Biomedical subjects

R Koren

Publications and source records attributed to R Koren.

At least 19 recordsLinked to original sources

PubMed2007

Enamel matrix derivative stimulates human gingival fibroblast proliferation via ERK.

Emdogain, a formulation of Enamel Matrix Proteins, is used clinically for periodontal regeneration to stimulate PDL (periodontal ligament), cementum, and bone formation. Its effects on gingival fibroblasts and tissue have not been thoroughly studied. Therefore, we investigated the mechanisms by which Emdogain affects the cell cycle of human gingival fibroblasts. Without serum, Emdogain (50 microg/mL) induced human gingival fibroblast entry into the S phase and DNA synthesis, but not completion of the cell cycle. With low serum concentrations (0.2-0.5%), Emdogain synergistically induced completion of the cell cycle, resulting in increased cell numbers. The mitogenic response to Emdogain depended on Extracellular Regulated Kinase (ERK) activation, which occurred in two waves, peaking after 15 min and 4 to 6 hrs, since it was abolished by U0126, a specific MAPK inhibitor. Inhibition of the second wave was sufficient to abrogate mitogenesis. This study characterized the mitogenic effect of Emdogain on primary human gingival fibroblasts, its cooperation with serum growth factors, and the key mediatory role of the ERK cascade.

Blood↗

PubMed2006

Programmed cell death of stressed keratinocytes and its inhibition by vitamin D: the role of death and survival signaling pathways.

The epidermis is confronted with multiple environmental and pathophysiological stresses. This study shows that TNFalpha, oxidative stress, hyperosmotic and heat shock induced both caspase-dependent and independent cell death in human HaCaT keratinocytes. The hormonal form of vitamin D, 1,25(OH)2D3, which is an autocrine hormone in the epidermis, protected the cells from all the examined stresses and pathways leading to cell death. We aimed to define the signaling pathways that determine the life-death balance of stressed keratinocytes and participate in their protection by 1,25(OH)2D3. As assessed by employing specific inhibitors, the survival pathways mediated by the EGF receptor, ERK, PI-3K or Src kinase, or basal transcriptional activity are important for unstressed cell survival. However, only the EGF receptor, PI-3K and the Src kinase pathways mediate the survival of stressed cells in a stimulus-specific manner. Inhibition of the p38 and/or the JNK death pathways reduced caspase activation induced by oxidative stress, hyperosmotic shock and TNFalpha. The protective effect of 1,25(OH)2D3 was not mediated by the examined survival pathways. 1,25(OH)2D3 inhibited the stress-induced activation of p38 and JNK. Since mimicking this effect by pharmacological inhibition resulted in the attenuation of caspase activation, we infer that these pathways are involved in keratinocyte protection by 1,25(OH)2D3.

Apoptosis↗

PubMed2005

13C-urea breath test for success of Helicobacter pylori eradication: study of 5885 Israeli patients.

Helicobacter pylori (Hp) infection is highly prevalent in many countries and may cause gastritis, peptic ulcer disease, gastric cancer, and lymphoma. Successful eradication depends on the specific treatment used, patient compliance, and Hp antibiotic resistance. The primary aim was to characterize groups of patients with one or more failures of Hp eradication treatment. The secondary aim was to evaluate the factors that influence eradication failure. Between April 1, 1998, and December 31, 2001, 5885 patients were studied for the success of Hp eradication with the 13C-urea breath test (13C-UBT): 5442 after one course of treatment (Group I), 380 after two courses (Group II), and 63 after three courses (Group III). The 13C-UBT was positive in 27.8%, 37.4%, and 47.6% of patients in Groups I, II, and III, respectively (P(I-II) = 0.000, P(II-III) = 0.126). A combination of omeprazole, amoxicillin, and clarithromycin (OAC) was used in 31.3%, 27.4%, and 7.9% of Groups I, II, and III, respectively, and a combination of omeprazole, amoxicillin, and metronidazole (OAM) in 15.2%, 28.9%, and 28.6%, respectively. Regimens that contained clarithromycin were used in decreasing order in Groups I, II, and III, and regimens containing metronidazole, bismuth, or tetracycline, in increasing order. The only good prognostic factor for successful eradication was Israeli origin, while European-American and Asian-African origin, recurrence of symptoms, a history of duodenal ulcer, and chronic proton pump inhibitor (PPI) use did not favor successful eradication. Our results suggest that origin, history of peptic disease, and chronic PPI use are predictors of eradication failure.

