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Biomedical subjects

J Olszewski

Publications and source records attributed to J Olszewski.

At least 19 recordsLinked to original sources

A matrix metalloproteinase-generated aggrecan neoepitope as a marker of skeletal maturation and aging in cartilage.

OBJECTIVE: To quantify the matrix metalloproteinase-induced neoepitope F(M/V)DIPEN (Phe-[Met/Val]-Asp-Ile-Pro-Glu-Asn341) in guinea pig and rabbit cartilage during aging. METHODS: Cartilage was taken from the stifle joint, nasal septum, and xiphoid process in guinea pigs and rabbits at selected ages. The cartilage was then extracted and evaluated for F(M/V)DIPEN levels by radioimmunoassay. RESULTS: In the 3 tissues studied, there were major increases in F(M/V)DIPEN levels during skeletal maturation and aging in both the guinea pig and rabbit cartilage. Except for spontaneous osteoarthritis that develops in guinea pigs with aging, increases in the neoepitope were not correlated with arthritis pathology. CONCLUSION: Increases in the level of F(M/V)DIPEN in cartilage occur as a result of skeletal maturation and aging. This physiologic accumulation of F(M/V)DIPEN in cartilage should be considered when using the neoepitope as a disease marker in arthritis.

Age Factors

Quantification of a matrix metalloproteinase-generated aggrecan G1 fragment using monospecific anti-peptide serum.

Several members of the matrix metalloproteinase family have been reported to cleave aggrecan in the interglobular domain between Asn-341 and Phe-342. An antiserum was prepared against a peptide conjugate corresponding to the C-terminal sequence of the matrix metalloproteinase-generated aggrecan G1 fragment (Phe335-Val-Asp-Ile-Pro-Glu-Asn341). A quantitative radioimmunoassay, with a limit of detection of about 80 pM, was developed using this antiserum. This antiserum requires the free carboxyl group of the C-terminal asparagine for optimal recognition. If the C-terminal asparagine is excised from the sequence, replaced with closely related amino acids, or extended across the matrix metalloproteinase cleavage site, there is a 40-10,000-fold loss in detection. Using peptides cleaved from the N-terminus, it was determined that the antiserum requires the entire Phe-Val-Asp-Ile-Pro-Glu-Asn sequence for optimal recognition. The radioimmunoassay detects matrix metalloproteinase-generated G1 fragments with similar sensitivity to the Phe-Val-Asp-Ile-Pro-Glu-Asn peptide, but it does not recognize intact aggrecan. Immunoreactive aggrecan G1 fragments of molecular mass 50 kDa are generated by the matrix metalloproteinases stromelysin and gelatinase A. In contrast, under identical conditions, the closely related metalloproteinases, gelatinase B and collagenase, as well as cathepsin G, cathepsin B and human leucocyte elastase, did not generate a G1 fragment recognized by the antiserum. The anti-Phe-Val-Asp-Ile-Pro-Glu-Asn serum detects stromelysin-generated aggrecan G1 fragments from mouse, guinea pig, rabbit and human, indicating that the detection is not species-specific. This antiserum and radio-immunoassay should be useful for quantifying and characterizing matrix metalloproteinase-generated aggrecan G1 fragments in articular cartilage and synovial fluids from humans and various animal models of articular-cartilage destruction.

Aggrecans

In vivo effects of stromelysin on the composition and physical properties of rabbit articular cartilage in the presence and absence of a synthetic inhibitor.

