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Biomedical subjects

A Borkowski

Publications and source records attributed to A Borkowski.

At least 37 records · Page 2Linked to original sources
PubMed1999

Analysis of V(H)-D-J(H) gene transcripts in B cells infiltrating the salivary glands and lymph node tissues of patients with Sjögren's syndrome.

OBJECTIVE: In patients with Sjögren's syndrome (SS), B lymphocytes have been found to infiltrate salivary glands, resulting in sialadenitis and keratoconjunctivitis. The disease is frequently associated with benign and neoplastic lymphoproliferation. The present study was undertaken to investigate whether clonal B cell expansion takes place in lymphocytic infiltrations of salivary glands under (auto- [?]) antigen stimulation, by analyzing in more detail the variable part (V(H)-D-J(H)) of the immunoglobulin heavy chain genes expressed in these B cells. METHODS: Biopsies of the labial salivary glands and lymph nodes were performed on 2 female patients with SS. The Ig gene rearrangements in these tissues were amplified by reverse transcriptase-polymerase chain reaction using specific primers. RESULTS: A total of 94 V(H)-D-J(H) transcripts were cloned and sequenced. Our data suggest a polyclonal origin of the B cell infiltrates. In 92 of the transcripts, V(H) genes were modified by somatic mutation. Further analysis showed counterselection for replacement mutations within the framework regions, suggesting that those B cells were stimulated and selected for functional expression of a surface Ig. In labial salivary glands from both patients, clonally related B cells became evident. Members of 1 particular clone were found in both the lip and lymph node material. CONCLUSION: These data provide evidence, on the nucleotide sequence level, that an antigen-triggered clonal B cell expansion takes place in the salivary glands of patients with SS who do not have histologic evidence of developing lymphoma. It may be speculated that those B cell clones expand during disease progression, resulting in lymphomagenesis.

Amino Acid Sequence↗
PubMed1999

Loss of cell cycle regulators p27(Kip1) and cyclin E in transitional cell carcinoma of the bladder correlates with tumor grade and patient survival.

The cyclin-dependent kinase inhibitor p27(Kip1) is a powerful molecular determinant of cell cycle progression. Loss of expression of p27(Kip1) has been shown to be predictive of disease progression in several human malignancies. In this study we investigated the expression of two key cell cycle regulators, p27(Kip1) and cyclin E, in the progression of transitional cell carcinoma of the bladder. An immunohistochemical analysis was conducted in a series of 50 bladder tumor specimens, including 3 metastatic lymph nodes, and 7 normal bladder specimens, using specific antibodies against the two regulators of the cell cycle, p27(Kip1) and cyclin E. The degree of immunoreactivity was correlated with the pathological tumor grade, stage, and patient survival. A uniformly intense immunoreactivity for p27(Kip1) and cyclin E was observed in epithelial cells of normal bladder tissue. Malignant bladder tissue demonstrated a heterogeneous pattern of significantly reduced p27(Kip1) and cyclin E immunoreactivity, compared with normal urothelium (P < 0.01). In addition, there was progressive loss of expression of both cell cycle proteins with increasing tumor grade and pathological stage. Expression of p27(Kip1) was significantly lower in the poorly differentiated tumors (grades III) compared to well and moderately differentiated (grades I and II) tumors (P = 0.004). Moreover, the expression of cyclin E was lower in grade III tumors compared to grade I and II lesions, although this difference failed to reach statistical significance. Most significantly, Kaplan-Meier plots of patient survival show increased mortality risk associated with low levels of p27(Kip1) (P = 0.001) and cyclin E (P = 0.002) expression. This is the first evidence that loss of expression of p27(Kip1) and cyclin E in human bladder transitional cell carcinoma cells correlates with advancing histological aggressiveness and poor patient survival. These results have clinical importance, because they support a role for p27(Kip1) and cyclin E as novel predictive markers of the biological potential of bladder tumors that will enable identification of those tumors most likely to progress to muscle invasive disease and of patient survival.

Adult↗
PubMed1999

Color duplex ultrasonography in large-vessel giant cell arteritis.

