Studies of the DNA binding affinity of fetal rat liver nucleoproteins to the alpha 1-acid glycoprotein gene promotor.
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Biomedical subjects
Publications and source records attributed to M Petrović.
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We report here a patient with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) in chronic phase in whom the alkaline phosphatase activity of neutrophils in the peripheral blood was low while at the same time the alkaline phosphatase content of neutrophils present in the urine was elevated. This observation provides independent clinical support for the recent experimental finding that an extrinsic factor (granulocyte colony-stimulating factor) controls alkaline phosphatase expression in human neutrophils.
Acute-phase protein (APR) synthesis was studied under conditions in which the acute-phase response to a sublethal scald was interrupted at the onset of APR synthesis by the infliction of a second scald that overwhelmed the defense mechanisms. The rate of APR synthesis increased shortly after the second scald and then declined rapidly to the control level. At this time point, APR messenger RNA (mRNA) concentrations exceeded severalfold the control values, whereas the APR gene transcription rates fell to the control level. These mRNAs were active in APR synthesis in a cell-free system, as well as in hepatocytes grown in a standard culture medium. These results and those demonstrating a drop in the free amino acid pool level in the liver after the second scald suggested that the lethal outcome was preceded by an impaired supply of liver cells with amino acids and resulting inhibition of APR mRNA translation. Changes in amino acid transport were considered to occur secondarily to those causing hypovolemia and circulatory shock.
This study analysed the concentrations of thyroid binding globulin (TBG) in the serum as well as the level of triiodothyronine (T3), thyroxine (T4), thyreostimulating hormone (TSH), thyroglobulin (Tg) and T4/TBG coefficient, before therapy and on the fifth day of therapy in 27 patients of both sexes suffering from neoplasia. The patients were treated with cytostatic antibiotics, alkylating agents and podophyllines derivates, by protocol. Serum T3 gains in concentration already after 5 days since the beginning of treatment (from 1.65 +/- 0.20 to 1.73 +/- 0.18 nmol/l), but it is retained within physiological ranges as well as TSH, rT3 and Tg. Thyroxine remains within the permitted ranges, but slightly decreased after therapy (64.00 +/- 11.00 nmol/l, mean +/- SEM) in comparison to the value before (71.00 +/- 19.00), p(F) less than 0.1. A reduction of concentrations in total serum proteins at an average 7.88% was found. The level of inter-alpha globulin, TBG, in patients with proved malignancy is low before therapy (14.97 +/- 4.73 micrograms/l, mean +/- SEM, in males and 14.83 +/- 3.70 in females) but, with application of cytostatics it decreases considerably to the level of 11.68 +/- 4.46 (p less than 0.05) in males and to 13.68 +/- 3.89 in females (NS). In view of these facts, T4/TBG coefficient remains normal and contributes to the maintenance of euthyroid gland function.
Leukocyte counts, hemoglobin concentration, PAS positivity index in lymphocytes, leukocyte alkaline phosphatase, karyotype, HLA phenotype as wall as the quality of the cellular and humoral immunity have been studied in 45 patients with chronic lymphocytic leukemia (CLL) and in 103 their closest relatives (sibs, parents). The aim was to detect the possible preleukemic condition in the relatives as a strong propensity towards developing has been previously established in families of patients with CLL. In the CLL patients our studies have confirmed the results of the determination of similar parameters by other authors, namely a higher percentage of PAS+ lymphocytes than normal together with a variety of humoral and cellular immunity disturbances. Regarding the morphological and cytochemical changes in lymphocytes in family members of the CLL patients a higher frequency of PAS+ lymphocytes have been observed: it has been established in over 10 per cent lymphocytes (normally 4-8 per cent) in 31 (30%) examinees and in 14 (13.5%) of these persons the percentage of PAS positivity was equal to that found in CLL patients. Cellular immunity examinations established that in one third of examined E rossete counts counts were lower and in 2 persons the degree of this decrease corresponded to the decrease observed in CLL patients. In one fifth of the examined family members T4:T8 ratio was reduced. In the 13 per cent of the examined M rossete counts were increased, a fact which supports the notion that immunity of B cells exists in relatives of CLL patients. The authors contend that the increased percentage of PAS+ lymphocytes and inadequate functional maturity of the T and B cells in a relatively large number of family members of the CLL patients, intimates that a hereditary disturbance in the lymphocyte make up and their role in the immunity pathways exists and could possibly represent one of the factors implicated in a high frequency of CLL in some families.