OBJECTIVE: To characterize the effects of intraarticular injection of recombinant human stromelysin (SLN) on the matrix composition and physical properties of cartilage from lapine stifle joints and the modulation of these effects by the systemic administration of an N-carboxyalkyl synthetic matrix metalloproteinase inhibitor, L-696,418. METHODS: Female 6-8-week-old New Zealand white rabbits received an intraarticular injection of 100 micrograms activated SLN in 1 stifle joint and buffer in the contralateral control knee; these animals were killed after 1 hour. A separate group of animals received an intravenous injection of either 30 mg/kg L-696,418 or buffer prior to intraarticular injection of SLN. Joints were dissected and analyzed for proteoglycan (PG) loss into joint fluid, tissue biochemical composition, and histology by toluidine blue or anti-VDIPEN antibody staining, or were frozen for physical property analysis. Disks of femoropatellar groove cartilage were harvested from the stifle joint and tested in uniaxially confined compression for determination of electromechanical and mechanical properties. RESULTS: Lapine stifle joints that received injection of SLN without systemic administration of L-696,418 showed a 13-fold increase in loss of PG into synovial fluid. Cartilage from these joints showed significant decreases in streaming potential at 1 Hz and electrokinetic coupling coefficient, but no change in equilibrium modulus, dynamic stiffness, or hydraulic permeability. Systemic treatment with L-696,418 resulted in a significant decrease in loss of PG into joint fluid and elimination of changes in cartilage high-frequency streaming potential and coupling coefficient in joints that were injected with SLN. CONCLUSION: The 1-hour exposure to SLN in vivo resulted in loss of PG and exposure of the VDIPEN epitope of the aggrecan core protein in the superficial region of the tissue near the articular surface. This highly localized degradation resulted in electromechanical behavior changes, but little or no change occurred in mechanical properties. Systemic administration of L-696,418 significantly decreased loss of PG from cartilage and prevented the highly localized tissue degradation and the resultant changes in electromechanical behavior caused by intraarticular SLN injection.

Animals

[Changes in levels of human placenta lactogen (hPL), progesterone, and estriol in blood serum and estrogens in urine during gestational diabetes mellitus].

The aim of the study was estimation of endocrinological function of placenta in pregnancy complicated by GDM. The study were performed on a group 13 women with GDM and 14 women in normal pregnancy. All women with GDM were treat by diet and intensive insulinotherapy with self monitoring levels of glucose. In women with GDM level of fructosamine and HbAlc were significant higher but in normal range. In 28, 36, 37, 38, 39 week of pregnancy were determined levels of hPL, oestriol and progesterone in serum and daily excretion of oestrogens in urine. From 36 week of pregnancy levels of hPL, oestriol and progesterone were significant lower in women with GDM. In 39 week of pregnancy level of hPL was 9.34 micrograms/ml vs. 12.71 micrograms/ml, p < 0.01, oestriol was 495.77 nmol/l vs. 681.14 nmol/l, p < 0.01 and progesterone was 25.12 ng/ml vs. 34.52 ng/ml, p < 0.01 respectively in women with GDM and in normal pregnancy.

Adult

[Spirometric examinations at laryngectomized patients and healthy subjects].

Spirometric studies were conducted at 40 patients, divided into on basic group (20 laryngectomized men, aged 48-77 years) and comparative group (20 healthy men, aged 20-57 years). The results obtained showed that the mean value of airways resistance was about 5-times higher than at healthy subjects. The large resistance of airways influence for considerable decreasing of the maximum ventilation volume. Tracheitis and bronchitis chronic in cause of increase resistance of airways at laryngectomized patients and it can influence for quality and understanding of vicarious voice.

Adult

[Changes in levels of chorionic gonadotrophin (hCG) and its subunit alpha and beta in pregnancy complicated by diabetes (GDM)].

The aim of the study was estimation of endocrinological function of placenta in pregnancy complicated by GDM. The study were performed on a group 13 women with GDM and 14 women in normal pregnancy. All women with GDM were treat by diet and intensive insulinotherapy with self monitoring levels of glucose. In women with GDM level of fructosamine and HbAlc were significant higher but in normal range. In 28 and 36 week of pregnancy were determined levels of hCG, alpha hCG, beta hCG, in serum. Level of hCG in control group and in women with GDM were respectively 97.29 U/ml vs. 29.29 U/ml, p < 0.01 in 28 week of pregnancy and 77.23 U/ml vs. 37.93 U/ml, p < 0.05 in 36 week. Level of alpha hCG was lower and beta hCG was higher in group with GDM.

Case-Control Studies

Insulin and sugar concentration changes in mammary secretion in sheep during the periparturient period.

