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Biomedical subjects

J Toth

Publications and source records attributed to J Toth.

At least 19 recordsLinked to original sources
PubMed2004

[Drug therapy for disturbances of smelling].

Disorders of the sense of smell are frequent. This severely can affect the quality of live. Appropriate testing is needed to determine the nature of the patient's complaints. Following the pathogenesis, two main groups of smell disorders are discernable: The conductive-respiratory smell disorders, where the odour can not reach the receptor and the senso-neuronal disorders where perception or transduction is affected. Therefore two different therapeutical approaches are described.

Adrenal Cortex Hormones↗
PubMed2004

Phosphorus concentration and solubility in dairy feces: variability and affecting factors.

Recent data from phosphorus (P) feeding trials have demonstrated that P concentration in dairy feces is directly affected by P levels in diets and that farm P surpluses as well as potential environmental losses can be reduced through dietary manipulation. The current study was conducted to examine the variability of fecal P under farm conditions and to elucidate factors affecting the concentration and solubility of fecal P. Feed and fecal samples from >30 commercial dairies in the Northeast and Mid-Atlantic regions were analyzed. Dietary P concentrations ranged from 3.45 to 5.78 g/kg of feed DM (DM), and P determined in acid digests (TP) of feces from 5.84 to 12.84 g/kg of fecal DM. On average, 50% of fecal TP was water soluble; of the latter, 83% was inorganic (Pi). Across-farm variability (n=33) had CV averaging 18.9% for fecal TP and >20% for Pi and total P (Pt) in water extracts. Within-farm variability based on multiple samples per herd had the same magnitude as across-farm and was independent of sample numbers from individual farms (n=7 to 30). Of all fecal parameters determined, pH and DM had the lowest variability (CV <10%), water-soluble Pi, Pt, and Ca the highest (CV of 20 to 30%), and total P, Ca, and Mg determined by acid digests were intermediate (CV 10 to 20%). Water-soluble Pi concentrations determined in dried-ground fecal samples were lower than in wet samples. The drying-grinding process changes Pi solubility and the change is not linear. This study confirms that dietary P concentration is the dominating factor affecting fecal P excretion; however, Ca concentration, DIM, and fecal pH also made small, but statistically significant contributions, although some of the mechanisms remain to be thoroughly investigated.

Animal Feed↗
PubMed2002

A two step model aimed at delivering antisense oligonucleotides in targeted cells.

To be efficient in vivo antisense oligonucleotides must reach the targeted cells and then cross the cellular membrane. We propose a two step system where the oligonucleotide is first electrostatically bound to a peptide coupled to a ligand of a cellular receptor. A complex is formed which allows the oligonucleotide to be bound to the membrane of the targeted cells. These oligonucleotides are then delivered inside the cells by the subsequent use of a transfection agent. As a reductionist model of peptide coupled to a ligand we have used a lipopeptide and characterized by a filter elution assay the stoichiometry between the peptide and the oligonucleotide in the complexes. Using HeLa cultured cells we have shown that addition of these complexes to the cells triggers the oligonucleotide binding to the cell membrane. The subsequent addition of dendrimers allows these antisense oligonucleotides to inhibit a reporter gene inside the cells.

Base Sequence↗
PubMed2001

Crystal structure of an ephrin ectodomain.

Eph receptor tyrosine kinases and their membrane-associated ligands, the ephrins, are essential regulators of axon guidance, cell migration, segmentation, and angiogenesis. There are two classes of vertebrate ephrin ligands which have distinct binding specificities for their cognate receptors. Multimerization of the ligands is required for receptor activation, and ephrin ligands themselves signal intracellularly upon binding Eph receptors. We have determined the structure of the extracellular domain of mouse ephrin-B2. The ephrin ectodomain is an eight-stranded beta barrel with topological similarity to plant nodulins and phytocyanins. Based on the structure, we have identified potential surface determinants of Eph/ephrin binding specificity and a ligand dimerization region. The high sequence similarity among ephrin ectodomains indicates that all ephrins may be modeled upon the ephrin-B2 structure presented here.

