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Biomedical subjects

G Stein

Publications and source records attributed to G Stein.

At least 73 records · Page 4Linked to original sources
PubMed2000

[Asymptomatic bacteriuria].

With the availability of methods to quantitate microbes in urine, one has come to recognize that a certain proportion of apparently healthy individuals have bacteria in their urine in the absence of any clinical symptoms. By definition, asymptomatic bacteriuria is present, if on 1, 2 or more consecutive occasions > 100,000 colony forming units/ml are found in aseptically collected midstream urine, granted that the same microorganism is isolated. Such asymptomatic bacteriuria is found in 2.7% of women aged between 15 and 24 years and increases to 20 to 50% in women above an age of 80 years. In men the prevalence of asymptomatic bacteriuria is considerably lower, but increases to 6 to 20% above the age of 80 years. The microbe most frequently involved in asymptomatic bacteriuria is Escherichia coli, which is characterized by the expression of multiple virulence factors. In this respect they differ from bacteria found in patients with lower or upper urinary tract infections. There is a consensus that in the absence of anatomical or functional abnormalities of the urinary tract asymptomatic bacteriuria per se does not lead to renal scarring, renal dysfunction, or hypertension. The overall prevalence of asymptomatic bacteriuria in pregnancy varies between 2 and 10% with the very small risk of an acute symptomatic episode of urinary tract infection in early pregnancy, but with a substantial risk (30 to 60%) during the last trimester. There is an association between asymptomatic bacteriuria and low birth weight. Asymptomatic bacteriurias are seen in 4 to 60% of immunosuppressed renal graft recipients. The incidence of asymptomatic bacteriuria is also high among patients with diabetes mellitus; the prevalence is approximately 3 fold higher in adult women (7.9 to 11.1%). In these patients asymptomatic bacteriuria does not carry a renal risk. Renal functional prognosis in uncomplicated asymptomatic bacteriuria is excellent. Therefore asymptomatic bacteriuria should be treated during pregnancy, after renal transplantation, prior to urological interventions and in patients with frequent episodes of symptomatic urinary tract infection.

Adolescent↗
PubMed2000

[The quality of the treatment of diabetics in kidney failure in Germany].

BACKGROUND AND OBJECTIVE: In recent years there has been a rapid increase in the number of dialysis-dependent diabetics in Germany. Survival on dialysis is not satisfactory and damage acquired in the preterminal stage of renal failure is thought to play an important role. Late referral to a nephrologist and insufficient quality of medical management are thought to contribute importantly to poor outcome. This hypothesis was evaluated in the present study. PATIENTS AND METHOD: The data of all 173 diabetic patients (16 with type 1, 157 with type 2 diabetes, 90 men, 83 women, mean age 63.3 [31-95] years), who had been referred in 1996 for the first time to five renal units, were retrospectively assessed using a structured protocol. RESULTS: Patients were usually referred in advanced renal failure (median creatinine clearance 29 ml/min, range 1-216) with insufficient control of systolic (170 [120-260] mmHg) and diastolic blood pressure (90 [60-180] mmHg), insufficient antihypertensive therapy (without treatment 32 of 173 patients; median number of classes of antihypertensive agents used 2 [range 1-6]; ACE inhibitors 79 of 173 patients), high HbA1c (7.9 [4.9-15.7]%) and LDL cholesterol (176 [67-307] mg/dl). Immediate dialysis was required in 45 patients. CONCLUSION: The data document insufficient quality of treatment and late incorporation of a nephrologist into the medical team involved in the care of diabetic patients. Changes in the structure of diabetes care are necessary to improve treatment quality.

Adult↗
PubMed2000

[Erythrocytes in the urine: glomerulonephritis or other source of bleeding. Answer with the microscope].

On the basis of an evaluation of the morphology of erythrocytes in urinary sediment, it is possible to distinguish between nephrological and urological hematuria. In the case of the former, the cells have "disruptive characteristics" (membrane evagination, ring formations, dwarf forms and loss of hemoglobin), enabling them to be distinguished from the regularly formed erythrocytes from hemorrhage within the urinary tract. Dysmorphic erythrocytes retain their characteristic shapes even when persisting in the urine for lengthy periods. An assessment of erythrocyte morphology forms a suitable basis for choosing appropriate further diagnostic measures for urological or nephrological work-up. The method of examination is simple and readily reproducible, and should therefore form an early part of the diagnostic strategy. Microscopic assessment erythrocyte shape is not suitable for the diagnostic work-up of tumors, nor can it obviate the need for kidney biopsy for the investigation of histomorphological changes in glomerular nephritis.