Adolescent↗

PubMed2005

An ancillary tool for the diagnosis of amyloid A amyloidosis in a variety of domestic and wild animals.

Immunohistochemistry, the standard method for diagnosing amyloid A (AA) amyloidosis, is limited in animals because it requires a large array of animal-specific anti-AA antibodies, not commercially available. The Shtrasburg method (SH method) is a highly specific and sensitive technique, helping in the diagnosis and determination of AA amyloidosis in humans. The aim of this study is to determine whether the SH method is applicable in the diagnosis of AA amyloidosis in a variety of animals. Tissue samples were obtained from animals suffering from spontaneous or experimentally induced AA amyloidosis (mice, hamsters, guinea pigs, cheetahs, cats, cows, ducks, a dog, a goose, a chicken, and a turaco). Detection of the amyloid and quantitative evaluation were performed using Congo red staining, and specific AA typing was performed by the potassium permanganate technique. The studied tissues were subjected to the SH method, which confirmed the AA nature of the amyloid deposit, by displaying in polyacrylamide gel electrophoresis protein bands consistent with the molecular weight of the species-specific AA, in all the animals examined, except mice, hamsters, and guinea pigs. N-terminal analysis of these bands corroborated their AA origin. We conclude that the SH method may be used as an ancillary simple tool for the diagnosis of AA amyloidosis in a large number of domestic and wild animals. Moreover, our findings further increase the feasibility of applying this method in humans.

Acinonyx↗

PubMed2004

Trichloroacetic acid cycling in Sitka spruce saplings and effects on sapling health following long term exposure.

Trichloroacetic acid (TCA, CCl(3)COOH) has been associated with forest damage but the source of TCA to trees is poorly characterised. To investigate the routes and effects of TCA uptake in conifers, 120 Sitka spruce (Picea sitchensis (Bong.) Carr) saplings were exposed to control, 10 or 100 microg l(-1) solutions of TCA applied twice weekly to foliage only or soil only over two consecutive 5-month growing seasons. At the end of each growing season similar elevated TCA concentrations (approximate range 200-300 ng g(-1) dwt) were detected in both foliage and soil-dosed saplings exposed to 100 microg l(-1) TCA solutions showing that TCA uptake can occur from both exposure routes. Higher TCA concentrations in branchwood of foliage-dosed saplings suggest that atmospheric TCA in solution is taken up indirectly into conifer needles via branch and stemwood. TCA concentrations in needles declined slowly by only 25-30% over 6 months of winter without dosing. No effect of TCA exposure on sapling growth was measured during the experiment. However at the end of the first growing season needles of saplings exposed to 10 or 100 microg l(-1) foliage-applied TCA showed significantly more visible damage, higher activities of some detoxifying enzymes, lower protein contents and poorer water control than needles of saplings dosed with the same TCA concentrations to the soil. At the end of each growing season the combined TCA storage in needles, stemwood, branchwood and soil of each sapling was <6% of TCA applied. Even with an estimated half-life of tens of days for within-sapling elimination of TCA during the growing season, this indicates that TCA is eliminated rapidly before uptake or accumulates in another compartment. Although TCA stored in sapling needles accounted for only a small proportion of TCA stored in the sapling/soil system it appears to significantly affect some measures of sapling health.

Air Pollutants↗

PubMed2004

DCC protein expression in clear cell renal cell carcinoma.

OBJECTIVES: To investigate whether the expression of protein from the "deleted in colorectal cancer" (DCC) gene, which predicts a poor outcome for patients with colorectal carcinoma, can also serve as a prognostic factor in renal cell carcinoma (RCC). PATIENTS AND METHODS: The expression of DCC was evaluated immunohistochemically in 94 paraffin-embedded tumour samples from patients with stage T1, T2, and T3 clear cell RCC. The mean follow-up was 52.3 months. The endpoints of the study were recurrence of disease and death from disease. RESULTS: The under-expression of DCC protein was detected in 63% of patients who died from the disease and in 36% with no evidence of disease. DCC protein under-expression was detected in all patients with T1 tumours who died from the disease, in half the T2 tumours and in two-thirds of T3 tumours. CONCLUSION: DCC protein under-expression correlated with more aggressive tumour behaviour and a greater risk of death from RCC. However, a larger cohort of patients should be assessed before drawing definitive conclusions.

