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Biomedical subjects

J Tomaszewski

Publications and source records attributed to J Tomaszewski.

At least 19 recordsLinked to original sources

Prevention of diabetic nephropathy in db/db mice with glycated albumin antagonists. A novel treatment strategy.

Accelerated protein glycation in diabetes has been mechanistically linked to the pathogenesis of diabetic nephropathy. Because glycated albumin induces abnormalities in cultured mesangial cells that resemble those characterizing the glomerular mesangium in diabetes, and monoclonal antibodies (A717) specific for Amadori-modified glycated albumin prevent these abnormalities, we postulated that in vivo administration of A717 could retard the progression of diabetic nephropathy. To test this hypothesis, diabetic db/db mice and their nondiabetic db/m littermates were treated with eight consecutive weekly injections of 150 micrograms of A717 (Fab fragments) to reduce the elevated plasma glycated albumin concentration, or with irrelevant murine IgG (MIg). Relative to nondiabetics, diabetic mice (MIg treated) manifested proteinuria (3.35 +/- 0.15 vs 0.87 +/- 0.1 mg albumin/mg creatinine), 3.8-fold increase in mesangial matrix fraction, and renal cortical overexpression of mRNAs encoding alpha 1(IV) collagen (2.6-fold increase) and fibronectin (3.8-fold increase). Treatment of db/db mice with A717 significantly reduced the proteinuria (1.52 +/- 0.3 mg/mg creatinine), inhibited mesangial matrix expansion, and attenuated overexpression of matrix mRNAs. The nephropathic protective effects of A717 were independent of any change in blood glucose concentrations. Antibodies unreactive with glycated albumin did not duplicate the beneficial effects of A717. Thus, abrogating the biologic effects of increased glycated albumin with A717 has a salutary influence on the pathogenesis of diabetic nephropathy and has novel therapeutic potential in its management.

Albuminuria

A multivariable analysis of clinical factors predicting for pathological features associated with local failure after radical prostatectomy for prostate cancer.

PURPOSE: A multivariate analysis is used to determine the predictive value of pretreatment clinical indicators on pathologic features associated with local failure after radical prostatectomy in patients with prostate cancer. METHODS AND MATERIALS: A retrospective review of the pathologic findings of 235 patients with adenocarcinoma of the prostate treated between 1990 and 1993 with a radical retropubic prostatectomy was performed. The preoperative clinical data including the serum prostate specific antigen, clinical stage, Gleason sum, and endorectal magnetic resonance scan findings are used to identify patients prior to definitive treatment who would be at high risk for having pathologic features associated with local failure at radical prostatectomy. Outcome prediction curves are constructed from a logistic regression multivariate analysis displaying the probability of pathologic involvement of the seminal vesicle, extracapsular disease, or positive surgical margins as a function of the preoperative prostate specific antigen and Gleason sum for the cases when the endorectal magnetic resonance scan is positive, negative, or not included in the multivariate analysis. RESULTS: Factors identified on multivariate analysis as significant predictors of seminal vesicle invasion include endorectal magnetic resonance scan findings (p < 0.0001), and preoperative prostate specific antigen (p = 0.017). Endorectal magnetic resonance scan findings (p = 0.0016), preoperative prostate specific antigen (p = 0.0002), and Gleason sum (p < 0.0001) were significant predictors of extracapsular extension and preoperative prostate specific antigen (p < 0.0001) and Gleason sum (p = 0.03) were significant predictors of disease extending to the margins of resection. Clinical stage was not a significant predictor (p > 0.05) of pathologic features associated with local failure on multivariate analysis. As a single modality, endorectal surface coil magnetic resonance imaging was accurate 93%, 69%, and 72% of the time for predicting seminal vesicle invasion, transcapsular disease, and final pathologic stage, respectively. Failure to recognize microscopic penetration of the capsule found at the time of pathologic evaluation in a prostate gland with a grossly intact capsule accounts for the majority (70%) of the staging inaccuracies. CONCLUSIONS: The use of the endorectal surface coil magnetic resonance scan findings in conjunction with both the serum prostate specific antigen and Gleason sum improves the clinical accuracy of predicting those patients at high risk for clinically unsuspected extraprostatic disease. In particular, for the subgroup of patients with moderately elevated prostate specific antigen (> 10-20 ng/mL) and intermediate grade clinically organ confined prostate cancer [Gleason sum: 5-7] where the specificity of these tests to predict for occult extraprostatic disease is suboptimal, the additional information obtained from the endorectal coil magnetic resonance scan allows the physician to definitively subgroup these patients into low and high risk for seminal vesicle invasion or transcapsular disease.