Acanthocytes↗
PubMed2000

High-dose clodronate therapy prevents joint destruction in chronic antigen-induced arthritis of the rat but inhibits bone formation at the axial skeleton.

OBJECTIVE: To investigate the effects of clodronate on clinical disease activity, inflammatory alterations and cartilage destruction, periarticular and axial bone volume and bone turnover in chronic antigen-induced arthritis (AIA; day 28). METHODS: Rats with AIA were treated with clodronate (5 mg/kg/day continuously; 20 mg/kg/day intermittently or high-dose with 300 mg/kg 3 hours after arthritis induction +20 mg/kg/day continuously, respectively). Joint pathology was examined by histology. Bone volume and cellular turnover parameters of the right tibia head and the third lumbar vertebra were evaluated by histomorphometry. The findings were compared with those of healthy controls, sham-treated AIA and AIA treated continuously with 250 microg/kg of dexamethasone. RESULTS: All three therapy regimens with clodronate resulted in a significant reduction of joint swelling, histopathological inflammatory changes and cartilage destruction in comparison with sham-treated AIA. The antiinflammatory effect of high-dose clodronate was comparable with dexamethasone. The intermittent administration of 20 mg/kg/day of clodronate completely prevented periarticular bone loss by reduction of bone resorption without affecting bone formation at the periarticular and axial bone. Both continuous treatment with 5 mg/kg/day of clodronate and high-dose clodronate therapy partially prevented periarticular bone loss and reduced parameters of bone formation at the axial bone to values below those of healthy controls. CONCLUSION: High-dose clodronate therapy exerts an excellent preventive effect on clinical disease activity and on joint destruction in AIA. However, continuous treatment with high doses of clodronate may result in a low turnover state of bone remodelling.

Animals↗
PubMed2000

[The effect of aprotinin and tranexamic acid on fibrinolysis and thrombin generation during cardiopulmonary bypass].

OBJECTIVE: Antifibrinolytic drug therapy has proved to be effective in reducing blood loss associated with cardiac surgery and cardiopulmonary bypass (CPB). Concerns remain regarding the risk of enhancing thrombosis. In the present study we investigated the effect of aprotinin (AP) and tranexamic acid (TA) on fibrinolysis and thrombin generation during CPB. METHODS: 60 patients undergoing coronary artery bypass graft surgery were randomised in 3 groups. They received either aprotinin ("high-dose-scheme"), tranexamic acid (2 g/h) or no antifibrinolytic therapy (control group). Collection of blood was performed at 7 pre-, intra- and postoperatively predetermined intervals. Fibrinolytic activity was determined by measuring concentrations of D-dimer, thrombin generation by the measurement of thrombin-antithrombin III complex (TAT). RESULTS: There was no significant increase of D-dimers in the AP or TA group. D-dimer concentration in the control group increased significantly after starting CPB. Comparing with the control group, thrombin generation in the AP group was significant less, while TA group produced significantly higher values. CONCLUSION: After the administration of AP for cardiac surgery we observed reductions in both intraoperative fibrinolysis and thrombin generation. In case of TA suppression of fibrinolytic activity in the absence of concomitant reduction in thrombin generation occurred. These results suggest that TA could potentiate a hypercoagulable state with the risk of thrombosis in the perioperative setting.

Aged↗
PubMed2000

High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfontiamine.

