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The most commonly used expression platform for production of recombinant proteins in the methylotrophic yeast Hansenula polymorpha relies on the strong and strictly regulated promoter from the gene encoding peroxisomal enzyme alcohol (or methanol) oxidase (P(MOX)). Expression from P(MOX) is induced by methanol and is partially derepressed in glycerol or xylose medium, whereas in the presence of hexoses, disaccharides or ethanol, it is repressed. The need for methanol for maximal induction of gene expression in large-scale fermentation is a significant drawback, as this compound is toxic, flammable, supports a slow growth rate and requires extensive aeration. We isolated H. polymorpha mutants deficient in glucose repression of P(MOX) due to an impaired HpGCR1 gene, and other yet unidentified secondary mutations. The mutants exhibited pronounced defects in P(MOX) regulation only by hexoses and xylose, but not by disaccharides or ethanol. With one of these mutant strains as hosts, we developed a modified two-carbon source mode expression platform that utilizes convenient sugar substrates for growth (sucrose) and induction of recombinant protein expression (glucose or xylose). We demonstrate efficient regulatable by sugar carbon sources expression of three recombinant proteins: a secreted glucose oxidase from the fungus Aspergillus niger, a secreted mini pro-insulin, and an intracellular hepatitis B virus surface antigen in these mutant hosts. The modified expression platform preserves the favorable regulatable nature of P(MOX) without methanol, making a convenient alternative to the traditional system.

The leucine rich repeat containing 3B (LRRC3B) gene is a putative tumor suppressor located on human chromosome 3 in the 3p24 region. LRRC3B is frequently altered in colon and gastric cancers and also in leukaemias. In this study we investigated the promoter region methylation as a possible mechanism of LRRC3B gene inactivation in clear cell renal cell carcinomas. We found that the LRRC3B gene promoter was methylated in 43% of clear cell renal carcinoma samples. However, no correlation between DNA methylation and LRRC3B expression was found.

FHIT is a tumour suppressor gene which is frequently inactivated in different types of cancer. Both genetic (mutations, deletions, chromosomal rearrangements) and epigenetic (aberrant methylation of the 5'CpG island) alterations of the FHIT gene have been reported in various malignancies. Yet little is known about the mechanism of FHIT inactivation in clear cell renal carcinomas. Since genetic alterations were not frequently observed in DNA corresponding to the FHIT gene in renal tumours, to elucidate the mechanism of FHIT gene silencing we examined 22 paired samples of clear cell renal carcinoma and non-malignant renal tissue for the methylation of the FHIT 5'CpG island by methylation-specific PCR. Hypermethylation of the FHIT 5'CpG island was detected in 54.5% (12/22) of clear cell renal carcinomas. Bisulfite sequencing of the FHIT 5'CpG island confirmed the results obtained by methylation-specific PCR for selected samples. We showed here that expression of the FHIT gene is inversely correlated with hypermethylation of the FHIT 5'CpG island in the selected samples. Our results suggest that hypermethylation of the FHIT 5'CpG island may be responsible for inactivation of the FHIT gene in clear cell renal carcinomas.

Results of treatment of 102 patients aged from 20 to 88 years for postoperative urethrostenosis were analyzed. Complex of investigations had included the analysis of complaints, data of anamnesis, instrumental methods, blood and urine analysis. Special urologic investigation had envisaged the revelation of the uresis disorders signs, conduction of radiologic, ultrasonic investigation, urophlowmetry. Optical urethrotomy, transurethral resection (TUR) of stenosis, bougienage were conducted depending on length of stenosis. In all patients independent controlled uresis was restored, signs of obstruction were eliminated. Introduction of miniinvasive methods of treatment in practice had promoted the lowering of operative intervention risk, the intra- and postoperative complications frequency, duration of intervention, had allowed to avoid performance of open operation, to improve quality of life.

Effects were studied of niftolide in tablets, 0.25 g on a three-times daily basis in combination with low doses of sinestrol, 5 mg intramuscularly within 24 h, on tumor growth, blood plasma content of luteinizing hormone (LH), testosterone (T) and testosterone-estradiol-binding globulin (TEBG) in 46 patients with prostate gland carcinoma, including seven patients with metastases. After treatment for three months, plasma T level decreased by 63%, that of LH by 53% whereas TEBG increased twice as much. The treatments were administered for as long as 10 months, with estrogen therapy being tapered to a dose of 3 mg daily. The above treatment schedule resulted in stabilization or partial regression of tumor growth in as many as 94.9% cases; also deserving to be noticed was improvement in the outflow of urine and alleviation of the pain syndrome. The clinical effect is believed to be due to pharmacological blockade of androgenic receptors in the tumor and its metastases as well as to antigonadotropic activity of estrogen and striking lowering of blood plasma free T.

