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A Borkowski

Publications and source records attributed to A Borkowski.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1996

Restoration of the continuity of dog ureter after resection of its 5 cm middle segment.

OBJECTIVE: To evaluate the restoration of the ureter of the dog after resection of a 5 cm-long middle segment. MATERIALS AND METHODS: Eight dogs underwent resection of the middle segment of the ureter, after which a 6-8 F Bard ureteric stent modelling catheter was inserted into both remaining portions of the ureter for 3 months. One month after removal of the stent the animals were killed and their ureters examined both grossly and microscopically. Paraffin-embedded sections were subjected to microscopic and immunohistochemical studies. RESULTS: The continuity of the ureter was restored but the reconstructed segment was narrowed to a variable extent. The wall of the ureter was lined by normal urothelium but consisted of fibrous connective tissue which failed to produce a regular coat. The reconstructed segment showed no smooth muscle cells (negative staining with azan and a negative reaction with monoclonal antibodies against desmin). A few smooth myocytes were found only at the border with intact portions of the ureter. CONCLUSIONS: The surgical procedure resulted in the restoration of ureteric continuity by repair and not by regeneration of its wall.

Animals↗
PubMed1996

Elevated prostate-specific antigen levels in black men and white men.

The usual ranges for prostate-specific antigen (PSA) are derived from a community-based population of White men but are used for screening on all men on the assumption that the differences between the PSA levels of different racial groups are small or have no clinical significance. Recently published reports, however, suggest that PSA levels in a specific racial population may vary directly with the relative risk of prostatic cancer within that population. PSA ranges were determined in Black and White men registered with the Veterans Affairs Maryland Health Care System, Baltimore, Maryland. The total patient census of 122,602 has near-equal numbers of Black and White men and maintains records of race designation for inpatients. Among the male patients with no known prostatic cancer, there were 10,808 men 40 years of age or older and 19,482 PSA test results. In this group, there were 3274 men identified as Black; 2993 identified as White, Not of Hispanic Origin, and 4541 identified as Other Race or Race Unknown. The 95th percentile PSA values in Black men and White men 40 through 49 years of age were 2.80 ng/mL and 2.01 ng/mL, respectively; 50 through 59 years old, 5.40 ng/mL and 4.19 ng/mL, respectively; 60 through 69 years old, 9.59 ng/mL and 7.00 ng/mL, respectively; 70 through 79 years old, 15.45 ng/mL and 9.40 ng/mL, respectively; and for men older than 80 years of age, the 95th PSA values were 21.05 ng/mL in Black men and 18.25 ng/mL in White men. In every age group, Black men had a higher range (for the 95th percentile) than did White men. The largest difference was found in men 70 through 79 years old; in this age group, the ratio of the upper limit of PSA for Black men compared with White men was 1.6 ng/mL.

Adult↗
PubMed1995

Urethral stricture as unusual complications of Wegener's granulomatosis.

A patient with Wegener's granulomatosis is reported. The diagnosis was confirmed by parotid gland biopsy. The patient responded to treatment with cyclophosphamide and prednisone. After many years, urethral stricture and subglottic stenosis developed and responded satisfactorily to surgery.

Adult↗
PubMed1995

Quantitative image analysis of p53 protein accumulation in keratoacanthomas.

Keratoacanthomas are benign skin tumors that grow rapidly but eventually regress. They occur most commonly in sun-exposed skin and are histologically remarkably similar to squamous cancers. Since mutations of the p53 tumor suppressor gene are found frequently in cutaneous squamous cell carcinomas, we hypothesized that p53 mutations might contribute to the development of keratoacanthomas. To address this question, we did p53 immunohistochemistry with a polyclonal rabbit antiserum, CM-1, that binds both mutant and wild-type p53 proteins. Although wild-type p53 protein degrades rapidly and is generally undetected by immunohistochemistry, mutant p53 protein has a longer half-life and accumulates to detectable levels. We tested 26 formalin-fixed keratoacanthomas and 4 normal skin biopsies. Positive nuclear staining was detected in 20 of 26 (77%) of the keratoacanthomas and in none of the normal skin samples. Nuclear staining occurred in the outermost layer of the neoplasms and not in the keratin-filled central cores. Since nuclear p53 protein within a cutaneous squamous cell carcinoma usually correlates with missense mutation, these data suggest that p53 mutations contribute to the development of this benign neoplasm. The histologic similarity to squamous cell carcinoma and the accumulation of p53 protein suggest progression toward malignancy, but the invariable regression of these tumors suggests an arrest at some point in multistage carcinogenesis. If this model is correct, then genetic analysis of keratoacanthomas may provide clues to the later stages of squamous carcinogenesis including local invasion and metastasis.