Adult↗

PubMed2003

Human DNA topoisomerase-IIalpha expression as a prognostic factor for transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To investigate the immunohistochemical expression of topoisomerase II-alpha (TII-alpha, a nuclear enzyme, the expression of which increases rapidly at the end of the S to G2/M phase and declines when mitosis ends) in bladder urothelial neoplasms (transitional cell carcinoma), and its correlation with grade, stage and survival. PATIENTS AND METHODS: Histological sections from 57 urothelial neoplasms were stained immunohistochemically for TII-alpha expression; the percentage of positive cells in the area of greatest staining was recorded as the TII-alpha index. RESULTS: TII-alpha nuclear staining was positive in all the samples except one. The mean (sd) TII-alpha index was 10.7 (5.9) in urothelial neoplasms of low malignant potential (grade 1), 15.5 (5.0) in low-grade (grade 2) and 42.1 (13.4) in high-grade urothelial carcinoma (grade 3). The mean TII-alpha index was 10.7 (5.9), 26.3 (14.8) and 44 (19) in stages pTa, pT1 and pT2, respectively. The TII-alpha index was significant for predicting death from cancer, independently of the stage or grade of the disease (P = 0.019, hazard ratio 1.1). CONCLUSIONS: A higher TII-alpha index indicates a greater probability of recurrence of disease and lower overall survival. Therefore TII-alpha expression has prognostic value in bladder carcinoma.

Adult↗

PubMed2003

Photon undulatory non-linear conversion diagnostic method for caries detection: a pilot study.

OBJECTIVE: The objective of this study was to evaluate a new optical method - photon undulatory non-linear conversion (PNC)--for use in different stages of caries detection. BACKGROUND DATA: Caries should be considered an infectious disease managed by risk assessment, early detection, and preventive therapies, rather than simply "drilling and filling." MATERIAL AND METHODS: Fluorescence emission spectroscopy was performed in vitro on 90 extracted teeth, with intact occlusal surfaces. This system differs from the basic Diagnodent unit in its ability to distinguish between different tissue components with respect to their spectrums. Histological analysis served as the gold standard for verification. The teeth sections correspond to the specific point with the highest reading of the detector. The system was compared to visual inspection, probing, and x-ray methods. The system tested (helium-neon [He-Ne], lambda = 633 nm) has a fiber optic device that delivers radiation to the tooth and a spectrophotometer device that detects bacterial porphyrins fluorescence, allowing detection of caries, fillings, and calculus by simultaneous measurement of backscattering and fluorescence intensity. RESULTS: The system tested provides quantitatively reproducible measurements and detection even through sound enamel of more than 1 mm in thickness. CONCLUSION: The PNC method detects different stages of caries lesions in real time, and it exceeds x-rays in sensitivity, without any ionizing radiation. Preliminary results showed a high potential of using the PNC method in clinical practice (98% accuracy) in comparison to the other methods.

Dental Caries↗

PubMed2003

Vitamin D enhances caspase-dependent and independent TNF-induced breast cancer cell death: the role of reactive oxygen species.

Calcitriol, the hormonal form of vitamin D, enhanced TNF-induced cytotoxicity in MCF-7 breast cancer cells. It increased the induction of caspase-3-like activity and TNF-induced caspase-independent cytotoxicity in the presence of a pan-caspase inhibitor. The antioxidants N-acetylcysteine, glutathione, lipoic acid, and ascorbic acid markedly reduced the effect of the hormone on TNF-induced caspase activation, attesting to the involvement of reactive oxygen species (ROS) in the cross-talk between the hormone and the cytokine. Calcitriol augmented the drop in mitochondrial membrane potential induced by TNF as assessed by the fluorescent probe JC-1. We postulate that the interaction of TNF and calcitriol on the level of the mitochondria underlies the enhancement of TNF-induced, ROS-mediated caspase-dependent and -independent cell death.