The radioimmunoassayable concentration of insulin in isolated whey fractions of mammary secretion of sheep (n = 28) was measured. The concentrations were high on the last 2 days of pregnancy (550 +/- 80 and 580 +/- 77 microU/ml, respectively), higher on the day of parturition (780 +/- 71 microU/ml) and lower on the next day (290 +/- 54 microU/ml). During the following 4 consecutive days the concentrations gradually decreased to an almost basal blood level (14 microU/ml). The high insulin concentration in the mammary secretion during the periparturient period might be the result of intensified transfer of insulin through the blood-mammary barrier and increasing needs for this hormone by developing mammocytes and probably for the newborn lambs (n = 42) adapting to extra-uterine life. Conversely to the consecutive decrease in insulin, progressively increasing concentrations of sugars in mammary secretions were observed (from 2.1 +/- 0.22% on the second day prior to parturition to 5.5 +/- 0.13% on the fifth day post partum.

Animals

[Multiorgan trauma].

A case is presented of a patient with multiorgan trauma. The main diagnostic problem was coexisting haemorrhage. Curable skin defects were healed after several covering them with intermediate thickness mesh grafts. The postoperative course was complicated with sepsis and acute non-inflammatory renal failure with polyuria.

Abdominal Injuries

[Administration of the cervical torsion test by the examination of Doppler's blood flows in vertebral arteries and basilar artery in patients with degenerative cervical spine changes].

Using the neck rotation test during examination of Doppler's blood flows in vertebral arteries and basilar artery, the authors examined 60 subjects aged 16-60 years, including 20 healthy ones and 40 with cervical spondylarthrosis. The Transpect-TCD was used. Half the patients with cervical spine changes had also receptive hearing damage of low degree. The study demonstrated that neck rotation affected of patological Doppler's blood flows in one or in both vertebral arteries at 50% patients with cervical spondylarthrosis, but without clinical symptoms, and at 70% patients with cervical spondylarthrosis and clinical symptoms. The neck rotation test can have diagnostic significance by examination of sufficiency in vertebrobasilar system, or qualitative significance to microsurgical treatment.

Adolescent

[Diagnostic and therapeutic difficulties in tumors of neck and pharynx encountered in clinical cases].

The authors show case of lateral cervical cyst and carcinoma of the tonsil in woman 50 years, paying attention to large diagnostic and therapeutic difficulties. After operation of the lateral cervical cyst on the left side, metastasis of tumor followed, which was operated (after negative result of the thin-needle biopsy method) and histopathological examination of the tumor didn't prove atypical cells. In a few month after operation there followed tumorous infiltration in region angle of mandibula and in tonsillar region on the side and performed the thin-needle biopsy method showed planoepithelial carcinoma of the tonsil with transitional cells, which infiltrated the lingua, fundus of the oris and lymphonodes of the neck. Next the patient was sent to further treatment in the Oncological Hospital in Lodz. In connexion with advanced of the carcinoma, the using treatment (radiotherapy Co--60 and chemotherapy) was only the palliative treatment and prolongated life of the patient about 3 years.

Biopsy, Needle

Analysis of mRNA decay and rRNA processing in Escherichia coli multiple mutants carrying a deletion in RNase III.

RNase III is an endonuclease involved in processing both rRNA and certain mRNAs. To help determine whether RNase III (rnc) is required for general mRNA turnover in Escherichia coli, we have created a deletion-insertion mutation (delta rnc-38) in the structural gene. In addition, a series of multiple mutant strains containing deficiencies in RNase II (rnb-500), polynucleotide phosphorylase (pnp-7 or pnp-200), RNase E (rne-1 or rne-3071), and RNase III (delta rnc-38) were constructed. The delta rnc-38 single mutant was viable and led to the accumulation of 30S rRNA precursors, as has been previously observed with the rnc-105 allele (P. Gegenheimer, N. Watson, and D. Apirion, J. Biol. Chem. 252:3064-3073, 1977). In the multiple mutant strains, the presence of the delta rnc-38 allele resulted in the more rapid decay of pulse-labeled RNA but did not suppress conditional lethality, suggesting that the lethality associated with altered mRNA turnover may be due to the stabilization of specific mRNAs. In addition, these results indicate that RNase III is probably not required for general mRNA decay. Of particular interest was the observation that the delta rnc-38 rne-1 double mutant did not accumulate 30S rRNA precursors at 30 degrees C, while the delta rnc-38 rne-3071 double mutant did. Possible explanations of these results are discussed.