At 12 h after scalding of rats a doubling of the hepatocyte nuclear DNA content, which arose from the presence of additional complete genomes and not from amplification of genes coding for the major acute-phase proteins or albumin, was observed. Examination of relative transcription rates per control DNA mass revealed that alpha 1-acid-glycoprotein and cysteine-proteinase-inhibitor genes remained constitutive, alpha- and gamma-fibrinogen and haptoglobin genes underwent transcriptional activation for 290 and 339% respectively, whereas the relative transcription rate of albumin decreased to 65% of the control level. Along with these changes, the alpha 1-acid glycoprotein, cysteine-proteinase inhibitor and the fibrinogen mRNA concentrations increased about 500%, haptoglobin mRNA 250%, whereas the albumin mRNA concentration fell to 86% of the control. The regulation of the mRNA levels was assessed by comparing the relative change in transcription rates expressed per control DNA content with the relative changes of mRNA concentrations. We arrived at the conclusion that the concentrations of alpha 1-acid-glycoprotein and cysteine-proteinase-inhibitor mRNAs were predominantly regulated by a post-transcriptional mechanism, albumin mRNA by a transcriptional mechanism, and the fibrinogen and haptoglobin mRNAs by a combination of both. The degree of change of the serum levels of the examined proteins was similar to that of their mRNA concentrations and was the result of the complete use of the available RNA templates in protein synthesis.
The Teffect of haemodialysis on the level of TBG and thyroid hormones in the serum of patients, suffering from terminal form of kidney insufficiency, were investigated. It was established that in the majority of patients euthyroid function of the thyroid gland was preserved. According to our results this preservation of euthyroid function results from the decreased concentration of sera TBG, which follows the decrease of total sera proteins as well as increased peripheral conversion of thyroxine mostly in rT3.
The time course of changes in the concentrations of individual acute-phase proteins (APRs) in the plasma was examined in the model of rats exposed to a single (sublethal) and repeated (fatal) scalding. These data were interrelated with the rate of survival, plasma volume, corticosterone level, and immunosuppressive potency of the serum. The infliction of a sublethal scalding composing 20% body surface area resulted in an initial 50% reduction of the plasma volume and a severalfold increase of the corticosterone level and immunosuppressive activity of the serum. A subsequent normalisation of these deviations proceeded in parallel with an increased rate of APR synthesis. An early infliction of a second scald was fatal. It led to a 60% reduction of the plasma volume, a lack of plasma APRs, and an additional enhancement of the immunosuppressive activity of serum.
This study analyses frequency of complications and mortality after elective splenectomy done for various hematological diseases, dependent on the spleen weight. From 1979 to 1988 year, 236 patients were treated by splenectomy for various haematological disorders, including: autoimmune disorders (90), Hodgkin's disease (34), lymphoproliferative diseases (96) and myeloproliferative diseases (16 patients). In the early postoperative period, complications occurred in 51 (21.61%) patients, 10 of which (4.24%) died. Considering the size of the spleen (more or less than 1500 gr) there was no difference in the early postoperative mortality (p greater than 0.05; 3.30%:5.38%), while postoperative complications occurred significantly more often in patients with massive splenomegaly (p greater than 0.05; 1259%:3548%). The most frequent complications were septical (8.90%), prolonged fever (5.51 x), and postoperative bleeding (2.97%), while cardial, pulmonary and urinary complications occurred seldom, but more often caused patient's death. Defining the appropriate indications for splenectomy, performing suitable preoperative preparations and postoperative care, mortality was diminished from 7.14% in the period, 1979-1983 year, to 2.17% in the period 1984-1988.