Antioxidants↗

PubMed2003

Laser posterior ventriculocordectomy with partial arytenoidectomy for the treatment of bilateral vocal fold immobility.

Bilateral vocal fold immobility in adduction usually creates severe dyspnoea. Many surgical procedures have been established to improve the airway insufficiency in affected patients. Over the last six years 22 patients with bilateral vocal fold immobility in our department have undergone CO(2) laser posterior ventriculocordectomy with partial arytenoidectomy (PVCPA). None had dyspnoea or a disturbance in the immediate post-operative period or during follow up, which ranged from five months to six years. Only one patient required a second procedure. Laser PVCPA appears to be an effective and reliable method for the treatment of bilateral vocal fold immobility in selected patients.

Adolescent↗

PubMed2002

Association between gastric acid and mucin secretion in dyspeptic patients.

BACKGROUND AND AIMS: The maintenance of an intact gastric mucosa implies a balance between aggressive, such as acid, and protective factors such as mucin. We examined gastric aspirates to determine a possible correlation between gastric acid and mucin contents. METHODS: Gastric contents were aspirated at gastroscopy in 14 patients. Acid content was evaluated by titration, and mucin content by gel filtration. In 4 other patients these measurements were also performed for 1-hour basal gastric secretion, and after pentagastrin stimulation. Western blot and dot blot for mucin protein were performed with polyclonal antibodies to the protein of MUC 5AC and MUC 6. RESULTS: A positive correlation was demonstrated between acid and mucin content in 14 patients, r = 0.77. In 4 other patients mucin secretion, after pentagastrin injection, increased by 3-46 fold in comparison with basal secretion. A positive correlation was demonstrated between basal acid and mucin secretion, and stimulated acid and mucin secretion. In dot blot experiments, MUC 5AC had a significant higher dot blot intensity than MUC 6. CONCLUSIONS: There is a correlation between acid and mucin secretion rates. Secretagogue that causes acid secretion may also cause secretion of protective mucin.

Aged↗

PubMed2002

Vitamin D inhibits the activation of stress-activated protein kinases by physiological and environmental stresses in keratinocytes.

In addition to its known effects on keratinocyte proliferation and differentiation, the hormonal form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has been shown to protect keratinocytes from UV- and chemotherapy-induced damage. Epidermal keratinocytes contain both the machinery needed to produce 1,25(OH)(2)D(3) and vitamin D receptors. The activation of the stress-activated protein kinases (SAPKs), such as c-Jun N-terminal kinase (JNK) and p38, is an early cellular response to stress signals and an important determinant of cell fate. This study examines whether modulation of these SAPKs is associated with the effects of 1,25(OH)(2)D(3) on keratinocytes under stress. HaCaT keratinocytes were exposed to heat shock, hyperosmotic concentrations of sorbitol, the epidermal growth factor receptor tyrosine kinase inhibitor AG1487, the pro-inflammatory cytokine tumor necrosis factor alpha, and H(2)O(2). These stresses activated both SAPKs. Pretreatment with 1,25(OH)(2)D(3) inhibited the activation of JNK by all stresses and the activation of p38 by heat shock, AG1478 and tumor necrosis factor alpha. Under the same conditions, treatment with 1,25(OH)(2)D(3) protected HaCaT keratinocytes from cytotoxicity induced by exposure to H(2)O(2) and hyperosmotic shock. The effect of 1,25(OH)(2)D(3) was dose-dependent, already apparent at nanomolar concentrations, and time-dependent, maximal after a 24-h pre-incubation. We suggest that inhibition of SAPK activation may account for some of the well-documented protective effects of 1,25(OH)(2)D(3) on epidermal cells during exposure to UV or chemotherapy and may also be related to the anti-inflammatory actions of the hormone in skin.

Calcitriol↗

PubMed2001

Vitamin D is a prooxidant in breast cancer cells.