In a patient with active extracranial giant cell arteritis, duplex ultrasonography demonstrated hypoechoic mural thickening of the brachial, axillary, subclavian, and carotid arteries with bilateral subtotal occlusions of the brachial and axillary arteries. The ultrasound image of the artery walls became midechoic within 8 weeks, and hyperechoic within one year after start of treatment with corticosteroids. A similar hypoechoic mural thickening of the temporal arteries has been recently described in active giant cell arteritis. The dark ultrasound image is due to an edema of the vessel wall in the acute stage. The brighter ultrasound image might be due to fibrosis in the chronic stage of the disease.

Blood Flow Velocity↗
PubMed1999

Prepregnancy testing for single-gene disorders by polar body analysis.

Preventive measures for single-gene disorders are currently based on carrier screening in pregnancy and prenatal diagnosis. Although this has been extremely effective for preventing new cases of common inherited conditions, the major limitation is still termination of 25% of wanted pregnancies following detection of affected fetuses. To overcome this important problem, we developed a method for prepregnancy genetic testing that involves DNA analysis of the first and second polar bodies, which are extruded during maturation and fertilization of oocytes. We offered this option to 28 couples at risk for having children with single-gene disorders. Fifty clinical cycles were performed from these patients for the following conditions: 20 for cystic fibrosis, 18 for thalassemia, 6 for sickle cell disease, 2 each for Gaucher disease and LCHAD (long-chain 3-hydroxyacyl-COA dehydrogenase deficiency), and 1 each for hemophilia B and phenylketonuria. Oocytes obtained from these patients using in vitro fertilization procedures (IVF) were tested by a sequential multiplex nested PCR analysis of the first and second polar body to detect the gene involved simultaneously with linked polymorphic markers. A total of 191 of 399 oocytes with predicted genotype were mutation free and preselected for fertilization and transfer. In all but three cycles, one to three unaffected embryos with predicted unaffected genotypes were transferred, resulting in 20 pregnancies, from which 19 healthy children have been born. The follow-up analysis of embryos resulting from oocytes with predicted affected genotype, confirmed the diagnosis in 97% of cases, demonstrating the reliability of prepregnancy diagnosis of single-gene defects by polar body analysis.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1999

Alpha 1-adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia.

PURPOSE: Recent evidence indicated that an alpha 1 blocker, doxazosin, induces prostate apoptosis in patients with benign prostatic hyperplasia (BPH). In this study, to determine whether this apoptotic response was mediated by alpha 1 adrenoceptor-dependent mechanism or was specific to doxazosin, we examined the effect of another alpha 1 blocker, terazosin, in addition to doxazosin, on the dynamics of prostate cell growth. MATERIALS AND METHODS: Cell proliferation and apoptosis were evaluated in BPH patients, an untreated (control) group (n = 31), and men treated with terazosin (n = 42) and doxazosin (n = 61) for the relief of the obstructive symptoms. Terazosin (1 to 10 mg./day) and doxazosin (2 to 8 mg./day) treatment varied from 1 week to 3 years. Ki-67 immunostaining and the TUNEL assay were used to evaluate the proliferative and apoptotic indices, respectively, in both the epithelial and stromal components of prostate (biopsy and prostatectomy) specimens. The smooth muscle cell content of the prostatic stroma was identified on the basis of smooth muscle alpha-actin immunoreactivity. RESULTS: A significant induction of apoptosis was observed in both the prostatic epithelial and stromal cells within the first month of terazosin and doxazosin therapy, as compared with untreated controls (p < 0.05). Furthermore, the marked induction of prostatic stroma apoptosis in response to both alpha 1 adrenoceptor antagonists was paralleled by a significant decrease in the smooth muscle alpha-actin expression. This loss of prostatic smooth muscle cells correlated with morphological stromal regression (as detected by trichrome staining) and BPH symptom improvement. Neither terazosin nor doxazosin therapy resulted in significant changes in prostate cell proliferation. CONCLUSIONS: These findings demonstrate that alpha-blockers as a class may regulate prostate growth by inducing apoptosis in both the epithelial and stromal cells, with little effect on cell proliferation. Apoptosis-mediated prostate stromal regression appears as a molecular mechanism underlying the therapeutic response to alpha 1 blockade in the treatment of BPH.