Amino Acid Sequence↗
PubMed2001

Nitrogen-fixation genes and nitrogenase activity in Clostridium acetobutylicum and Clostridium beijerinckii.

Several solvent-producing clostridia, including Clostridium acetobutylicum and C. beijerinckii, were previously shown to be nitrogen-fixing organisms based on the incorporation of 15N2 into cellular material. The key nitrogen-fixation (nif) genes, including nifH, nifD, and nifK for nitrogenase component proteins as well as nifE, nifN, nifB and nifV for synthesis of the iron-molybdenum cofactor (FeMoco) of nitrogenase, have now been identified in C. acetobutylicum or C. beijerinckii or both. The organization of these genes is similar to the distinctive pattern that was first observed in Clostridium pasteurianum, with the nifN and nifB genes fused into the nifN-B gene and with the nifV gene split into the nifVomega and nifValpha genes. The corresponding nif genes of these three clostridial species are highly related to each other. However, in the two solvent-producing clostridia, the nifH and nifD genes are interspersed by two glnB-like genes, which are absent in the corresponding region in C. pasteurianum. However, the nifN-B and nifVomega genes of C. pasteurianum are interspersed by the putative modA and modB genes (for molybdate transport), which are absent in the corresponding region in C. acetobutylicum. C. acetobutylicum and C. beijerinckii grew well under nitrogen-fixing conditions, and the acetylene-reducing activity of nitrogenase was measured in the two species. Acetone, butanol, and isopropanol production occurred in nitrogen-fixing cultures, but the peak of nitrogen-fixing activity preceded the active solventogenic phase.

Acetylene↗
PubMed2001

Efficacy and safety of an oral formulation of cetirizine and prolonged-release pseudoephedrine versus xylometazoline nasal spray in nasal congestion.

The aim of this study was to compare the decongestant properties and tolerability of the sympathomimetic xylometazoline hydrochloride 0.1% (CAS 1218-35-5, XMZ) and an oral formulation of cetirizine hydrochloride 5 mg and pseudoephedrine hydrochloride 120 mg (CAS 83881-51-0 and 90-82-4, CTZ/PSE; Cirrus). Thirty-six asymptomatic patients suffering from perennial allergic rhinitis from house dust mite were randomized to this open two-period crossover study. Patients received the study medications for four days each. In each period, treatments were taken twice a day. On day 1 in each period, immediately after the first dose of medication, patients were challenged with Dermatophagoides pteronyssinus extract 1 in the Vienna Challenge Chamber for 5 h. Primary efficacy parameters were nasal congestion evaluated by digital analysis of nasal cavity photographs and nasal airflow. Furthermore amounts of nasal secretions, nasal and ocular symptoms were recorded. In addition, 5 independent Ear-Nose-Throat specialists also assessed nasal cavity photographs. Statistical analyses were conducted at the 5% level of significance. Digital analysis of the nasal cavity photographs as well as nasal airflow measurements did not differentiate XMZ from CTZ/PSE. Ratings of the photographs of the nasal cavity emphasized the rapid onset of XMZ. No clinically relevant adverse events were recorded. This rapid onset of action but short-lived effect of topical xylometazoline 0.1% should be balanced against the consistent and prolonged effect of systemic cetirizine/pseudoephedrine combination in the treatment of perennial allergic rhinitis as no significant differences between these 2 medications were noted regarding their decongestant properties. With the exception of nasal obstruction, all subjective symptoms as well as the global condition were significantly better under CTZ/PSE. Amounts of nasal secretions during these sessions were significantly lower with CTZ/PSE.

Administration, Intranasal↗
PubMed2000

Upper airway findings in patients with nocturnal breathing disorders.

This prospective open study was performed to examine the relation between pathologic findings of the upper respiratory tract and the types of noncentral sleep disorders (rhonchopathy, obstructive sleep apnea). 312 men and 274 women aged between 35-75 years attended our outpatient department for relief of their nocturnal breathing disorder. About 1/3 of the patients suffered only of habitual rhonchopathy and 2/3 were obstructive. No findings of the head and neck examination could predict the degree of oxygen desaturation, although pathologies of the nose (73.68%), the soft palate (94.1%) and narrowing of the oro- and hypopharynx (74.19%) were very common in patients with sleep disorder. At least one pathology could be found in every patients. The more pathologies were found the higher was the risk of obstructive sleep apnoea with desaturation below 70%. Unrelated tonsillectomy (51.36%) did not prevent nocturnal breathing disorders.