The anticancer activity of the hormonal form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D], is associated with inhibition of cell cycle progression, induction of differentiation, and apoptosis. In addition, 1,25(OH)2D3 augments the activity of anticancer agents that induce excessive reactive oxygen species generation in their target cells. This study aimed to find out whether 1,25(OH)2D3, acting as a single agent, is a prooxidant in cancer cells. The ratio between oxidized and reduced glulathione and the oxidation-dependent inactivation of glyceraldehyde-3phosphate dehydrogenase (GAPDH) are considered independent markers of cellular reactive oxygen species homeostasis and redox state. Treatment of MCF-7 breast cancer cells with 1,25(OH)2D3 (10-100 nM for 24-48 h) brought about a maximal increase of 41+/-13% (mean +/- SE) in the oxidized/reduced glutathione ratio without affecting total glutathione levels. The in situ activity of glutathione peroxidase and catalase were not affected by 1,25(OH)2D3, as assessed by the rate of H2O2 degradation by MCF-7 cell cultures. Neither did treatment with 1,25(OH)2D3 affect the levels of glutathione reductase or glutathione S-transferase as assayed in cell extracts. The hormone did not affect overall glutathione consumption and efflux as reflected in the rate of decline of total cellular glutathione after inhibition of its synthesis by buthionine sulfoximine. The extent of reversible oxidation-dependent inactivation of GAPDH in situ was determined by comparing the enzyme activity before and after reduction of cell extracts with DTT. The oxidized fraction was 0.13+/-0.02 of total GAPDH in control cultures and increased by 56+/-5.3% after treatment with 1,25(OH)2D3, which did not affect the total reduced enzyme activity. Treatment with 1,25(OH)2D3 resulted in a approximately 40% increase in glucose-6-phosphate dehydrogenase, the rate-limiting enzyme in the generation of NADPH. This enzyme is induced in response to various modes of oxidative challenge in mammalian cells. Taken together, these findings indicate that 1,25(OH)2D3 causes an increase in the overall cellular redox potential that could translate into modulation of redox-sensitive enzymes and transcription factors that regulate cell cycle progression, differentiation, and apoptosis.

Antimetabolites↗

PubMed2001

Increased incidence of diabetes mellitus in the patients with transitional cell carcinoma of urinary bladder.

The progression of bladder cancer to invasive disease is highly dependent on its ability to penetrate basement membrane of urothelium. Studies on diabetic nephropathy have shown a reduction in proteoglycan content of the glomerular basement membrane. Based on the well-known fact that proteoglycans are one of the main components of basement membrane and extracellular matrix we assessed the relationship between diabetes mellitus, bladder cancer incidence and its behavior. These studies include 252 patients with microscopically confirmed transitional cell carcinoma of bladder, and 549 patients with other urological disorders who served as controls. The prevalence of diabetes mellitus in each group was assessed. The group of patients suffering from transitional cell carcinoma was divided according to etiological risk factors such as cigarette smoking, diabetes and patients that were non-smokers and did not suffer from diabetes mellitus. We assessed the features of bladder cancer behavior in each group. Logistic regression model estimation for statistical analysis was used, with transitional cell carcinoma as a dependent binary variable and age, sexes smoking and diabetes as independent variables. Statistical significance was considered at two levels: p <or=0.001 and p <or=0.05. Odds ratio (OR) adjusted to age, sex, cigarette smoking, diabetes mellitus and 95% Confidence Interval (CI) were calculated for TCC. In the TCC group 22.2% of the patients suffered from diabetes mellitus. In the control group 10.38% suffered from diabetes mellitus. Logistic regression analysis, OR and 95% CI showed a statistically significant relationship between diabetes and TCC. These data are comparable only with smoking (OR 2.3; 95% CI 1.6 3.5 and OR 1.58; 95% CI 1.08 2.4 correspondingly). Based on these data we suggest that diabetes mellitus may be considered an etiological risk factor for bladder cancer development.

Adult↗

PubMed2001

99mTc-MIBI scintigraphy of parathyroid adenomas and its relation to tumour size and oxyphil cell abundance.

The aim of this study was to assess the correlation between technetium-99m methoxyisobutylisonitrile (MIBI) uptake by parathyroid adenomas, oxyphil cell content and volume of the lesions. Thirty-one patients with parathyroid adenomas were evaluated prospectively. Preoperative double-phase 99mTc-MIBI scintigraphy was performed in all patients and tracer uptake by parathyroid lesions was assessed semi-quantitatively employing region of interest ratios to normal adjacent neck areas. Surgical specimens underwent histological evaluation and oxyphil cell content was determined. The intensity of tracer uptake was compared with oxyphil cell content, volume of the lesions and serum levels of calcium and parathormone. 99mTc-MIBI tracer uptake was correlated with oxyphil cell content, volume of parathyroid lesions and the functional status of the parathyroid adenomas. Tracer accumulation in oxyphil cells might partially explain the preferential 99mTc-MIBI retention in parathyroid lesions.