Results were studied of use of T-activin in those clinical settings related to acute inflammatory diseases of the kidneys. There was a positive clinical effect from this preparation in all twenty-eight patients with acute purulent pyelonephritis, accompanied by readjustments in the patients' immune system. A rise to the norm was found to occur in T-helper counts, and accordingly, immunoregulatory index, NK-cell activity, blood microbocydic activity. The in vitro investigations done suggested the need for individual testing of immunocompetent cells of the patient to optimize the therapy.

As many as 159 patients with chronic pyelonephritis and 100 those with glomerulonephritis residing in ecologically favourable, and on contaminated territories for 6-8 years after Chernobyl accident, were examined for indices of lipid peroxidation, antioxidant system and energy exchange. The above renal disease were found to be accompanied by a rise in the activity of lipid peroxidation and accumulation of excess of their products in cellular membranes and urine. In the antioxidant system, the activity of NAD-H2-dependent factors and an inhibitor of free radical oxidation of superoxiddismutase tends to decrease. There occur changes in isoenzyme spectrum of lactate and malatedehydrogenases. The above shifts appear to be manifest in those persons having been exposed to low radiation doses. Antioxidants and stabilizers of the biological membranes were shown to be useful in correcting the above metabolic processes.

Patients with adenoma of the prostate appear to benefit from application of the unit "Prostatron" in one session without anesthesiologic maintenance and under outpatient conditions in the absolute majority of cases, as evidenced by reports from abroad and our own experience gained in the treatment of patients with adenoma of the prostate. This permits it to be recommended for widespread use in urological settings. Clinical, uroflowmetric and ultrasonic monitoring of the urogenital system status in patients with adenoma of the prostate, which is to be delivered in all such patients,--if used in combination with TUMWT,--becomes a means of really active assessment of treatment effectiveness rather than a passive recording of the moment of worsening of the patient' state.

Conventional routine renography and dynamic renoscintigraphy fail to yield sufficient diagnostic criteria in vasorenal hypertension, being associated with 21.5% false negative and 33.3% false positive results. Capoten induces statistically significant functional changes manifested by worsening of time-associated indicators of secretory-excretory function of the kidney, glomerular filtration rate and effective renal plasma flow on the side of the unilateral renal artery stenosis; relative hypotension in this situation leads to a statistically insignificant improvement of functional activity of the contralateral kidney parenchyma.

With the purpose of improving a differential diagnosis between stress and urgent forms of UI (urinary incontinence), functional condition was studied of lower urinary tract in 62 women suffering from the above pathologies, using general clinical, urologic and neuroelectromyographic methods. In women suffering from urinary incontinence, a decrease is noted of contractile activity of all the anatomical formations responsible for the continence of urine, and the pattern of the electromyograms recorded permits identification of the form of the pathology. The authors hold the view that the onset of an UI symptom in the majority of the examinees is associated with the degenerative dystrophic lesion of the lumbosacral portion of the spine.

Of 507 patients with renal tumours 36 (7.1%) presented with primary epithelial neoplasms of the renal pelvis. Histological investigation revealed benign papillomas in 3 (8.3%) cases. These patients underwent resection of the renal pelvis along with the tumour. Nephro-ureterectomy was performed in 33 patients, of whom 27 (75%) had it for transitional cell carcinoma, 5 (14%) for squamous cell carcinoma and 1 (2.7%) patient for solid carcinoma of the pelvis. Results of surgical treatment vary with the process stage so that the more advanced the stage, the poorer is the prognosis. High efficiency was shown of nephro-ureterectomy. At 5 years 9 of 13 operated on are alive without signs of metastatic disease.

In 22 and 19 patients with vasorenal hypertension the influence of exercise loading and capoten action on renal function accordingly were analyzed using the data obtained with the help of radionuclide renography. In 10 (45.4%) of 22 patients after the bicycle ergometry application the changes in hippuran transport occurred, in 12 (54.6%) the significant changes of renal function was not determined. In patients of these groups the arterial pressure after operation was accordingly 24.0/14.7 kPa (180/110 mm Hg) and 18.7/10.7 kPa (140/80 mm Hg). According to the data obtained with the help of radionuclide renography the curve height lowering was noted in 7 (36.9%) of 19 patients, and after capoten injection--in 18 (94.7%).