Clinical experience in the treatment of retroperitoneal soft tissue sarcomas during period 1978-1987 is presented. The material consists of 64 patients with the male predominance (60.94%), and the peak occurrence in the forth and fifth decade of life. The difficulties in the diagnostic of these tumours are mostly caused by unspecific clinical picture, which is usually cleared with the stage of inoperability. Modern diagnostic approach, using echotomography and angiography enables earlier diagnosis. The most often seen histological pictures in this series are: M. Hodgkin (28.14%), Liposarcoma (25%) Lympho and fibrosarcoma (twice 12.5%), and the other forms are rarely encountered (1-3%). The operability is very low, and the radical operation is performed only in 16 cases (25.50%), and exploratory procedures are performed in 44 (68.75%). In the rest of cases a reduction of bulk mass of tumour was performed. The 5 year survival in the radically operated is present in 25% (4 patients) what is in accordance with the literature. In the cases with exploration or partial resection, the average survival is 4.5 months, in spite of some longer survivals in the group with Hodgkin's disease, mostly because of the modern cytostatic treatment. Intermediate postoperative mortality is 3.12% (2 patients). In recent years, the more aggressive surgical approach is advised, resulting in better outcome.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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Relative changes in acute-phase protein and albumin mRNAs from the liver of rats exposed to sublethal and lethal scaldings were examined by hybridization and cell-free translation. Infliction of a sublethal scalding comprising 20 per cent of the total skin area resulted in a seven-fold increase of alpha 1-acid glycoprotein (AGP), alpha 1-cysteine protease inhibitor (CPI) and the alpha- and gamma-fibrinogens' (Fb) mRNAs, whereas the level of haptoglobin (Hp) mRNA increased three times. The simultaneous infliction of two such sublethal scaldings were lethal and accompanied by a significant decrease in the concentration of AGP while the levels of CPI. Hp and Fb mRNAs remained similar to those observed after a single 20 per cent injury. A 4 h time delay between the two scaldings was also fatal and followed by an additional increase in Hp mRNA concentration whereas the levels of the other mRNAs were close to those observed after a single 20 per cent scalding. These results demonstrated that the fatal effect of the second scalding was not related to any inhibition of acute-phase reactants mRNA synthesis in the liver.
The 5.56-mm caliber SS 109 projectile was fired from 7.7'' and 12'' twist rifles, respectively, into soap blocks and porcine thighs at 50-metre range using a standardized experimental setup. For comparison, the effects of the 5.56-mm M 193 bullet fired from the 7.7'' twist barrel and M-16 assault rifle were tested. The volume of residual cavity in soap, the shape and sizes of live tissue wounds, and the mass of surgically debrided devitalized tissue were measured. The effects of the two projectiles at 7.7'' twist were found similar in soap; the SS 109 produced more tissue damage than the M 193 missile. Using the 12" twist rifle, a significant increase in wounding capacity of SS 109 projectile was found. In conclusion, nonsignificant differences in local effects between the two projectiles using the 7.7'' twist rifles were found, and markedly increased effects of the SS 109--12'' system were ascribed to decreased essential stability and its earlier tumbling in penetrating a target. The soap as a live tissue simulant has proven its reliability in testing small-caliber arms.
Dark August rats exhibit clinically and histologically verified experimental allergic encephalomyelitis (EAE) when immunized with appropriate antigen (nervous tissue, myelin basic protein) emulsified in complete Freund's adjuvant (CFA). We provide evidence that 6,6'-trechalose dymicolate (TDM) incorporated in incomplete Freund's adjuvant replaces CFA in EAE induction. The animals that recovered from EAE were resistant to the reinduction of the disease irrespectively whether Mycobacterium tuberculosis or TDM was used as an adjuvant. Finally, pretreatment with CFA alone was sufficient for prevention of disease elicited by challenge with encephalitogen + CFA. However, TDM, despite its adjuvant capacity when applied prior to the induction of the disease with encephalitogen + CFA, did not exhibit any protective effect. Thus, our study implicates that adjuvant and suppressive capacities of M. tuberculosis may be related to the different determinants of the microorganisms, TDM possessing the adjuvanticity only.