OBJECTIVE: The influence of either orally administered S-benzoylthiamine-O-monophosphate (benfotiamine) or thiamine nitrate on the thiamine status was tested in a randomised, two-group comparison study in 20 end-stage renal disease (ESRD) patients. Main outcome measures were the pharmacokinetics of thiamine diphosphate (TDP) in blood, the in vitro erythrocyte transketolase activity, its activation coefficient (alpha-ETK) and the TDP concentration in erythrocytes. METHODS: After ingestion of a single dose of either 100 mg thiamine nitrate (corresponding to 305 micromol thiamine) or 100 mg benfotiamine (corresponding to 214 micromol thiamine), the blood levels of thiamine phosphate esters were analysed by means of high-performance liquid chromatography for a 24-h period. The TDP concentration in erythrocytes was calculated using the haematocrit and TDP concentration in blood. Erythrocyte transketolase activity and alpha-ETK were measured before and 10 h after administration. The pharmacokinetics of TDP in blood were compared with healthy subjects of other studies retrieved from database query. RESULTS: Regarding the blood concentrations of TDP, the patients with ESRD had a 4.3 times higher area under the concentration time curve after benfotiamine administration than after thiamine nitrate. After benfotiamine administration, the peak plasma concentration of TDP exceeded that in healthy subjects by 51%. In the ESRD patients, after 24 h, the mean TDP concentration in erythrocytes increased from 158.7+/-30.9 ng/ml initially to 325.8+/-50.9 ng/ml after administration of benfotiamine and from 166.2+/-51.9 ng/ml to 200.5+/-50.0 ng/ml after thiamine nitrate administration. The ratio between the maximum erythrocyte TDP concentration and basal concentration was 2.66+/-0.6 in the benfotiamine group and 1.44+/-0.2 in the group receiving thiamine nitrate (P < 0.001). After 24 h, it was 2.11+/-0.4 and 1.23+/-0.2, respectively. The transketolase activity increased from 3.54+/-0.7 microkat/l initially to 3.84+/-0.6 microkat/l after benfotiamine intake (P = 0.02) and from 3.71+/-0.8 microkat/l to 4.02+/-0.7 microkat/l after thiamine nitrate intake (P = 0.08). Likewise, alpha-ETK decreased from initially 1.10+/-0.07 to 1.04+/-0.04 (P = 0.04) and from 1.12+/-0.05 to 1.08+/-0.06 (P = 0.09). After 24 h, the phosphorylation ratio in whole blood decreased from 12.9+/-6.9 initially to 5.6+/-3.2 after benfotiamine administration (P = 0.02) and from 13.5+/-7.3 to 9.0+/-4.8 (P = 0.03) after administration of thiamine nitrate. No correlation between erythrocyte TDP concentration and transketolase activity and/or alpha-ETK was observed in ESRD patients, either before or 10 h after administration. CONCLUSION: Compared with thiamine nitrate, the oral administration of benfotiamine leads to higher TDP concentrations in erythrocytes accompanied with a significant improvement of the erythrocyte transketolase activity in ESRD patients.

Administration, Oral↗
PubMed2000

PDGF receptor kinase blocker AG1295 attenuates interstitial fibrosis in rat kidney after unilateral obstruction.

The current study was designed to investigate possible effects of the platelet-derived growth factor (PDGF) receptor kinase blocker AG1295 on the development of interstitial fibrosis in rats with unilateral ureteral obstruction (UUO), monitored by ED-A+ fibronectin expression, the number of macrophages, and the presence of myofibroblasts as visualized by immunohistochemistry with monoclonal antibodies (mAb) IST9, mAb ED1, and mAb 1A4, respectively; interstitial fibrosis was quantified by Sirius-Red staining and computer-aided image analysis. Without AG1295 treatment, the Sirius-Red stained area of the control kidneys comprised 6.8 +/- 1.3% of the totally inspected area and increased to 19.0 +/- 1.9% in animals by 14 days and to 23.4 +/- 1.7% by 21 days after UUO. The number of macrophages increased from 4.3 +/- 1.1 in controls to 16.6 +/- 2.6 in animals at 14 days and to 23.2 +/- 4.4 at 21 days after UUO. This was accompanied by an increase in both ED-A+ fibronectin deposition and alpha-smooth muscle actin expression. Treatment with AG1295 (12 mg/kg body weight, daily i.p.) significantly reduced interstitial fibrosis as verified by a smaller Sirius-Red stained area (15.7 +/- 1.9% in animals at 14 days and 17.0 +/- 0.7% at 21 days after UUO) and also by a reduced number of macrophages (12.8 +/- 1.4 in animals at 14 days and 15.5 +/- 3.8 at 21 days after UUO), and by the ED-A+ fibronectin deposition and the number of cells positive for alpha-smooth muscle actin. The study indicates that the PDGF receptor kinase blocker AG1295 is able to decrease interstitial fibrosis in the rat UUO model significantly. The diminution of early fibrosis mediators, i.e., macrophages, ED-A+ fibronectin, and myofibroblast phenotype, points to a modulated fibrosis process via a blockade of PDGF actions.

