Biomedical subjects

Z Sandor

Publications and source records attributed to Z Sandor.

At least 19 recordsLinked to original sources

PubMed2001

Trace metal levels in freshwater fish, sediment and water.

The trace metal concentrations in water, sediment and aquatic organisms, such as fish, could indicate the level and tendency of the pollution. This is important not only for the protection of the environment, but for evaluation of the quality of fish meat either captured from natural waters or cultured in fishponds. The total trace metal concentrations in samples of fish from different regions of Hungary and from different species have been determined by using an X-ray fluorescence technique (EDXRF). Water, sediment and fish samples from fishpond systems with different feeding and stocking has also been analyzed. In the case of zinc contents, differences have been traced between the cultured and wild common carp. In the case of common carp reared under different feeding conditions, differences were also observed in the zinc concentration. The retention of the trace metals in the fish has been studied by measuring the levels in sediment, water and feed. The different retention can be explained by the different availability of zinc in the applied feeds, which can be related to the presence of different metal species in the feeds.

Animals↗

PubMed1999

Sjögren's syndrome: lymphoma predisposition coupled with a reduced frequency of t(14;18) translocations in blood lymphocytes.

Sjögren's syndrome (SS) is a systemic autoimmune disorder with a strong tumor predisposition (a 44-fold elevated incidence of non-Hodgkin's lymphoma has been reported). By polymerase chain reaction analysis of t(14;18), a key lymphomagenic event in peripheral blood lymphocytes, we found a lower frequency in a subset of 12 SS patients positive for SS-A/SS-B autoantibodies than in 21 healthy subjects and 20 SS patients lacking these SS marker autoantibodies (P < 0.001). All 14 mutants sequenced displayed signs typical of V(D)J recombinase activity. This perplexing result of a low rate of t(14;18) in a population strongly predisposed to t(14;18)-associated tumor development may be explained by a constitutive deficiency in V(D)J recombinase leading to autoimmunity and increased lymphoproliferation.

Antibodies, Antinuclear↗

PubMed1998

Radiation-induced enterocolitis: basic and applied science.

We adapted and introduced in our laboratory a simplified animal model of radiation-induced enterocolitis. After a shielding of the parenchymatous organs, our dose-response studies revealed that 20 Gy x-ray radiation resulted in about 20% mortality and reproducible lesions in the terminal ileum and proximal colon. These changes are optimal for pharmacologic studies since they may be decreased or aggravated by drugs. Sucralfate dose-dependently decreased the clinical signs of enterocolitis (e.g., lethargy, diarrhea) as well as the number and area of ileal and colonic erosions and ulcers. The wet weight of the ileum and colon were also decreased by sucralfate. bFGF at the small doses used exerted a beneficial effect only on a few of the parameters of enterocolitis. Thus sucralfate, and maybe bFGF, might decrease the severity and accelerate the healing of radiation-induced enterocolitis.

Animals↗

PubMed1998

The diagnostic and prognostic value of tumor angiogenesis.

The "angiogenic switch" and tumor angiogenesis play a critical role in the growth and metastasis of solid tumors. Tumor angiogenesis is regulated by a balance of stimulators (e.g., VEGF, bFGF) and inhibitors of angiogenesis (e.g., angiostatin, endostatin, angiostatic steroids). Measuring angiogenesis (blood vessel density) and/or its main regulators such as VEGF and bFGF in solid tumors, or the levels of these growth factors in the serum or urine provides new and sensitive markers for tumor progression, metastasis and prognosis.

Endothelial Growth Factors↗

PubMed1998

Vascular approach to gastroduodenal ulceration: new studies with endothelins and VEGF.

Endothelins (ET) and VEGF/VPF (vascular endothelial growth factor/vascular permeability factor) are products mainly of endothelial cells, which are also regulated via autocrine and paracrine pathways by these peptides. As a follow-up to our focus on vascular factors in ulcer pathogenesis and healing, we review here our recent studies with ET-1 and VEGF/VPF in animal models and human subjects. Our new results demonstrated a rapid and time-dependent release of ET-1 into the systemic circulation after intragastric administration of ethanol or HCI in rats, and ethanol in humans. The ET-1 release preceded the development of hemorrhagic erosions in both species and might be used as a diagnostic tool to noninvasively quantify acute gastric mucosal lesions. The development of solitary duodenal ulcers in the rat was preceded only by an organ- (involving only the duodenum and not the stomach) and molecule-specific (induced only by cysteamine and not by the nonulcerogenic analog ethanolamine) rapid local release of ET-1. The severity of cysteamine-induced duodenal ulcers was dose-dependently decreased by pretreatment with ET-1 antibodies or antagonist bosentan. A single intragastric dose of VEGF/VPF resulted in gastroprotection against ethanol, while daily intragastric treatment with the peptide for three weeks stimulated angiogenesis in the base of cysteamine-induced duodenal ulcers and accelerated ulcer healing. Thus, modulation of vascular factors seems to be sufficient for both acute gastroprotection and chronic duodenal ulcer healing.