Adrenergic alpha-Antagonists↗
PubMed1998

Review of recent placebo-controlled trials utilizing phytotherapeutic agents for treatment of BPH.

BACKGROUND: In order to assess the efficacy of phytotherapeutic agents for the treatment of benign prostatic hyperplasia (BPH), a review of recently published double-blind placebo-controlled trials was undertaken. METHODS: Only those studies reviewed by the Other Medical Therapies Committee of the Fourth International Consultation on BPH were included. RESULTS: These studies suggest a possible benefit for the use of phytotherapeutic preparations in the treatment of BPH. CONCLUSIONS: These studies need to be confirmed in larger long-term placebo-controlled studies in order to ascertain the true efficacy of these agents.

Anti-Bacterial Agents↗
PubMed1998

Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia.

PURPOSE: The molecular mechanisms underlying the therapeutic effect of the alpha1 blocker, doxazosin, on benign prostatic hyperplasia (BPH) are poorly understood. We evaluated the effect of doxazosin on cell proliferation and apoptosis in the prostatic glandular epithelium and stroma of patients with BPH. MATERIALS AND METHODS: We examined proliferative and apoptotic activities in prostate specimens of 22 men a mean of 65 years old with BPH before and after doxazosin treatment within the normal therapeutic range. Proliferative and apoptotic indexes were determined using Ki-67 nuclear antigen staining and the terminal transferase end labeling assay, respectively. The smooth muscle cell content in prostatic specimens was identified by smooth muscle alpha-actin, and desmin immunoreactivity and apoptotic indexes were correlated with prostatic stromal tissue regression and improvement in BPH symptoms. RESULTS: In response to doxazosin treatment there were no significant changes in the kinetics of cell proliferation in the prostatic epithelial or stromal cell population. Mean pretreatment baseline apoptosis was 1.9 and 1.0% for the epithelial and stromal prostate components, respectively. Mean apoptotic indexes significantly increased after 3 months of doxazosin treatment in the glandular epithelial (6%) and smooth muscle cells (15%). By 12 months after treatment epithelial apoptosis had decreased to constitutive levels, while the apoptotic index of prostatic stroma cells remained high. Doxazosin induced smooth muscle cell apoptosis correlated with prostatic stromal degeneration, decreased alpha-smooth muscle actin expression and improved BPH symptoms. CONCLUSIONS: These findings implicate the induction of prostate apoptosis by doxazosin as a potential molecular mechanism underlying the acute and chronic therapeutic responses of BPH to alpha1 blockade.

Adrenergic alpha-Antagonists↗
PubMed1998

bcl-2/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with prostate cancer.

OBJECTIVES: Markers predictive of therapeutic response of prostatic tumors to radiotherapy may have major significance in optimizing effective treatment of prostate cancer. Because inherent cellular radioresistance plays a critical role in the failure of radiotherapy, in this study, we investigated whether there is a correlation between the ratio of two apoptosis regulators, bcl-2 (apoptosis suppressor) and bax (apoptosis inducer) in prostatic tumors and the clinical response to radiotherapy in patients with localized prostate cancer. METHODS: A retrospective review of records of 41 patients who underwent external beam radiotherapy for prostate cancer was conducted. On the basis of post-treatment prostate biopsy and prostate-specific antigen (PSA) criteria, the cancers of 20 patients were classified as radiation nonresponders and 21 as radiation responders. Immunohistochemical analysis was performed on paraffin-embedded prostate sections to determine the level of expression of the two apoptotic proteins, bcl-2 and bax, in tumor cells. RESULTS: bcl-2 immunoreactivity was significantly higher in prostatic tumors not responsive to radiotherapy (38.6+/-4.1), compared with the radiation responders (24.1+/-4.6) (P <0.001). Expression of bax protein was lower in nonresponders, but values were not significantly different from the responders. The resulting significantly higher bcl-2/bax ratio (P <0.01) correlated with poor therapeutic responsiveness of prostate cancer to radiotherapy (1.12+/-0.12 and 0.56+/-0.13, for nonresponders and responders, respectively). This correlation (r=0.67) was independent of age, PSA, and Gleason score. CONCLUSIONS: These findings suggest that patients with an elevated bcl-2/bax ratio are at increased risk of their cancer failing to respond to radiotherapy. This study suggests a predictive value for the bcl-2/bax ratio as a potential molecular marker for predicting radioresistance of prostatic tumors.