Actins↗
PubMed2000

Immunochemical detection of imidazolone in uremia and rheumatoid arthritis.

The advanced glycation end-product imidazolone is formed by reaction of arginine with 3-deoxyglucosone (3-DG), a reactive intermediate of the Maillard reaction, whose formation is non-oxidative. Using an antibody specific to this 3-DG-derived AGE, we demonstrated the presence of imidazolone-modified proteins in vivo in the urine and dialysate of patients with chronic renal failure, in the synovial fluid of patients with rheumatoid arthritis, as well as in vitro in human serum and human serum albumin incubated with glucose. Furthermore, we could show that in uremic patients the dimeric form of beta(2)-microglobulin is more susceptible to imidazolone modification than the monomeric one. Thus, the immunochemical detection of imidazolone may be a good marker for 3-DG-derived AGE modification in vivo and in vitro permitting a differentiation between the oxidative and the non-oxidative pathway of AGE generation.

Adult↗
PubMed2000

Expression of LFA-1 (CD11a/CD18) and ICAM-1 (CD54) in an animal model of renal interstitial fibrosis induced by unilateral ureteral obstruction.

Unilateral ureteral obstruction (UUO) has been used as an experimental model to induce tubulointerstitial damage and interstitial fibrosis. UUO is characterized by cellular proliferation, accumulation of inflammatory cells, and subsequent replacement of renal parenchyma by fibrous tissue. The influx of inflammatory cells into the renal interstitium is mediated by adhesion molecules. In this study, the development of fibrosis in the UUO model of the rat was examined and its relation to the time course of LFA-1 and ICAM-1 expression was assessed by immunohistochemistry. An increase in interstitial connective tissue was detected on day 10 after UUO, with a maximum on day 35. After unilateral ureteral obstruction, LFA-1 was prominently expressed in interstitial infiltrates, and to a lesser degree in glomerular areas. An initial increase in LFA-1-positive cells was noted already on day 10, with a maximum on day 20 and a decline on day 25. During the time course of 35 days after UUO, we observed an increase in ICAM-1 expression in the vascular endothelium, in tubular epithelium and in interstitial areas. This study shows that LFA-1 expression and ICAM-1 expression are concordant and that this process is associated with increasing interstitial fibrosis. ICAM-1 interstitial tissue may facilitate the homing and persistence of an interstitial infiltrate by ICAM-1/LFA-1 interactions, thereby preceding the development of renal interstitial fibrosis.

Animals↗
PubMed2000

Assessment of thiamin status in chronic renal failure patients, transplant recipients and hemodialysis patients receiving a multivitamin supplementation.

The thiamin status of patients with chronic renal failure (CRF, n = 14), dialysis patients (DP, n = 24) and patients after renal transplantation (RT, n = 19) was assessed. Thiamin intake was calculated at mean levels of 1.26 mg/d (CRF), 0.83 mg/d (DP) and 1.42 mg/d (RT). Corresponding mean plasma concentrations were 64.2 nmol/l (CRF), 78.3 nmol/l (DP) and 55.1 nmol/l (RT). Thiamin supplements of 1.5 mg or 8.0 mg orally given to patients of the DP-group after each dialysis session showed slightly higher thiamin concentrations in plasma. Transketolase activity coefficients (ETK-AC) were in the same range (1.11...1.19) except for RT-patients who had a slightly but not significantly higher ETK-AC of 1.22. During dialysis treatment (DT), thiamin plasma concentrations dropped to 75 and/or 82% in patients supplemented with 1.5 and/or 8.0 mg. They both reached initial levels again 44 hours later. Despite large inter-individual differences, thiamin concentrations increased in the non-supplemented DP-group. ETK-AC did not change after a 14-day interruption of supplementation and did not deteriorate after a single dialysis session, both in supplemented and non-supplemented patients. A daily thiamin supplementation which complies with the RDA for healthy subjects is indicated in DP and is sufficient to keep thiamin status within the normal range.