DNA Mutational Analysis

Computer-aided methods for evaluating cancer risk in miners due to radiation exposure.

The paper presents some aspects of radiation hazard which occurs in a non-nuclear sector of industry, namely radiation hazard in non-uranium underground mines. The radiation hazard is caused in each type of underground mine by the naturally occurring noble radioactive gas-radon (222Rn) and radioactive products of its decay 218Po, 214Pb, 214Bi/214Po the so-called 'radon daughters' occurring in the mines' air. The paper presents the concept of how to provide a reliable system of assessment of miners' exposure by application of representative individual dosimetry, and also presents principles of computer-aided methods for interpretation of the results of miner's dosimetry useful for conversion of dosimetry data to the term of expected risk of cancer caused by exposure at miner's workplaces. The representative Individual Dosimetry system strengthened by computer-aided methods of analysis of results provided essential information on radiation cancer risk for miners employed in coal mines, metal-ore mines, chemical raw material mines in Poland. The coefficient of annual cancer risk induction is 1.5 x 10(-4) year-1 for coal mines, 1.40 x 10(-4) year-1 for metal ore mines and 1.5 x 10(-4) year-1 for chemical raw material mines. The radiation risk appears to be of the same magnitude as the conventional risk of life loss at work-related accidents. The average Lost Life Expectancy coefficient for both the radiation risk and conventional risk are 0.5 and 0.3 year per each miner, respectively.

Electronic Data Processing

Cellular oxidation of low density lipoprotein is caused by thiol production in media containing transition metal ions.

The oxidation of low density lipoprotein (LDL) may be important in atherosclerosis. LDL can be oxidized by cultured cells, including macrophages and endothelial cells. This cellular oxidation is dependent on transition metal ions in the medium. We now report that LDL oxidation by endothelial cells and macrophages is caused by cell-dependent appearance of thiol in the medium ("thiol production"). Thiol appeared in medium when cells were incubated under standard serum-free culture conditions. L-Cystine in the medium was required for thiol production and also for LDL oxidation. Cell-dependent appearance of thiol was inhibited by glutamate (which blocks cystine uptake) and by diethylmaleate (which reacts with thiols). Both compounds also blocked cellular LDL oxidation, even though neither compound had antioxidant activity. Finally, we designed an enzymatic system, based on glutathione reductase, that mimicked cellular thiol production. This enzymatic system caused LDL oxidation, and showed the same dependency for transition metal ions as did cellular LDL oxidation. We conclude that in media containing transition metal ions, cellular oxidation of LDL can be explained by the cell-dependent appearance of thiol in the medium. A very similar mechanism was proposed in 1987 by Heinecke et al. (J. Biol. Chem. 262: 10098-10103). Under other conditions, however, cellular oxidation of LDL may occur by other mechanisms.

Animals

[Determination of natural ionizing radiation exposure near copper mines in Poland].

The results of preliminary tests of natural ionising radiation performed in the area of mining plants and their surroundings have been presented. The survey included measurements of radon concentration and gamma-ray dose rate in free air at 25 locations, 40K, 226Ra and 228Th determination in 48 samples of ore, ore concentrate, floatation tailings, rock and soil as well as 226Ra determination in 11 samples of mine water and river. It was found that the natural radioactivity of ore, rock, concentrate and tailings from mine is higher than the environmental background. For that reason a technologically enhanced natural radiation may occur at some places of mining plants and surrounding areas. Those places must undergo full dosimetric investigation and be under control. It was impossible to estimate how much the environment is contaminated by radon and water coming from mine. However one can say that generally the gamma ray background and radon concentration in free air of this region are at the level considered as a normal.

Air Pollution, Radioactive

[Diagnostic evaluation of the cervical nystagmus in cervical torsion test].