Aged↗
PubMed1998

Long-term subjective results of Marshall-Marchetti-Krantz procedure.

OBJECTIVE: Retrospective, subjective evaluation of results of suprapubic vesicourethropexy (Marshall-Marchetti-Krantz procedure) for stress urinary incontinence. MATERIAL: A total number of 81 patient records operated between 1980 and 1994 at our institution were reviewed and questionnaires were mailed to them to estimate the success rate, period of continence, current complaints and patient satisfaction. Patients with primary incontinence constituted 73% of this group, the remainder of 27% being recurrent or persistent incontinence. RESULTS: The response rate was 75% (60 cases) and this group was evaluated. Mean postoperative time was 9.9 (2-15) years at the time of assessment. Mean duration of continence was 78.5 months and was not influenced by prior hysterectomy or parity. Weak correlation was found between patients' age and continence period. It was similar in patients operated in their 5th and 6th decades of life and was shorter in the 7th decade. Additional sutures placed between the anterior bladder wall and rectus fascia (Lapides modification) resulted in a longer continence period. Cure rates decreased with time and were 81, 77, 57 and 28% after 6, 12, 60 and 120 months respectively. In the incontinent group, 34% of patients described leakage degree as lesser than preoperatively and 65% required protection. As many as 90% of continent and 62% of incontinent women evaluated their urinary system status as better than preoperatively. 90% of continent and 69% of incontinent women would repeat surgery again. CONCLUSIONS: This procedure is characterized by a high 81% early postoperative success rate that decreases with time. Despite recurrence of stress incontinence, one third of patients declare lesser incontinence degree and do not require protection.

Adult↗
PubMed1998

p21waf1/cip1 and transforming growth factor beta 1 protein expression correlate with survival in non-small cell lung cancer.

p21waf1/cip1 encodes a cyclin-dependent kinase inhibitor that is transcriptionally activated by the p53 tumor suppressor gene, transforming growth factor beta 1 (TGF-beta 1), AP2, and other pathways. Because p21waf1/cip1, p53, and TGF-beta 1 all regulate apoptosis and the cell cycle, we tested the hypothesis that their relative protein levels would correlate with biological features including the survival of non-small cell lung cancer (NSCLC) patients. We conducted an immunohistochemical analysis of p21waf1/cip1 and TGF-beta 1 and identified four patient groups with distinct survival outcomes. Concordant p21waf1/cip1 and TGF-beta 1 expression (i.e., either high p21waf1/cip1 and high TGF-beta 1 expression or low p21waf1/cip1 and low TGF-beta 1 expression) predicted 70% disease-free survival at 2000 days of follow-up. Discordant p21waf1/cip1 and TGF-beta 1 expression (i.e., either high p21waf1/cip1 and low TGF-beta 1 expression or low p21waf1/cip1 and high TGF-beta 1 expression) predicted 35% disease-free survival (P = 0.0003; log-rank test). These survival relationships were not attributable to differences in grade, stage, or p53 status. Although current models do not fully explain these complex interactions, most of these data fit a paradigm whereby TGF-beta 1 regulation determines NSCLC survival. In addition to the survival correlation, we found that high p21waf1/cip1 protein expression correlated with high tumor grade (P = 0.014). There is little evidence that p21waf1/cip1 protein levels accurately predict p53 mutation status in NSCLC; specifically, 20 of 48 (42%) tumors with p53 mutations contained high levels of p21waf1/cip1 protein. These findings indicate that p21waf1/cip1 immunohistochemical analysis may provide useful information concerning the biological properties of NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Integrity of p53 in hepatitis B x antigen-positive and -negative hepatocellular carcinomas.