Adult↗
PubMed2000

Role of homocysteine, cystathionine and methylmalonic acid measurement for diagnosis of vitamin deficiency in high-aged subjects.

BACKGROUND: Intracellular B-vitamin and folate deficiency indicated by hyperhomocysteinemia is very frequent in the elderly population. Hyperhomocysteinemia increases the risk of atherothrombotic diseases and neuropsychiatric complications. Our aim was to evaluate the prevalence of increased serum metabolite concentrations in subjects of a higher age, and whether the measurement of metabolite concentrations is more effective in diagnosing B-vitamin deficiency than mere homocysteine. MATERIALS AND METHODS: Homocysteine (HCY), cystathionine (CYS) and methylmalonic acid (MMA) were investigated in serum together with vitamin B-12, B-6 and folate in 90 high-aged subjects (85-102 years), 92 seniors (65-75 years), and in 50 younger subjects (19-50 years). RESULTS: Elderly subjects (high-aged and senior) had elevated serum concentrations of metabolites. High-aged subjects had a higher frequency of pathological increases than seniors: HCY 62% vs. 24%; MMA 62% vs. 23%; CYS 81% vs. 36%. Folate and vitamin B-6 concentrations were significantly decreased in both elderly groups; vitamin B-12 was only decreased in high-aged subjects. Utilising vitamin B-6, B-12 and folate for diagnosis of intracellular vitamin deficiency, the rate was 30% in seniors and 55% in high aged subjects. However, utilising the metabolites (HCY, MMA and CYS) for the diagnosis of intracellular vitamin deficiency, there was a distinctly increased rate of 55% in seniors respective to 90% in high-aged subjects. Backward multiple regression analysis revealed that only folate, MMA, creatinine and age were independent variables influencing the HCY concentration. Furthermore, the MMA concentration was significantly and independently influenced by folate, vitamin B-12, HCY and creatinine, and the serum concentration of CYS by vitamin B-12, creatinine and age. CONCLUSION: The metabolites HCY, MMA and CYS are sensitive indicators diagnosing impaired remethylation of homocysteine to methionine with parallel activation of catabolic pathway. Compared to mere HCY or B-vitamins in serum, the efficiency of diagnosing a disturbed HCY metabolism increases very much in utilising the metabolites HCY, MMA and CYS. For differential diagnosis, parallel measurement of folate and creatinine is recommended. The early and correct diagnosis of B-vitamin deficiency in elderly subjects is of high clinical relevance.

Adult↗
PubMed2000

Pharmacodynamics and pharmacokinetics of polyethylene glycol-hirudin in patients with chronic renal failure.

BACKGROUND: Hirudin selectively inhibits thrombin without cofactors and is eliminated via the kidneys. Recombinant hirudin (r-hi) has a terminal elimination half-life (t1/2) of about 50 to 100 minutes. Coupling of polyethylene glycol (PEG) to r-hi, giving PEG-hirudin (PEG-Hi), prolongs its t1/2 while enhancing efficacy. We looked at the pharmacodynamic and pharmacokinetic behavior of PEG-Hi in patients with impaired renal function. METHODS: Anticoagulant activity and the pharmacokinetic parameters of a single intravenous bolus injection of 0.05 mg/kg body weight PEG-Hi were studied in 38 subjects. They were assigned to five groups: group IA, creatinine clearance (CCr) >/= 80 mL/min, 8 healthy volunteers; group IB, CCr >/= 80 mL/min, 8 patients with normal renal function); group II, CCr 79 to 50 mL/min, 7 patients with mild chronic renal failure (CRF); group III, CCr 49 to 20 mL/min, 10 patients with moderate CRF; and group IV, CCr </= 19 mL/min, 5 patients with severe CRF. Plasma and urine samples were collected from patients for up to 120 hours after dosing and from healthy volunteers for up to 24 hours. RESULTS: PEG-Hi was well tolerated in all groups. No serious adverse events were noted. Cmax values were similar in all groups; area under the curve (AUC) increased in patients from 2.9 +/- 1.0 microg. h/mL (IB) to 21.3 +/- 5.0 microg h/mL (IV). According to the severity of renal function, t1/2 was prolonged from 2 hours (IB) to 38.4 hours (IV), while total body clearance (CTB), renal clearance (CRenal), and recovery of PEG-Hi in the urine (FEo-t) decreased as follows: CTB from 23.3 +/- 6.6 (IB) to 2.9 +/- 0.6 mL/min (IV), CRenal from 7.8 +/- 5.0 (IB) to 0.8 +/- 0.5 mL/min (IV), and FEo-t from 40.2 +/- 18. 9% (IB) to 12.6 +/- 13.0% (IV). Total plasma clearance of PEG-Hi was well correlated with CCr. Anti-IIa activity of PEG-Hi showed a closer linear relationship to ecarin clotting time than to activated partial thromboplastin time. CONCLUSION: Hence, PEG-Hi is considered safe in patients with CRF, but dosing and/or dose intervals should be adjusted according to the severity of renal impairment. Ecarin clotting time is well suited for safe and reliable monitoring of PEG-Hi.