The aim of this work was comparative evaluation of the cervical nystagmus in cervical torsion test with the Nylen's positional nystagmus and their diagnostic value in correlation from anatomical state of cervical column. The authors examined 40 patients with degeneration of cervical spinal column and with normal radiograph of cervical spinal column. The obtained results showed that the cervical nystagmus in cervical torsion test was more frequent (47.5%) than the Nylen's positional nystagmus (37.5%). The cervical nystagmus in cervical torsion test was observed also in health subjects. The authors think that the above mentioned deviations can be caused by the discreet degeneration of cervical spinal column, unseizable in radiograph. The examinations showed that the cervical nystagmus in cervical torsion test could be used simultaneously with the Nylen's positional nystagmus in diagnostic of vertigo, first at all in patients with degeneration of cervical spinal column.

Adolescent

Cellular oxidative modification of low density lipoprotein does not require lipoxygenases.

The oxidative modification of low density lipoprotein (LDL) may play an important role in the pathogenesis of atherosclerosis. LDL can be oxidatively modified in vitro by endothelial cells, mouse peritoneal macrophages, or copper ions. Studies using lipoxygenase inhibitors have suggested that lipoxygenase(s) is required for the cellular modification of LDL [Rankin, S. M., Parthasarathy, S. & Steinberg, D. (1991) J. Lipid Res. 32, 449-456]. We have reexamined the effect of lipoxygenase inhibitors on cellular modification and found that (i) inhibitors specific for 5-lipoxygenase do not block LDL modification; (ii) inhibitors that block lipoxygenase by donating one electron to the enzyme (reductive inactivation) prevent LDL modification by cells and also modification mediated by copper ions, implying that they act as general antioxidants; (iii) the lipoxygenase inhibitor 5,8,11,14-eicosatetraynoic acid blocks 15-lipoxygenase activity in intact macrophages at concentrations 100 times less than those required to block LDL modification by macrophages; and (iv) 5,8,11,14-eicosatetraynoic acid is cytotoxic at concentrations about twice those required to prevent modification. Furthermore, macrophages and the RECB4 line of endothelial cells modify LDL with similar efficiencies despite dramatic differences in 15-lipoxygenase activity. Thus we conclude that neither 5-lipoxygenase nor 15-lipoxygenase is required for modification of LDL by cultured cells.

5,8,11,14-Eicosatetraynoic Acid

Low density lipoprotein is protected from oxidation and the progression of atherosclerosis is slowed in cholesterol-fed rabbits by the antioxidant N,N'-diphenyl-phenylenediamine.

The oxidative modification of low density lipoprotein (LDL) may play an important role in atherosclerosis. We found that the antioxidant N,N'-diphenyl-1,4-phenylenediamine (DPPD) inhibits in vitro LDL oxidation at concentrations much lower than other reported antioxidants. To test whether DPPD could prevent atherosclerosis, New Zealand White rabbits were fed either a diet containing 0.5% cholesterol and 10% corn oil (control group) or the same diet also containing 1% DPPD (DPPD-fed group) for 10 wk. Plasma total cholesterol levels were not different between the two groups, but DPPD feeding increased the levels of triglyceride (73%, P = 0.007) and HDL cholesterol (26%, P = 0.045). Lipoproteins from DPPD-fed rabbits contained DPPD and were much more resistant to oxidation than control lipoproteins. After 10 wk, the DPPD-fed animals had less severe atherosclerosis than did the control animals: thoracic aorta lesion area was decreased by 71% (P = 0.0007), and aortic cholesterol content was decreased by 51% (P = 0.007). Although DPPD cannot be given to humans because it is a mutagen, our results indicate that orally active antioxidants can have antiatherosclerotic activity. This strongly supports the theory that oxidized LDL plays an important role in the pathogenesis of atherosclerosis.

Administration, Oral

[Evaluation of the ear and vestibular apparatus depending on the anatomy of the cervical spine].

Function of the acoustic organ and the vestibular organ in correlation from radiograph of cervical spinal column was examined in 102 patients aged 20-68 years, of both sexes. The obtained results of audiometric and electronystagmographic investigations have shown that the greatest disorders of function of the acoustic organ and the vestibular organ was at the patients with osteophytes and discopathy in cervical spinal column. Impaired hearing and vestibular disorders was observed also at the patients with normal radiograph of cervical spinal column. The authors have thought that the above deviations can be caused by irritation even the discreet degeneration of cervical spinal column, which ones conduct to increased tension of sympathetic system.

Adult