Inactivation of the tumor suppressor p53 seems to be important to the pathogenesis of hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus infection. Although this inactivation may be due to mutations in the p53 gene, recent evidence suggests that the hepatitis B virus-encoded X antigen (HBxAg) binds to and inactivates wild-type p53. Hence, experiments were designed to test the hypothesis that there is a low frequency of p53 mutations in HBxAg-positive HCC. HBxAg and p53 were assayed by immunohistochemistry (IHC) in HCC and nontumor liver from 16 Chinese patients, half of whom were hepatitis B surface antigen carriers. HBxAg was detectable in tumor and/or nontumor cells from all patients by IHC; six of these samples also had detectable p53. To determine whether p53 detection by IHC, and hence stabilization, is associated with mutation, sequencing of p53 exons 5-8 was performed with each patient sample. Wild-type sequences were found in 13 of 16 HBxAg-positive cases (81%). Hence, HBxAg is a common marker of HCC that correlates with the persistence of wild-type p53 among both carriers and noncarriers. The low frequency of p53 mutations in HCC in these patients implies that p53 inactivation may occur predominantly by complex formation with HBxAg.

Carcinoma, Hepatocellular↗
PubMed1997

Natural antiestrogen receptor autoantibodies in man with estrogenic activity in mammary carcinoma cell culture: study of their mechanism of action; evidence for involvement of estrogen-like epitopes.

We previously reported that human natural autoantibodies enriched in antiestrogen receptor Ig (IgGs) display estrogenic activity in MCF-7 mammary carcinoma cells. In this study, we investigated IgGs' mechanism of action. We showed that: 1) IgGs Fab fragments (which contain only one antigen binding site) induced an estrogenic response in MCF-7 cells, producing estrogen receptor (ER) down-regulation and an increase in progesterone receptor concentration; 2) IgGs specifically inhibited MCF-7 cell surface labeling with fluorescent estradiol (E2)-BSA conjugates; 3) this inhibition of E2-BSA binding to membrane estrogen binding sites was largely caused by natural anti-E2-BSA antibodies (Ab) selectively associated with the natural anti-ER Ab within IgGs; 4) furthermore, these natural anti-E2-BSA Ab accounted for most of IgGs estrogenic activity in cell culture; 5) however, when incubated with cytosolic ER, they did not behave like estrogens, but they decreased ER hormone binding capacity; and 6) although IgGs stimulated cAMP production, their anti-E2-BSA Ab subpopulation did not. In conclusion, the estrogenic activity of IgGs does not involve Ab mimicking E2 molecular configuration or ligand-independent cAMP mediated pathways, membrane Fc receptors, and membrane receptor cross-linking mechanisms. On the contrary, IgGs seem to function by neutralizing estrogen-like epitopes, associated with ER-related peptides, which might inhibit ER activation.

Animals↗
PubMed1997

[Diagnosis and treatment of vesicouterine fistula occurring after cesarean section].

Eleven cases of vesicouterine fistula were reported. The initial diagnosis was made when urinary incontinence was occurring. The diagnosis was best confirmed by cystoscopy and hysterography, which was positive in 9 cases. The ultrasonographic examinations allow to visualize the fistula in 5 out of 6 cases examined and to establish the diagnosis. If sonographic examination visualizes the fistula, the performing of hysterography is not necessary. The management consists of the cure of the infection of the urogenital tract and abdominal operation based on the excision of the fistula and closing of the bladder and uterus. All operated patients were cured.

Adult↗
PubMed1997

[Urinary diversion to the large intestine in adults].

The paper presents the history of technique and concepts of urinary diversion to colon and rectum from the mid-XIXth century until today, including the contribution of Polish surgeons--Kryński, Laskownicki and Kiełkiewicz. Contraindications and complications of this type of definitive urinary diversion is briefly discussed. Authors also present the outcome of ureterosigmoidostomy performed according to method proposed by Goodwin in 25 patients cystectomized for infiltrating transitional cell carcinoma of the bladder, who were operated on at the Department of Urology, Medical School in Warsaw. These patients were in poor general condition and short life expectancy, which depended upon tumour stage and grade as well as preoperative urographic evaluation of urinary tract.