Animals↗
PubMed1995

Impact of unfunded research in medicine, pathology, and surgery.

The impact of unfunded medical research (ie, research conducted with no visible means of support) has received scant attention. In this study, we counted research contributions from the 10 most-cited journals in the fields of internal medicine, pathology, and surgery. Ten consecutive articles, excluding case reports and review articles, for the years 1987, 1989, and 1991 were sampled from each of 10 journals for the three areas of medicine. Unfunded articles accounted for the majority of contributions (60% of pathology articles, 62% of internal medicine articles, and 74% of surgery articles). In 1987, funded research articles published received somewhat more citations (2,961) than unfunded research articles (2,368). Among articles supported by an NIH grant, the first author of the article was seldom the grant's principal investigator (38.6%, 26.9%, and 16.7% of funded articles by pathologists, internists, and surgeons, respectively). These results indicate that unfunded research plays a major role in medical research.

Authorship↗
PubMed1995

Studies on TGF-beta 1 gene expression in the intima of the human aorta in regions with high and low probability of developing atherosclerotic lesions.

Certain regions of the human aorta are at greater risk for early and more severe atherosclerotic lesions development than others. Cornhill and coworkers (Cornhill FJ et al.: Arteriosclerosis 5:415, 1985) created maps for the probability of developing atherosclerosis defining the high-probability region (HPR) in the dorsal descending thoracic aorta and the low-probability region (LPR) in the ventral descending thoracic aorta. Our study examines the hypothesis that transforming growth factor beta -1 (TGF-beta 1), a well-known suppressor of growth and function in many human cell lines, is one of the inhibitors of human atherogenesis. The present experiment analyzes the expression of mRNA for TGF-beta 1 in both the HPR and the LPR of aortas from young (age 17 to 25 y) males of black (n = 8) and white (n = 7) race. The level of TGF-beta 1 gene expression was assessed in the aortic intima in both the HPR and the LPR, using National Institutes of Health Image 1.47, an Apple Macintosh application capable of digital image processing, analysis, and morphometric measurement. There was significantly lower (P = 0.002, alpha = 0.05) TGF-beta 1 gene expression in the HPR than in the LPR in the 22- to 25-y age group. There was no significant difference in the 17- to 21-y age group and between the HPR and the LPR in the entire study group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

p53 protein accumulates frequently in early bronchial neoplasia.

p53 mutations are common in human lung cancer and frequently generate levels of p53 protein that are detectable by immunohistochemistry. For this reason, p53 protein accumulation is a candidate biomarker, but little is known about its timing or frequency in multistage bronchial carcinogenesis. We studied human lung tissues containing preinvasive squamous neoplasms from 34 donors with and without lung cancer. Nuclear p53 protein was present in 0% of normal mucosas, 6.7% of squamous metaplasias, 29.5% of mild dysplasias, 26.9% of moderate dysplasias, 59.7% of severe dysplasias, 58.5% of carcinomas in situ, 67.5% of microinvasive carcinomas, and 79.5% of invasive tumors. These data indicate that (a) p53 protein accumulates in about 30% of the earliest recognized neoplastic lesions (i.e., mild dysplasia), (b) there is an increasing frequency of p53 protein accumulation starting with mild dysplasia, and (c) p53 protein accumulates infrequently in normal or metaplastic mucosa. In a subset of six patients whose most advanced lesion was carcinoma in situ without evidence of invasive cancer, p53 protein was detected in 0% of normal mucosas, 8.3% of squamous metaplasias, 37.5% of mild dysplasias, 12.5% of moderate dysplasias, 93.8% of severe dysplasias, and 55% of carcinoma in situ lesions. These data show clearly that p53 alterations can occur before invasion and suggest that the frequency is similar to that observed in the full series. Since two-thirds or more of lung cancers have p53 alterations, the timing and frequency of p53 protein accumulation make the p53 tumor suppressor gene an attractive marker for early diagnosis and evaluation of chemoprevention agents.

Biomarkers, Tumor↗
PubMed1993

Rapid growth of pseudoangiomatous hyperplasia of mammary stroma in axillary gynecomastia in an immunosuppressed patient.

Pseudoangiomatous hyperplasia of mammary stroma is a rare, benign mesenchymal proliferation that sometimes mimics angiosarcoma. To our knowledge, it has not been reported in men. We report the first case of this unusual entity in a man. This case was most unusual in that it occurred in a clinical setting of immunosuppression, in axillary gynecomastia, and was growing rapidly.

Adult↗
PubMed1992

[Late vesico-vaginal fistula after colporrhaphy for urinary incontinence].