Informative value of ultrasonography potential in the diagnosis of nephrotuberculosis was studied by comparison with conventional x-ray and intraoperative findings in 78 relevant patients. Three patterns of renal ultrasonic architectonics changes in nephrotuberculosis were revealed: 1) focal heterogeneity of renal parenchyma, 2) pseudocystic type, 3) hydronephrotic transformation. It is concluded that ultrasonography is superior to routine diagnostic methods, but is recommended for use in combination with standard methods of phthisiourological diagnosis.

Recombinant interferon treatment of donors' and bladder cancer patients' lymphocytes results in activation of natural killer cells which is in correlation with enhanced activity of 2,5-oligoadenylate synthetase in them. The study of sensitivity of bladder cancer cell primary cultures showed that the cells are sensitive to various interferons virtually in all the cases observed as indicated by high synthetase activity. The baseline level of 2,5-oligoadenylate synthetase in tumor cells surpassed that in natural killers from healthy donors which may be related to elevated levels of serum gamma-interferon in the above patients.

42 patients underwent conservative surgery for renal cancer. Conservative surgery was applied in 6 patients with only kidney, in 17--with unilateral cancer and contralateral kidney damaged by urological disease, in 17--with simultaneous tumorous process and in 8 patients with unilateral renal cancer and sound contralateral organ. Terms of postoperative follow-up ranged from 9 to 121 months, 14 patients have died for this period, exacerbation of cancer or metastasis being the cause of death in 9 of them. 5-year survival rate made up 64.4% although with regard to deaths related to cancer it equaled 81%. In 5 patients operated kidneys demonstrated complete functional failure due to nephrosclerosis. 5-year survival rate correlated inversely with advance of the process and was higher in unilateral lesions as compared to that of patients with bilateral tumors.

The role of echo scanning in the diagnosis of acute pyelonephritis was evaluated in 123 patients. It was established that ultrasonography in acute pyelonephritis is a highly informative diagnostic method. The importance is high in acute obstructive pyelonephritis and less informative in acute non-obstructive pyelonephritis. The method has no equal counterparts in the most difficult cases for diagnosis. Association of renal echo scanning with traditional method significantly increases the diagnosis quality.

Enterosgel was used in 89 patients with different stages of renal failure treated surgically and medically. It is concluded that isolated or complex detoxication using enterosgel is a perspective approach in the treatment of patients with surgical renal diseases complicated by chronic renal failure. The use of enterosorption in the preoperative period allows to perform operative intervention in situations when infusion treatment by traditional methods was not sufficient.

The organ-preserving surgical intervention for renal cancer was performed in 42 patients. Five-year survival was 64.4%.

A clinical and immunological study is presented of 1030 practically healthy persons inhabiting Kiev from the moment of the Chernobyl accident. It was established clinically that during the last 5 years more frequent became acute respiratory viral infections, exacerbation of existing infection foci, appearance of complaints of reduced working capacity, somnolence apathy, increased fatiguability, worsening of memory, periodic subfebrility and oth. This symptom complex was determined as the "increased fatiguability syndrome". It was characterized immunologically by different changes showing most frequently a reduction of the functional activity of natural killers. The authors analyze different variants of immunological disorders in this group of subjects and give practical recommendations on using immunotropic drugs. They emphasize the importance of a service of clinical immunology in Ukraine able to organize special services to the population.

A clinical trial of polypeptide prostatic preparation prostatilen has been performed in 37 and 15 patients with chronic prostatitis and prostatic adenoma, respectively. The treatment resulted in attenuation of algetic and dysuria symptoms. Copulative function and spermatogenesis improved. The uroflowmetric index rose, while residual urine and leukocyte count in prostatic secretion reduced. The drug demonstrated antibacterial and immunomodulation effects in the absence of adverse reactions. Prostatilen is indicated in: chronic prostatitis, prostatic adenoma stage I, normospermatogenic and toxic sterility, interoceptive copulative dysfunction, dysuria. The drug in recommended for clinical application.

The paper presents evidence on dysfunction of natural killer cells and abnormal proliferative response of peripheral blood mononuclears to T- and B-cell mitogens (PHA, Phytolacca) in patients at varying stages of acute pyelonephritis. A number of immunomodulators (recombinant alpha 2-interferon, IL-2 and tactivin) produce different effects on natural killer activity and lymphocyte blast transformation in healthy donors and pyelonephritis patients. Immunotropic effects of immunopeptides depend on the drug dose, the response of various subpopulations of the immunocompetent cells being individual. It is suggested that immune system, natural killer activity in particular, plays an important part in pathogenesis of acute pyelonephritis. In vitro experiments demonstrate that there can be a positive clinical response to tactivin and recombinant alpha 2-interferon administered in doses activating the function of certain immunocompetent cells.