Adenocarcinoma

A profile of symptomatic patients with silicone breast implants: a Sjögrens-like syndrome.

Exposure of breast tissue to silicone has been associated with autoimmune diseases in the medical literature since the 1960's. Japanese women injected with raw silicone had features of a collagen vascular disease but did not meet criteria for a specific diagnosis. Subsequently, we have seen women with silicone breast implants that have similar problems. We performed a prospective noncontrolled study on women with silicone breast implants. Results from the first 50 consecutive women revealed the most prominent complaints in this group were fatigue (89%), generalized stiffness (75%), poor sleep (71%), and arthralgias (78%). Other problems included Raynaud's phenomenon, alopecia, adenopathy, night sweats, and frequent sore throats. Unexpectedly, half of these women complained of dry eyes and dry mouths. Positive antinuclear antibodies and or rheumatoid factors were discovered in 38% of patients although the anti-SSA antibody was found in only one patient and anti-SSB in none. Labial salivary gland biopsies in 5 cases showed mononuclear cell infiltrates compatible with Sjögren's syndrome in 4. The infiltrating cells were predominantly CD68 positive monocyte/macrophages, which is different from what is found in Sjögren's syndrome. These findings may indicate the presence of a unique syndrome associated with silicone implants that is characterized by musculoskeletal pain and autoimmune features.

Adult

[Synthesis of estradiol by endometrial stroma cells under the influence of epidermal growth factor (EGF) in vitro].

The endometrial samples were obtained from 13 operated women in the proliferative phase of menstrual cycle. The tissue culture of endometrial stromal cells was established. After the cells were growth to the confluency, EGF was added to dishes of study group to the final concentrations of 5 ng/ml. Culture media of study and control groups were collected every 48, 96, 144, 192 hours and lyophylized. The estradiol level was measured in culture media by RIA. The mean estradiol concentrations in culture media of endometrial stromal cells decreased during the time of experiment in the control: 318 pg/ml, 276 pg/ml, 186 pg/ml and 110 pg/ml and study group respectively: 339 pg/ml, 279 pg/ml, 169 pg/ml and 129 pg/ml. There was no significant influence of EGF (5 ng/ml) on estradiol level in culture media in each time intervals.

Cells, Cultured

[Hypomodified phenylalanine transfer RNAs (tRNA(Phe)) in uterine myoma tissue of women].

Phenol extracted crude tRNA samples obtained from uterine myoma tissue were additionally purified on DEAE-cellulose column and were finally fractionated on BD-cellulose column. Fractions eluted by ethanol gradient (concentration from 0% to 20%) were hybridized by dot blot technique with DNA probe which consisted of 15 nucleotides fragment complementary to 3' end of the tRNA(Phe). Five separate distinct peaks were found. According to genetic code rules restricted to two the number of tRNA(Phe) isoacceptors, it is assumed that three major peaks representing roughly 70% of total tRNA(Phe) pool, probably are hypomodified.

Chromatography, DEAE-Cellulose

[Fertility after adnexal surgery].

Among 64 women undergoing tubal-ovarian surgery 40.6% became pregnant spontaneously. Because of 47% of the remainder patients demonstrated anovulation the induction of ovulation was performed except the cases with hypergonadotrophic hypogonadism (9.4%). After treatment the total population with ovulatory cycles increased to 73.4% and pregnancy ratio upwards 48%. The pregnancy was noted in the half of the patients with endometriosis and all multiparas and after ectopic pregnancy.