Adenoma↗

PubMed2001

Effects of senescence and citral on neuronal vacuolar degeneration in rat pelvic ganglia.

A significant part of the morbidity in elderly men involves pelvic organs and their autonomic neural regulation. Environmental stimuli also impair the structure and function of pelvic organs. One of these factors is citral, a widely-used cosmetic fragrance constituent, which causes severe prostatic hyperplasia in rats. In this study, we assessed the effect of topical administration of citral (30 days) on the morphology of pelvic ganglia (PG) in young adult and old Wistar rats. Neuronal vacuolar degeneration with preserved nuclei of PG neurons was observed in untreated senescent, but not young rats. Citral significantly increased the rate of vacuolated neurons in old rats (from 3 to 14%), but only slightly in young ones (from 0 to 0.5-0.3%). Similar lesions were not found in inferior cervical or celiac ganglia, in either group. This shows that environmental stimuli enhance age-related processes of vacuolar neuronal degeneration in PG, and may contribute to the dysfunction of pelvic organs in the elderly.

Acyclic Monoterpenes↗

PubMed2001

Neck-dissection surgical specimens treated by lymph node revealing solution.

The detection of metastatic lymph nodes in cancer patients is essential for determining the cancer stage, and thus, the therapeutic modalities. However, very small lymph nodes can easily be missed during routine examination. We described a "Lymph Node Revealing Solution" (LNRS) that helps to detect tiny lymph nodes in neck dissection specimens. Twenty-one consecutive specimens of neck-dissection were investigated. The entire surgical specimen, fixed at first in formalin, was searched for lymph nodes by the traditional method. These were excised and sent for processing. The remaining tissue was immersed for 24 hours in LNRS. The lymph nodes stood out as white chalky nodules on the background of the yellow fat. They were then excised, and examined. A total of 227 lymph nodes were detected by the traditional method; 38 (17%) were positive for metastasis. Using the LNRS method, an additional 72 nodes were identified, among them 8 (11%) were positive for metastases and 2 cases were upstaged. LNRS is an inexpensive and easy method of detecting tiny lymph nodes; it enhances significantly the yield of normal and metastatic nodes of neck-dissection specimens and helps to establish a more accurate staging.

Carcinoma, Squamous Cell↗

PubMed2001

Capsular collagen staining of follicular thyroid neoplasms by picrosirius red: role in differential diagnosis.

A key criterion in the diagnosis of thyroid follicular carcinoma is capsular invasion, but invasion cannot always be demonstrated histologically. Since invasion is likely to evoke reactions in the capsular collagen, we examined the effects of invasion on capsular collagen with the picrosirius orange-red (PSR) staining technique for collagen. Under polarized light, the color of PSR-stained collagen varies as a function of the structural and biochemical properties of the collagen fibers. Capsules of widely invasive carcinomas (n = 10), minimally invasive carcinomas (n = 10), and adenomas (n = 28) were stained with the PSR method. Carcinomas were assessed along the thickened capsule for sites of definite invasion, minimal invasion, and no evidence of invasion. In adenomas, sites of thickened capsules (similar to carcinomas) were compared to sites of thin capsules. All foci were evaluated for the color and color intensity of collagen fibers. We found a significantly higher frequency of yellow-green collagen fibers than of orange-red fibers at sites of invasion, whereas orange-red fibers significantly predominated at non-invaded sites. In a minority of cases both colors occurred but the non-dominant color was of lesser intensity in all but 1 case. There were no significant differences in staining between minimally and widely invasive carcinomas. Thick capsules of adenomas consistently stained with an intense orange-red color, although weakly stained yellow-green fibers were also observed in some of these cases. We conclude that PSR staining can provide diagnostically useful information in capsular samples of carcinomas, when both color and color intensity of PSR staining are evaluated at the same site. Specifically, intense yellow-green birefringence of collagen in a thickened capsule is additional evidence for capsular invasion.

Adenoma↗