Adult↗
PubMed2000

Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary.

We have investigated the impact of BRCA1 and BRCA2 mutations that were frequently identified among Hungarian high-risk breast-ovarian cancer families (Ramus et al., 1997b, AJHG), on the development of breast and ovarian cancer in the general Hungarian population. The prevalence of 3 BRCA1 mutations (185delAG, 300T-->G and 5382insC) and 2 BRCA2 mutations (6174delT and 9326insA) was evaluated in a hospital-based consecutive series of 500 female breast cancer patients and 90 ovarian cancer patients, not selected for age at diagnosis or family history of cancer, as well as in 350 controls. Among breast cancer patients, 3.6% (18/500) carried a founder mutation: 9 BRCA1 300T-->G, 7 BRCA1 5382insC, 1 BRCA1 185delAG and 1 BRCA2 9326insA. Among ovarian cancer patients, 11% (10/90) carried a founder mutation: 5 BRCA1 185delAG, 4 BRCA1 300T-->G and 1 BRCA1 5382insC. One control carried a mutation, BRCA1 5382insC. Inherited breast cancer was more frequent among women with younger age at diagnosis: 6.1% of women younger than age 50 but 2.4% of women diagnosed at age 50 or older carried one of the founder mutations. There was no association between mutation status and age at diagnosis of ovarian cancer. Three of 23 medullary breast cancers were inherited (p = 0.038). Carrier status was also associated with a non-significant trend toward advanced tumor stage at diagnosis. These mutations could be evaluated among all ovarian cancer patients and breast cancer patients younger than age 60 and of Hungarian ancestry.

Age of Onset↗
PubMed2000

The specificity of protein-DNA crosslinking by formaldehyde: in vitro and in drosophila embryos.

Formaldehyde crosslinking has been widely used to study binding of specific proteins to DNA elements in intact cells. However, previous studies have not determined if this crosslinker preserves the bona fide pattern of DNA binding. Here we show that formaldehyde crosslinking of Drosophila embryos maps an interaction of the transcription factor Zeste to a known target element in the Ultrabithorax promoter. This data agrees broadly with previous mapping of the same Zeste binding sites by in vivo UV crosslinking, though the formaldehyde method does give a low, possibly artifactual signal on other DNA fragments that is not detected by the UV method. We also demonstrate, using an in vitro assay, that formaldehyde crosslinking accurately reflects the DNA binding specificities of both Zeste and a second transcription factor, Eve. The crosslinking reagent methylene blue is shown to preserve DNA binding specificity in vitro as well. Our results suggest that crosslinking by formaldehyde, and possibly also by methylene blue, provide an accurate guide to the interaction of proteins with their high affinity target sites in cells.

Animals↗
PubMed2000

Relation between p53 overexpression and clinical behavior of ocular/orbital invasion of conjunctival squamous cell carcinoma.

PURPOSE: To investigate the p53 gene as a prognostic indicator in conjunctival squamous cell carcinoma. METHODS: Medical records were reviewed and histopathology slides were examined to verify the diagnosis and grade of tumor differentiation in a retrospective case series of 12 patients with "invasive" and 11 patients with "noninvasive" conjunctival squamous cell carcinoma. The p53 antigen was detected using the streptavidin biotin-alkaline phosphatase immunostaining method. Statistical analysis was performed using the Fisher exact test. RESULTS: p53 overexpression was present in 14 cases (approximately 60%). Eight and 6 of 14 p53-positive tumors were invasive and noninvasive, respectively. All patients with recurrence (two), recurrence and metastasis (two), metastasis (three), and death with tumor dissemination (three) had p53 overexpression. Of all adverse outcomes, only two cases with recurrence were p53 negative: no metastasis or death with dissemination was seen in p53-negative tumor cases. CONCLUSIONS: There was no statistical relationship between p53 overexpression and age, sex, location, invasiveness, or histopathologic differentiation of the tumor; however, a significant association existed between p53 positivity and adverse clinical behavior (p = 0.014).