Animals↗

PubMed1996

Basic fibroblast growth factor and PDGF in GI diseases.

This chapter is focused on the relatively recent investigations demonstrating a pharmacological and pathophysiological role for bFGF and PDGF in ulcerative and inflammatory lesions in the upper and lower GI tract. Our initial animal model experiment revealed a potent healing of chronic cysteamine-induced duodenal ulcer in rats treated by intragastric administration of bFGF-w, the acid-resistant bFGF-CS23 or PDGF-BB without decreasing gastric acid secretion or concentration. Subsequently we and others have demonstrated that these peptides accelerate the healing of chronic gastric ulcers, chronic erosive gastritis and ulcerative colitis. Contrary to the potent ulcer healing properties of bFGF and PDGF, these growth factors exert no or modest acute gastroprotection. Nevertheless, new biochemical, molecular biological and immunohistochemical studies indicate that both bFGF and PDGF play a pathophysiological role in the natural history of ulcer healing.

Animals↗

PubMed1995

Deficient DNA repair of triple helix-directed double psoralen damage in human cells.

Damage induced by a single psoralen-modified triple helix-forming oligonucleotide has been reported to be efficiently repaired in human cells. In this study we investigated a set of psoralen coupled oligonucleotides introducing multiple lesions into the target DNA. A simian virus 40 (SV40) shuttle vector was in vitro treated with different triple helix-forming oligonucleotides and UVA radiation, leading to double psoralen adducts at the supF mutational target gene of the plasmid. After passage in the Raji human cell line the recovered vector was analysed in an indicator bacterial strain. The results show that double psoralen adducts, located at both ends of a long triple helix, cannot be repaired efficiently in human cells.

Base Sequence↗

PubMed1995

Triple helix directed psoralen adducts induce a low frequency of recombination in an SV40 shuttle vector.

Triple helix forming oligonucleotide directed psoralen adducts in a mammalian shuttle vector have been reported to be repaired efficiently in human cells. In this study we examined the role of intermolecular homologous recombination in triple helix targeted psoralen adduct repair. A simian virus 40 (SV40) shuttle vector carrying a mutated supF gene was treated with a triplex forming oligonucleotide psoralen conjugate and cotransfected into human cells with a second plasmid bearing the wild type supF gene. Recombinants with a reactivated marker gene were detected by an X-gal assay in indicator bacteria. We could observe a low frequency of psoralen adduct induced recombination indicating that recombination does not play a major role in triplex directed psoralen adduct repair. The implications for targeted mutagenesis by triple helix forming oligonucleotides are discussed.

Base Sequence↗

PubMed1995

Mutational response of Fanconi anaemia cells to shuttle vector site-specific psoralen cross-links.

Fanconi anaemia (FA) is a hereditary tumour-prone disorder. FA cells exposed to DNA crosslinking agents show an increased frequency of chromosome aberrations and of deletion type mutations. The molecular basis of FA presumably is a deficiency in cellular repair of DNA adducts. In this work a shuttle vector plasmid was treated with 8-methoxypsoralen + a split dose of UVA (leading to crosslink induction), and transfected into FA lymphoblasts. The supF gene of the vector showed a mutation frequency similar to that of normal cells; however, the number of base substitutions was relatively low, whereas a high level (50%) of deletions was seen. With both normal and FA cells these deletions varied greatly in size and were randomly distributed within the supF gene. DNA cross-links were also induced using a triple helix forming 22-mer oligonucleotide linked to a psoralen molecule and being complementary to part of supF, leading to a > 30-fold increase of mutations, which were mainly position 167 single-base substitutions and showed a pattern identical to that of the normal cells. This normal response of FA cells to the site-specific DNA cross-links may reflect that not all gene sequences of FA cells are subjected to abnormal DNA repair. Alternatively, it may reflect a lower than normal genome-overall activity of a DNA cross-link repair complex, fully capable of efficiently repairing only molecules carrying relatively few adducts.