Adult

[Angioplasty of the ostium of the left coronary artery using a venous patch].

Isolated critical ostial stenosis of the left main coronary artery (LMCA) without narrowing in the distal parts of coronary vessels is rather rare cause of angina. It was observed in 7 our patients: 5F and 2M aged 42-55 yrs (mean 47.5). Five of them were in unstable condition. In all of them a direct surgical angioplasty of the LMCA was performed. Cardiopulmonary bypass with moderate hypothermia were used in all patients. The LMCA was approached from behind. A curved incision was made into the right lateral aortic wall toward the LMCA. Care was taken to stay away from the commissure between the noncoronary and the left coronary cusp. The posterior aspect of the LMCA was incised across the stenosis and prolonged through bifurcation. A venous onlay patch was used to enlarge not only the LMCA but also the adjacent 2 cm of aortic incision, so as to give the LMCA ostium a funnel shape, which favors a homogeneous blood flow. The mean aortic cross clamping time was 46 min. The patients were easily weaned from cardiopulmonary bypass. The early and late results are good--all patients were discharged from the hospital free of symptoms. In 6 patients a perfect patency of the left main stem was documented during control coronarography. In our opinion direct surgical angioplasty of LMCA is better then the conventional surgical treatment because normal geometry of LMCA ostium and normal blood flow can be restored using this method.

Adult

[Serum ceruloplasmin activity in patients with cancer of the larynx].

The ceruloplasmin activity of serum was measured in 50 patients with larynx cancer and 50 healthy subjects. The determination of serum ceruloplasmin based on the diamine oxidase activity with o-dianisidine as a substrate. In patients with laryngeal cancer the ceruloplasmin activity was significantly higher than that in healthy controls. The increase in the ceruloplasmin activity was correlated with clinical stage of larynx cancer.

Adult

Prostate cancer: local staging with endorectal surface coil MR imaging.

Endorectal surface coil magnetic resonance (MR) imaging was used to stage the local extent of prostate cancer in 22 patients. The endorectal coil images were acquired with a 10-12-cm field of view and a 4-mm section thickness. All pathologic specimens were reviewed by one pathologist. Endorectal surface coil MR imaging was 82% accurate in the differentiation of stage B from stage C cancer. One case was overestimated, and three cases were underestimated. The three underestimated cases consisted of two cases of microscopic capsular invasion and one case of minimal seminal vesicle invasion. In a comparison of retrospective, blinded readings of endorectal coil and body coil images, there was an average improvement in accuracy of 16% in staging prostate cancer with endorectal coil images.

Carcinoma

[Changes in the levels of total and protein-bound hydroxyproline in the serum and urine of patients with cancer of the larynx after radiotherapy].

The serum concentration of total and protein-bound hydroxyproline as well as urinary hydroxyproline excretion were measured in 52 laryngeal cancer patients before, during and after irradiation. The modified colorimetric method described by Prockop and Udenfriend was used. After irradiation the increased total hydroxyproline concentration and excretion were observed, whereas no changes in serum protein-bound hydroxyproline were stated. Any correlation between the results of therapy and serum/urinary hydroxyproline levels were observed.

Adult

The effect of islet cell culture in vitro at 24 degrees C on graft survival and MHC antigen expression.

A period of in vitro culture prior to transplantation has been shown to prolong the survival of many types of MHC-incompatible endocrine grafts. The effectiveness of this strategy has been attributed to a selective depletion of intragraft antigen-presenting cells. We report that in vitro culture at 24 degrees C results in a significantly better survival of rat isolated islet allografts than does culture at 37 degrees C. Using in vitro assays of APC activity, we were unable to detect differences in the quantity of residual intraislet APCs between 24 degrees C and 37 degrees C culture preparations. In contrast, islet endocrine cells cultured at 24 degrees C evidenced a reduced level of cell surface class I MHC antigen expression and were significantly less vulnerable to lysis in vitro by CTL. These findings suggest that culture at 24 degrees C produces islet alterations other than APC depletion, and that its beneficial effect on graft survival correlates with a reduction in endocrine cell class I MHC antigen expression.