Adult↗
PubMed2000

Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure.

BACKGROUND: An excessive rate of cardiac death is a well-known feature of renal failure. Coronary heart disease is frequent and the possibility has been raised that the natural history of the coronary plaque is different in uraemic patients. We assessed the morphology of coronary arteries in patients with end-stage renal failure and compared them with coronary arteries of matched non-uraemic control patients. METHODS: Fifty-four cases were identified at autopsy who met the inclusion criteria: cases, end-stage renal disease (n=27); controls, non-renal patients with coronary artery disease (n=27). At autopsy all three coronary arteries were prepared at corresponding sites for investigations: (i) qualitative analysis (after Stary), (ii) quantitative measurements of intima and media thickness (by planimetry), (iii) immunohistochemical analysis of the coronary plaques and (iv) X-ray diffraction of selected calcified plaques. RESULTS: Qualitative analysis of the coronary arteries showed significantly more calcified plaques of coronary arteries in patients with end-stage renal failure. Plaques of non-uraemic patients were mostly fibroatheromatous. Media thickness of coronary arteries was significantly higher in uraemic patients (187+/-53 microm vs 135+/-29 microm in controls) and intima thickness tended to be higher (158+/-38 microm vs 142+/-31 microm) but this difference was not statistically significant. Plaque area (4.09+/-1. 50 mm(2) vs 4.39+/-0.88 mm(2)) was comparable in both groups. Lumen area, however, was significantly lower in end-stage renal patients. Immunohistochemical analysis of the cellular infiltrate in coronary arteries showed no major differences in these advanced plaques of uraemic and non-uraemic subjects. CONCLUSION: Coronary plaques in patients with end-stage renal failure are characterized by increased media thickness and marked calcification. In contrast to the previous opinion the most marked difference compared to non-uraemic controls does not concern the size, but the composition of the plaque. Deposition of calcium within the plaques may contribute to the high complication rate in uraemic patients.

Aged↗
PubMed2000

31P magnetic resonance spectroscopy in fibromyalgic muscle.

OBJECTIVE: To measure inorganic phosphate (Pi), phosphocreatine (PCr), ATP and phosphodiesters (PDE) in fibromyalgic muscle tissue by (31)P magnetic resonance spectroscopy. METHODS: A 1.5 Tesla scanner with a P 100 surface coil was used to examine 15 patients (mean age 49.9+/-14.3 yr) with fibromyalgia, according to the American College of Rheumatology criteria, and 17 healthy controls (mean age 30.2+/-5.8 yr). RESULTS: Compared with the controls, there were increases in the levels of PDE (+22%, P = 0.032) and Pi (+19%, P = 0.019) in the spectra of fibromyalgia patients, but there was no difference in pH. CONCLUSION: The metabolic differences we found may have been related to weakness and fatigue in the fibromyalgia patients, but they do not fully explain the fibromyalgia symptoms.

Adenosine Triphosphate↗
PubMed2000

Time course of cytokine mRNA expression in kidneys of rats with unilateral ureteral obstruction.