We present a case of a 65 year-old woman with a late vesicovaginal fistula after colporrhaphy. Too late proper diagnosis of that complication caused perivesical tissue inflammation and led to damage to the urinary bladder, occlusion of the urethra as well as created a massive inflammatory tumor in the minor pelvis, which suggested a cancerous process. Bilateral hydronephrosis forced us to make bilateral nephrostomy. After intensive antiinflammatory therapy, anterior exenteration and Bricker's operation were performed with a finally good effect.

Aged↗
PubMed1992

Research by pathologists not funded by external grant agencies: a success story.

The paradigm of pathology research as an endeavor among grant-funded principal investigators resulting in first-author publications is unsupported by quantitative examination of author profiles extracted from the scientific literature. Publications in six pathology journals (Modern Pathology, American Journal of Surgical Pathology, Human Pathology, Acta Cytologica, Archives of Pathology and Laboratory Medicine, and American Journal of Clinical Pathology) and three general science journals (Science, New England Journal of Medicine, and Proceedings of the U.S. National Academy of Sciences) were reviewed. Twenty articles per journal from each of three years (1987, 1989, and 1991) were examined (a total of 520 articles). Of these, 295 articles were first-authored by a member of a department of pathology. Of the 295 articles first-authored by a member of a pathology department, 47 (16%) articles listed competitive grant support. Of the grant-supported articles, 20 articles listed NIH support, but only four had an NIH-supported principle investigator as the first author of the article. Unfunded research represented the vast majority (84%) of work produced by pathologists. A review of the ISI Citation Index showed that those articles written by funded pathologists averaged 8.7 (S.D. 7.8) citations per article, compared to 10.4 (S.D. 12.1) citations per article for unfunded pathologists. Results suggest that unfunded research accounts for the majority of pathology research activity as well as their resulting literature citations.

Authorship↗
PubMed1991

Spontaneous monokine release by alveolar macrophages in chronic sarcoidosis.

In pulmonary sarcoidosis an activation of alveolar T lymphocytes and alveolar macrophages (AM) has been demonstrated. There is evidence that in contrast to acute disease a heightened T-cell response cannot be observed in the chronic phase of sarcoidosis. The role of AM in the inflammatory process of chronic sarcoidosis is not yet intensively evaluated. To address this question we measured the release of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by AM of 39 patients with chronic sarcoidosis (duration greater than 4 years; 30 active, 9 inactive diseases) without therapy and correlated the monokine release with parameters of T-cell alveolitis and the course of the disease. The T4/T8 ratio was higher in the active than in the inactive group without reaching statistical significance. TNF alpha as well as IL-1 is spontaneously released by AM of the active group 2,099 +/- 518 pg/ml TNF alpha/10(6) cells/24 h and 8/13 (IL-1+/total) respectively. In the inactive group the AM release 375 +/- 246 pg/ml TNF alpha/10(6) cells/24 h which is in the range of the control and 1 out of 5 patients was IL-1-positive. There was no correlation between the monokine release and any parameter of T-cell alveolitis. These data support the hypothesis that the inflammatory process in chronic sarcoidosis is dominated by the activity of AM and that this activity determines the course of the disease.

Adult↗
PubMed1991

Estrogen-like activity of a subpopulation of natural antiestrogen receptor autoantibodies in man.

We recently reported that a subpopulation of immunoglobulin G (IgG) in man interacts with the hormone-binding site of estrogen receptors (ER), competes with [3H]estradiol (E2) uptake, and decreases effective ER concentrations in cell cultures. The present work further characterizes the immunological properties of these antibodies and defines their biological activity. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting techniques, enriched preparations of the natural anti-ER IgG subpopulation (IgGs) were found to specifically immunoprecipitate ER extracted from MCF-7 mammary carcinoma cells and to compete with [3H]tamoxifen-aziridine for ER binding. During 18-h incubations IgGs decreased [3H]E2 binding capacity of MCF-7 cells in a dose-dependent manner similar to E2. Like E2 but unlike antiestrogens, this biological effect corresponded to down-regulation of the receptor protein and depended on a mechanism specifically inhibited by actinomycin D. Moreover, IgGs antagonized the decrease of [3H]E2 binding capacity produced by the strong antiestrogen methyl-hydroxytamoxifen; this antagonism was additive to that of E2. On the other hand, IgGs like estrogens increased progesterone receptor concentrations and cathepsin D secretion. The biological activity of IgGs was neutralized by anti-IgG antibodies and by ICI 164,384, a "pure" steroid antagonist of E2, confirming that immunoglobulins G were responsible for this activity and acted at the E2-binding site. These observations indicate that some natural antibodies in man can function like potent estrogens on ER and mammary cells.

Autoantibodies↗