single positive M. pneumoniae membrane IgM antibody titer appeared to be valuable for a presumptive diagnosis of an ongoing infection; 41 of 47 (87%) of the IgM-positive results in the paired sera were supported by a fourfold increase or a stable high level of CF antibody titer.

Antibodies, Bacterial↗

PubMed1986

Microtiter latex agglutination--quantitative and qualitative equivalent to hemagglutination inhibition for detection of rubella antibody.

Sera were tested for rubella antibody by a standard hemagglutination inhibition method and by latex agglutination in microtiter plates (Virogen Rubella Micro Test). When 157 sera were examined by hemagglutination inhibition and by microtiter latex agglutination for immune status, 149 of the results agreed. The eight discrepant sera (all hemagglutination inhibition-negative, latex agglutination-positive) were tested by a card latex agglutination method (Rubascan) and a passive hemagglutination method (Rubacell). Results, except where noted, agreed with those of the microtiter latex agglutination. One hundred forty-eight of the 149 sera that were in agreement as to immune status were also within a fourfold variation when hemagglutination inhibition and latex agglutination titers were compared. An additional 100 sera were tested for immune status by microtiter latex agglutination and by passive hemagglutination with the single discrepant result agreeing with the latex agglutination when tested by a third method. Both microtiter latex agglutination and hemagglutination inhibition agreed in detection of fourfold or greater rises in each of 20 paired sera.

Antibodies, Viral↗

PubMed1974

[Not Available].

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Education, Medical↗