Animals

[Risk factors of coronary artery disease in males during a 3 year follow up based on a cohort study in a selected region of Lublin].

To assess changes in risk factors of coronary artery disease, examinations which had been performed in 1981 and 1982 were repeated in males aged 40-59, inhabitants of the district "Czechów" in Lublin. The study was based on Polish Experiment of Coronary Disease Multifactor Prevention assumptions 112 of 203 males investigated in 1981, 1982 underwent repeated examination (attendance rate - 55%). Statistical analysis was performed only in twice examined subjects. Significant increase of blood pressure, body weight, total serum cholesterol and uric acid concentration was stated in comparison with their respective initial values. Significant decrease of HDL-cholesterol and no changes in serum triglycerides concentration were observed. The only positive stated alteration was a lower percentage of tobacco smokers. Diagnosis of coronary artery disease remained unchanged despite of increased risk factors levels (increase of mean Rose's index score from 5 in initial examination to 6.5 in a control one). This high increase in risk factors occurrence allows an unfavourable prognosis for future incidence of coronary artery disease and also demands to undertake vigorous prevention.

Adult

De novo membranous glomerulonephropathy in renal allografts: a report of ten cases and review of the literature.

De novo posttransplantation membranous glomerulonephropathy (MGN) is the most common form of de novo glomerulopathy in renal allografts. The clinical and pathological features of ten patients with de novo MGN were studied and the related literature was reviewed to assess the clinical features, morphologic characteristics, and natural course of this disease. De novo MGN may occur in both living related and cadaveric allografts at any time after transplantation. It presents clinically either as asymptomatic proteinuria or the nephrotic syndrome, a feature of poor prognostic implication. Morphologically, de novo MGN in most instances has distinct differences from idiopathic MGN in native kidneys and is accompanied by varying features of rejection. About 50% of grafts which develop de novo MGN eventually fail. This rather poor outcome may not represent the natural history of de novo MGN per se but rather the consequences of associated chronic rejection. Evidence is presented that many of the cases of so-called de novo MGN may be a complication of transplant glomerulopathy rather than being caused by mechanisms totally independent from rejection.

Cadaver

[Prevalence of coronary disease risk factors in the male population 40-59 years of age from the housing complex "Czechów" in Lublin].

There was studied randomly selected approximately 10% sample of population of males aged 40-59 from the housing estate "Czechów" in Lublin. Authors assessed the level of coronary artery disease (CAD) basic risk factors as well as a percentage of persons with a high risk of developing CAD. The study was extended by determinations of plasma HDL--cholesterol, glucose and uric acid concentrations. Mean total cholesterol concentration (220.4 mg/dl) as well as the frequency of hipercholesterolemia occurrence (15.4%) were significantly higher in comparison with their values in male populations of Warsaw and Southern Poland. Mean systolic (134.2 mm Hg) and diastolic (87 mm Hg) blood pressures as well as frequency of hypertension occurrence (22.7%) were comparable with results of two, above mentioned, epidemiological studies. We stated the lower percentage of current tobacco smokers (52.2%). The overweight of 115% or more was stated in 22.2% of persons. Very high percentage of men of low physical activity was stated (51%). Higher level of respective risk factors reflected in individual score of CAD risk coefficient fixed on 5 points and being higher than in other studies of different Poland regions populations.

Adult

[Behavior of hydroxyproline in the rat lung following exposure to surface dust and industrial ashes].

There was analysed, by means of biochemical examinations, the behaviour of hydroxyproline level in the lungs of experimental animals exposed to the action of soil dusts and electroenergetic ashes. 44 female white rats of Wistar strain were used in the experiment. The animals were administered intratracheally 0.2 ml dusts and electroenergetic ashes suspension. After decapitation, prepared material was taken from the left lung. Hydroxyproline determinations were performed according to Prokop's und Undenfried's method modified by Tomaszewski and Hanzlik. 9 months after the administration of the dusts, the contents of hydroxyproline slightly differed from the levels observed in control group.

Animals