The development of renal interstitial fibrosis (RIF) is related to the expression and excretion of cytokines and growth factors. Thus, we investigated the time course of mRNA expression of cytokines known as causative factors in a model of RIF in rats before and on day 10 after unilateral ureteral obstruction (UUO), when first signs of fibrosis were visible, as well as during progressive RIF. UUO causes a fivefold increase in mRNA expression of monocyte chemoattractant protein 1 15 days after surgery as compared with contralateral kidneys. The level remains elevated about three-fold up to day 25. The mRNA of the fibrogenic cytokine transforming growth factor beta 1 (TGF-beta1) is increased two- to threefold during the time course, whereas the mRNAs of platelet-derived growth factor B chain (PDGF-B) and its receptor beta (PDGF-Rbeta) increase after UUO, reaching their maxima on days 10-15. PDGF-B mRNA increase up to day 15, marking the onset of fibrosis, and decreases thereafter, whereas the expression of the PDGF-Rbeta mRNA remains elevated more than threefold over the entire study period. Incubation of cultured renal fibroblasts with TGF-beta1 and/or PDGF-B suggests that their specific action on cell growth and proliferation is maintained even when they are used in combination. The sustained elevation of TGF-beta1 and PDGF-B/PDGF-Rbeta mRNA levels confirms the assumption of a particular involvement of these cytokines in the pathogenesis of RIF. The mRNA expression of the gap junctional protein connexin 43 in ureteral ligated kidneys is increased sixfold already 5 days after UUO. In this way, the increased connexin 43 mRNA levels indicate a possible function in the remodeling of the kidney tissue after tubular damage and fibrosis.

Animals↗
PubMed1999

A mutant for the yeast scERV1 gene displays a new defect in mitochondrial morphology and distribution.

The yeast scERV1 gene is the best characterized representative of a new gene family found in different lower and higher eukaryotes. The gene product is essential for the yeast cell and has a complex influence on different aspects of mitochondrial biogenesis. The homologous mammalian ALR(Augmenter of Liver Regeneration) genes from man, mouse and rat are important at different developmental stages of the organism as, for example, in spermatogenesis and liver regeneration. In this study the influence of scERV1 on the morphology of mitochondria and its submitochondrial localization are investigated. A temperature-sensitive mutant of the gene was stained with a mitochondria-specific dye and fluorescence was inspected at the permissive and restrictive temperature. A new phenotype for morphological defects of mitochondria was identified. Already at the permissive temperature mitochondrial vesicles accumulate at defined positions in the cell. After shift to the restrictive temperature, morphological changes, and finally complete loss of mitochondrial structures, are observed. Ultrastructural studies confirm these findings and demonstrate the loss of the mitochondrial inner membrane and at the final stage a drastic reduction or complete absence of mitochondria from the cell. GFP fusion experiments with the scERV1 gene and subcellular localization by fractionation experiments identify the gene product inside mitoplasts and the cytosol. Re-investigation of the mutant phenotype demonstrates that after longer incubation of the mutant at the restrictive temperature an irreversible defect of the cells, even on glucose complete medium, is found that is in accordance with a complete loss or irreversible damage of mitochondria.

Cell Polarity↗
PubMed1999

Biosynthesis of osteogenic growth peptide via alternative translational initiation at AUG85 of histone H4 mRNA.

The osteogenic growth peptide (OGP) is an extracellular mitogen identical to the histone H4 (H4) COOH-terminal residues 90-103, which regulates osteogenesis and hematopoiesis. By Northern analysis, OGP mRNA is indistinguishable from H4 mRNA. Indeed, cells transfected with a construct encoding [His102]H4 secreted the corresponding [His13]OGP. These results suggest production of OGP from H4 genes. Cells transfected with H4-chloramphenicol acetyltransferase (CAT) fusion genes expressed both "long" and "short" CAT proteins. The short CAT was retained following an ATG --> TTG mutation of the H4 ATG initiation codon, but not following mutation of the in-frame internal ATG85 codon, which, unlike ATG1, resides within a perfect context for translational initiation. These results suggest that a PreOGP is translated starting at AUG85. The translational initiation at AUG85 could be inhibited by optimizing the nucleotide sequence surrounding ATG1 to maximally support upstream translational initiation, thus implicating leaky ribosomal scanning in usage of the internal AUG. Conversion of the predicted PreOGP to OGP was shown in a cell lysate system using synthetic [His102]H4-(85-103) as substrate. Together, our results demonstrate that H4 gene expression diverges at the translational level into the simultaneous parallel production of both H4, a nuclear structural protein, and OGP, an extracellular regulatory peptide.

Animals↗