Adult↗
PubMed1997

Loss of the cyclin-dependent kinase inhibitor p27(Kip1) protein in human prostate cancer correlates with tumor grade.

Loss of expression or mutational deletion of the cyclin-dependent kinase inhibitor p27(Kip1) has recently been implicated in malignant development. In this study, we investigated the relationship between p27(Kip1) protein expression and tumor grade in human prostate cancer by conducting an immunohistochemical analysis in a series of normal prostate, benign prostatic hyperplasia, and malignant prostate cancer specimens. The proliferative activity of prostatic tumors was determined on the basis of the Ki-67 nuclear antigen staining. A uniformly intense immunoreactivity for p27(Kip1) was localized to the nuclei of glandular epithelial cells of normal prostates. The benign glandular epithelia exhibited moderate immunostaining. In the malignant prostate tissue, however, a heterogeneous pattern of substantially reduced p27(Kip1) immunoreactivity was found among the glandular epithelial cells. The majority of primary prostate cancer specimens (68%) were totally negative for p27(Kip1) immunoreactivity, whereas the rest exhibited a significantly decreased p27(Kip1) expression, compared with the normal prostate (P < 0.01). Moreover, there was progressively diminished p27(Kip1) immunostaining with increased tumor grade. This loss of p27(Kip1) was associated with an increase in the proliferative index of prostatic tumors (r = 0.88). There was no significant relationship between p27(Kip) loss and the transforming growth factor beta receptor status of prostatic adenocarcinomas. These results indicate that frequent loss of the cyclin-dependent kinase inhibitor p27(Kip1) in human prostate cancer cells correlates with advancing histological aggressiveness, implicating deregulation of p27(Kip1) in prostate tumor progression.

Adenocarcinoma↗
PubMed1996

Incidence of apoptosis and cell proliferation in prostate cancer: relationship with TGF-beta1 and bcl-2 expression.

The incidence of programmed cell death (apoptosis) and cell proliferation was investigated in the normal and malignant human prostate to define the significance of their potential deregulation in human prostate cancer. The incidence of "spontaneous" apoptosis was analyzed using an in situ end-labeling procedure for detection of nucleosomal DNA fragmentation, as well as the pattern and topological localization of expression of the 2 proteins regulating apoptosis, TGF-beta1, and bcl-2, in 40 primary prostatic adenocarcinomas with varying tumor grades, 17 lymph nodes positive for metastatic prostate cancer and 9 normal prostate specimens. The basal level of cell proliferation of the different prostatic cell populations in the same specimens was determined, utilizing the Ki-67 nuclear antigen. Localized prostate cancer cells exhibited a relatively low rate of apoptosis, which was significantly lower than the apoptotic index of normal prostate glandular epithelial cells. Metastatic prostate tumor cells, however, exhibited a significantly higher apoptotic index compared with localized prostate cancer cells. A significant increase in the proliferative index was detected in prostatic tumors compared with the normal gland (5-fold), and there was an even more marked elevation in the proliferative index of the metastatic prostate tumor cells compared to the normal prostate epithelial cells (approximately 24-fold). Immunohistochemical analysis of normal and malignant prostate specimens revealed a predominant TGF-beta immunoreactivity in the glandular epithelial cells, while the stromal component was totally negative. There was a significant increase in the levels of TGF-beta in primary prostatic tumors compared to the normal prostate. Bcl-2 expression was detected among certain populations of tumor epithelial cells in a mutually exclusive topological distribution pattern for apoptosis. In marked contrast, neither TGF-beta1 nor bcl-2 immunoreactivity was detected in metastatic prostate tumor cells, despite their high proliferative and apoptotic rates. Balancing the prostatic growth equation for the prostatic tumor epithelial cell populations revealed a substantial net increase in cell number in both primary and metastatic prostate cancers. This loss of apoptotic control in favor of cell proliferation may be responsible for prostate cancer initiation and progression.

Adenocarcinoma↗