Base Sequence↗

PubMed1995

Stimulation of mucosal glutathione and angiogenesis: new mechanisms of gastroprotection and ulcer healing by sucralfate.

BACKGROUND: Among the endogenous mediators (e.g., PG, SH) of gastroprotection, so far only PG was implicated in the mechanism of acute gastroprotection by sucralfate. Angiogenesis, which is stimulated by bFGF, is a recently recognized element in ulcer healing, and sucralfate binds bFGF in vitro and in vivo. METHODS: In fasted rats the gastric mucosal concentration of GSH and protein SH was measured at 30, 60, 120, and 240 min after a single gastroprotective dose of sucralfate. In normally fed rats, angiogenesis was measured in the subcutaneous sponge assay 7 days after the implantation of sponges containing sucralfate and/or bFGF. RESULTS: A gastroprotective dose of sucralfate time-dependently increased GSH concentration in the gastric mucosa. Sucralfate alone accelerated angiogenesis, which was significantly enhanced by combination with an ineffective dose of bFGF in the subcutaneous sponge assay. The same dose of sucralfate combined with an angiogenic dose of bFGF also resulted in synergistic stimulation (e.g., more than fivefold) of angiogenesis. CONCLUSIONS: It appears that elevated mucosal GSH concentration may represent a new factor in the mechanism of acute gastroprotection by sucralfate, and stimulation of angiogenesis is one of the mechanisms of ulcer healing by sucralfate.

Animals↗

PubMed1995

Molecular and cellular basis of ulcer healing.

BACKGROUND: The high ulcer recurrence rates after treatment with antacids or antisecretory drugs illustrate the need for direct treatment of GI ulcers by stimulating repair and healing mechanisms. The molecular regulators of ulcer healing include polyamines and growth factors such as EGF, TGF-beta, bFGF and PDGF. METHODS AND RESULTS: Oral treatment of rats with bFGF or PDGF accelerated the healing of chronic cysteamine-induced duodenal ulcers without decreasing gastric secretion. We found that sucralfate binds bFGF in vitro and in vivo, and the elevated local concentration of this growth factor may contribute to the ulcer healing properties of sucralfate. Parallel treatment with bFGF + sucralfate resulted in synergistic healing of chronic duodenal ulcers and chronic gastritis. CONCLUSIONS: Rapid changes in mucosal concentration of bFGF and EGF receptors during ulceration suggest that these peptides play a role in the natural history of GI ulcers. Thus, treatment based on molecular and cellular mechanisms of ulcer healing allows a direct and efficient ulcer therapy.

Animals↗

PubMed1995

Different molecular forms of basic fibroblast growth factor (bFGF) accelerate duodenal ulcer healing in rats.

UNLABELLED: Basic fibroblast growth factor is an angiogenic polypeptide that exhibits potent antiulcer activity without decreasing gastric acid or pepsin secretion. In this study, we investigated the effect of three acid-stable derivatives of human recombinant bFGF (hrbFGF) on the healing of chronic duodenal ulcer in rats. In Sprague-Dawley female rats, duodenal ulcers were induced by cysteamine-HCl. After laparotomy, rats were randomized to create six groups with homogeneously severe ulcers (perforated or penetrated into the liver or pancreas) and treated by gavage twice a day for 3 weeks with a) vehicle, b) cimetidine (10 mg/100 g), c) Ser78,96-hrbFGF (bioequivalent to rbFGF-CS23), d) CMC-hrbFGF, a carboxymethyl cysteine derivative of hrbFGF or e) PEG-hrbFGF, a polyethylene glycol derivative of hrbFGF. The peptides were administered at 100 ng/100 g. Autopsy was performed on the 21st day, and the ulcer size was measured. The ulcer sizes (mm2) were reduced from 10.3 +/- 1.8 in controls to 4.8 +/- 1.4* after cimetidine treatment and to 5.0 +/- 2.4, 4.2 +/- 1.1* and 0.5 +/- 0.2**, respectively, after administration of aforementioned hrbFGF derivatives (*P < .05; **P < .01 vs. vehicle group), which also significantly enhanced angiogenesis in the ulcer bed. CONCLUSIONS: 1) Oral administration of novel derivatives of hrbFGF accelerated the healing of cysteamine-induced chronic duodenal ulcer. 2) The PEG-hrbFGF derivative was more active than the other hrbFGF analogs. 3) The naturally occurring bFGF provides a good prototype to design new locally acting antiulcer drugs.