The diagnostic possibilities of intravenous digital subtraction angiography (DSA) were evaluated in 2393 patients. The diagnostic value was 97.2%. DSA is contraindicated via the subclavian vein in children, inadequate preparation of the patients, vein abnormalities. The informative value was 92% in vasorenal hypertension, 100% in renal abnormalities, 85% in renal tumours. Intravenous DSA may be a screening method in the diagnosis of hypertension of unclear etiology, abnormalities of the upper urinary tract, while in tumours, especially of small size, DSA is a supplementary method to ultrasound and CT. The method is of economic importance.

The quantitative and functional state of different populations of immunocompetent cells was studied in 45 patients with acute serous and 46 patients with acute purulent pyelonephritis. An imbalance has been found in the system of regulatory cells, activation of phagocytosis with reduction of its reserve capacities, disorders of IL-producing capacity of mononuclears and suppression of the functional activity of NK cells.

With the purpose of improving the results of treatment of chronic prostatitis the authors has reflexotherapy (corporal and auricular). It is shown that the used method has advantages over the existing traditional methods. A multiple-criteria mathematical analysis was carried out of the efficacy of laser reflexotherapy in chronic prostatitis and is was found to equal 89%.

The functional state of urethral neutrophil granulocytes in patients with chronic urethro-prostatitis, and possibility of miramistin use in complex treatment of the disease were investigated. The data revealed functional suppression of these granulocytes in the patients. Complex treatment with miramistin normalized indices of urethral phagocytic activity, on the contrary, after treatment of the patients without the agent there was no tendency to normalize urethral phagocytic function. The findings suggest that miramistin supplemented to routine antiinflammatory therapy improves curative results in patients with chronic urethro-prostatitis but the drug should be prescribed in accordance with the initial function of urethral neutrophil granulocytes.

It was found that addition of mirastimin to the traditional anti-inflammatory treatment results in stimulation of the absorptive capacity of the urethral phagocytes and improves the results of treatment of patients with chronic urethroprostatitis. The immunomodulator mirastimin should be given with consideration of the initial functional state of urethral neutrophilic granulocytes.

The results of treatment with homeopathic remedies in dilutions 10(-400), 10(-2000), 10(-20000) are represented. The informative energetic hologramic conception of homeopathy is proposed. The homeopathic drugs are considered as holograms and the human organic as a biohologram. The resonance is a mode of their interaction with a wide therapeutic effect as a result.

Treatment results were studied in 45 patients with vasorenal hypertension complicated by chronic renal in failure after surgical treatment. Transarterial endarterectomy, roentgen endovascular dilatation of the renal arteries, splenorenal arterial anastomosis, renal autotransplantation were used. A hypotensive effect followed in 21 (46.7%), function improvement in 29 (64.4%). Causes of failures: nephrosclerosis due to prolonged hypertension, concomitant diseases of the upper urinary tract, technical complications of the operation.

Based on the examination of 1050 patients the authors make a conclusion of great significance of renoscintigraphy, ultrasonic scanning and thermography for differential diagnostics of acute pyelonephritis, acute cholecystitis and pancreatitis.

The interrelation between transplantation antigens of the HLA system and predisposition to acute pyelonephritis (PN) were studied in 81 patients, of them 36 with acute serous PN and 45 with acute purulent PN. HLA phenotype was identified with a routine lymphocytotoxic microtest in which a home-made typing panel of HLA antiserum to antigens of A and B loci was used. 150 healthy donors were subjected to control typing. Variance in HLA frequency reliability in patients and controls was verified with chi 2 criterion for tables 2 X 2. The study demonstrated higher frequency of B8 and B14 and lower of Aw19 and B35 antigens in patients with PN versus the healthy controls. Differential analysis with regard to the clinical course of the disease revealed that predisposition to acute serous PN was associated with the occurrence of A3 and B14 antigens while A10 and B8 antigens were indicative of acute purulent PN. It has been stated that purulent PN is developing in presence of secondary deficiency of T and B immune systems. Cross-reacting antigens B14 and B8, as well as splitting antigens A10 and A25 lend more ground to varying clinical course of the disease. HLA antigen B35 is found associated with the development of acute PN resistance.

On the basis of mathematical-statistical analysis of clinical data, 5 risk degrees permitting to predict the course of the disease were distinguished. An algorithm for management of the urologic patients is suggested.

A study of urological patients confirmed the therapeutic effect of homeopathic agents in high dilutions. According to authors' concept the acting basis of this treatment is the information-force field appearing in the diluent and increasing in the course of subsequent dilutions of the agent. The application point are the higher regulatory centers of the body.