Animals↗

PubMed1995

Growth factors: new 'endogenous drugs' for ulcer healing.

BACKGROUND: The pathogenesis of gastroduodenal ulceration has been investigated mostly from the point of view of aggressive factors; the therapeutic interventions affected the healing process only indirectly. With the discovery of the potent healing capacity of growth factors, direct treatment of ulcers is now possible regardless of HCl and pepsin secretion. We review our recent data on how growth factors (e.g., bFGF, PDGF in comparison with EGF) can promote ulcer healing. RESULTS: Treatment of rats with bFGF, PDGF accelerated the healing of experimental chronic duodenal and gastric ulcers without suppressing gastric acid secretion and resulted in superior quality of ulcers healed. We also detected additive or synergistic action between bFGF and cimetidine or bFGF and sucralfate in the healing of chemically induced chronic duodenal ulcers and chronic erosive gastritis. CONCLUSIONS: We conclude that growth factors such as bFGF, PDGF can promote ulcer healing without the need to neutralize gastric secretion and may lead to a direct and efficient therapeutic regime.

Animals↗

PubMed1994

Repair of triple helix directed psoralen adducts in human cells.

Triple helix forming oligonucleotides can direct DNA damaging agents at specific sites in an intact double helix. In our study, triple helix formation was demonstrated in a SV40 based shuttle vector treated with psoralen linked to a 22-mer purine rich oligonucleotide. UVA irradiation caused a covalent linkage of the oligonucleotide through the psoralen to the mutational supF marker gene of the plasmid. After passage in the Jurkat human cell line the recovered vector was analysed in an indicator bacterial strain and mutants were collected. The presence of adducts in the target sequence did not reduce the yield of replicated progeny vector molecules, indicating repair of triple helix associated monoadducts and cross-links. Mutations were highly targeted to a six nucleotide long region of the target sequence. The number of target sequence mutants obtained after triple helix directed psoralen treatment was approximately 160 times higher than with free psoralen. A further investigation of the exact mechanism of the mutational process could make triple helix directed mutagenesis a more useful tool in gene therapy, antiviral therapy, and in studies on DNA repair and genome organisation.

Base Sequence↗

PubMed1994

A reduced level of multiple mutation in a shuttle vector passaged in Sjögren's syndrome cells.

Sjögren's syndrome is a systemic disorder with unknown etiology, displaying many signs of autoimmunity. Although the basic mechanism of this disease is unknown, a defect in somatic mutagenesis of antibody genes has been suggested. Using a shuttle vector plasmid, we here show that the number of vectors with multiple base changes in a marker gene was reduced in B cell lines from two patients with Sjögren's syndrome (8% in both), as compared with values reported for cell lines from normal human donors (16-27%). This finding suggests that a reduction of the rate of somatic mutagenesis may influence the development of symptoms in Sjögren patients.

B-Lymphocytes↗

PubMed1991

Improved outcome of cadaveric renal transplantation due to calcium channel blockers.

Calcium channel blockers (CCB) administered to recipients of cadaveric renal transplants have been shown to improve graft function, decrease the incidence of delayed function, prevent acute cyclosporine toxicity, and lessen the number of rejection episodes in the first several weeks posttransplant. In order to determine whether CCB provide a similar long-term benefit, a retrospective analysis of 83 first cadaveric renal transplants performed in 1987 and 1988 was performed. The clinical course of 17 patients who were discharged and maintained on CCB therapy for 1 year was compared with that of 24 patients who never received CCB during the same 1-year period. The remaining 42 patients were excluded for failing to meet these inclusion criteria. The two groups were similar with respect to age, sex, cold ischemia time, degree of sensitization, HLA matching, DR matching, and DR mismatching. The no CCB group did receive a significantly greater number of pretransplant transfusions. In the 1 year of follow-up, graft loss in the CCB group was less than in the no CCB group (1/17, 5.9% vs. 6/24, 25%). There was a striking decrease in the percentage of first rejection episodes in the CCB group as compared with no CCB therapy (35% vs. 83%, P less than 0.005). In addition, a similar decrease in second rejection episodes was found in the CCB group (18% vs. 33%, P less than 0.05). The two groups also were compared with respect to graft function. Despite similar serum creatinine levels at 1 month (CCB 1.8 mg% vs. no CCB 2.2 mg%, P = 0.37) and 1 year (CCB 1.7 mg% vs. no CCB 2.4 mg%, P = 0.19), the CCB group had a significantly higher glomerular filtration rate at 1 month (53.9 vs. 38.7, P less than 0.05) and 1 year (57.0 vs. 35.0, P less than 0.001) as measured by clearance of radiolabeled iothalamate. These results suggest that the short-term improvements noted in both graft function and rejection episodes with CCB are maintained for the first year posttransplant. More importantly, CCB use results in improved 1-year graft survival.

Adult↗

PubMed1991

Verapamil improves the outcome after cadaver renal transplantation.

Because of their favorable effects on renal hemodynamics, calcium antagonists may have a major role in the prevention and management of certain types of acute renal dysfunction. In fact, verapamil (VP) was shown to prevent cyclosporin A (CsA)-induced decreases in RBF in mice and in cadaver renal transplant (CRT) recipients. The study presented here of 59 cadaver renal transplant patients evaluates the outcome from perioperative treatment with VP (N = 30) administered intraoperatively into the renal artery (10 mg) followed by oral administration of 120 mg every 8 to 12 h for 14 days versus no drug (N = 29). Early immunosuppression included azathioprine, corticosteroids, and antilymphocyte globulin with subsequent overlapping with CsA on days 5 and 6. Actuarial graft survival at 1 yr was different when the two groups were compared (P less than 0.05). Estimated graft survival at 1 yr for VP patients was 93.3 compared with 72.4% in control patients. The improved graft survival was most striking in repeat transplants with 90% graft survival at 1 yr for VP recipients versus 37.5% for controls. Compared with controls, VP recipients had significantly improved renal parenchymal diastolic blood flow velocities on the first day after surgery (7.8 versus 5.8 cm/s). By day 7, GFR were greater with VP (44 +/- 29 mL/min) versus controls (28 +/- 22 mL/min). Of VP patients, 67% (18 of 24) had GFR greater than 30 mL/min versus 33% (9 of 26) for control patients. Similarly, on the seventh day, 77% (21 of 30) of VP patients had serum creatinines less than 2.0 mg% versus 34% (10 of 29) for controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Cardiac output and organ blood flow in experimental septic shock: effect of treatment with antibiotics, corticosteroids, and fluid infusion.

Septic shock from intraperitoneal (i.p.) injection of live Escherichia coli bacteria in rats induces marked pathophysiological changes, including 40% decrease in plasma volume (PV), cardiac output, and oxygen consumption with 100% mortality within 24 hr. The present study evaluates cardiac output and organ blood flow before and after treatment of septic shock with an effective antibiotic (AB), plasma volume (PV) expansion, and corticosteroids (CS), alone and in combination. Treatment was initiated at 5.5 hr after bacterial injection, at a time when AB therapy did not improve 24 hr survival rate. Cardiac output decreased from 28.6 +/- 3.1 (SD) to 15.4 +/- 2.8 ml/min/kg (P less than .01) in septic rats concomitant with redistribution of blood flow from carcass to the heart, brain, intestines, liver, and adrenal glands. Absolute arterial blood flow increased only to the adrenal glands and the liver to 158% (P less than .01) and 167% (P less than .01) of control values, respectively. AB, CS, and Ringer's lactate (RL) alone or in combination did not significantly improve any organ blood flow compared to untreated septic animals but increased survival significantly to about 60% (P less than .01). Albumin (ALB) and CS in combination expanded PV to 138% (P less than .01), restored cardiac output to 100%, and achieved supranormal blood flow values to the brain (109%), liver (125%), small intestine (147%) (P less than .01), and kidneys (190%) (P less than .01) of preshock levels. More importantly, survival at 24 hr was 90% (9/10) (P less than .001). It is concluded that a colloid diluted in an electrolyte solution, combined with CS, and an effective antibiotic agent are necessary therapeutic ingredients for the successful recovery of experimental E. coli sepsis.

Adrenal Cortex Hormones↗