Aged↗
PubMed2000

The relationship between human papillomavirus and p53 gene in conjunctival squamous cell carcinoma.

PURPOSE: The p53 tumor-suppressor gene has been documented to exist in mutated forms in many types of squamous cell carcinoma in the body. Also in conjunctival squamous cell carcinoma, human papillomavirus (HPV) is accepted as an oncogenic factor. The objective of our study was to establish a correlation between p53 overexpression and the presence of HPV infection within tumor tissues from patients with conjunctival squamous cell carcinoma. METHODS: Tissue sections obtained from paraffin-embedded conjunctival squamous cell carcinoma specimens from 23 patients were examined with light microscopy, polymerase chain reaction (PCR), and immunohistochemistry. RESULTS: Seventy-eight percent of tumors were positive for p53, whereas 22% were positive for HPV. The proportion of patients positive for both p53 and HPV was 17%, whereas another 17% of the patients were negative for both p53 and HPV. Therefore no significant disproportion was found in the distribution of patients' HPV status and p53 status (p = 1.00). No significant correlation or linear association was found between the HPV status and p53 status (r = 0.022; p = 0.920). CONCLUSION: We could not show any statistical association between abnormal p53 gene-product expression by immunohistochemistry in conjunctival squamous cell carcinomas and HPV infection by PCR detection techniques.

Antibodies, Neoplasm↗
PubMed2000

Graves' ophthalmopathy: eye muscle involvement in patients with diplopia.

BACKGROUND: Diplopia identifies patients with eye muscle involvement in Graves' ophthalmopathy (GO). OBJECTIVE: To identify clinical parameters that could eliminate the need for magnetic resonance imaging (MRI) to assess the activity of inflammation in the eye muscles of GO patients with diplopia. METHODS: In 43 patients with GO with recently developed diplopia, orbital ultrasound and MRI were performed. Muscle diameters and MRI T2 relaxation times were measured, and the amount of orbital connective tissue was calculated from MRI scans and compared with ultrasound readings, diplopia grades, degree of protrusion, ocular pressure, tear production, antibody levels and hormonal parameters of thyroid function. RESULTS: No correlation was found between diameters of 233 extraocular muscles measured by MRI and by ultrasound. For each of the four muscles, there was a diameter above which ultrasound was always unreliable. MRI data were used in further analysis. Of the muscles examined, the inferior rectuses were the most frequently enlarged - at least one, in 93% of cases. Medial, lateral and superior rectuses were enlarged in 59%, 37% and 34% of the orbits respectively. The pattern of muscle involvement of the two orbits tended to be symmetric (r=0.49, P=0.003), particularly for the medial rectuses (r=0.90, P=0.000). Proptosis correlated with the sum of the muscle diameters for a given eye (right eye: r=0.54, P=0.003; left eye: r=0.57, P=0.001), but it failed to correlate with the amount of orbital connective tissue. In 53% of the patients, normal T2 relaxation times were found in all eight muscles. There was only a weak correlation between muscle thickness and T2 relaxation time (r=0.49, P=0.003), indicating that muscle enlargement alone is not a sign of disease activity. The severity of diplopia was independent of T2 relaxation time. The amount of orbital connective tissue showed a negative correlation with the greatest T2 relaxation time for a given eye (r= -0.52, P=0.004); this suggests that disease types exist that have predominant muscle involvement and predominant connective tissue expansion. No correlation between connective tissue expansion and proptosis, diplopia grade, muscle thickness or disease duration was found - that is, connective tissue expansion is not a major factor in diplopia. Both muscle and connective tissue findings were independent of thyroid function. CONCLUSION: Ultrasound and MRI eye muscle diameter readings do not correlate, because of the inherent inaccuracy of orbital ultrasound. Muscle enlargement alone does not mean oedematous swelling and active disease. Neither ultrasound, nor any combination of 11 clinical and laboratory parameters provided the degree of information on muscles and connective tissue that was obtainable by MRI. In unclear cases of recently developed diplopia, before orbital decompression surgery, in the case of treatment failure or if, for any other reason, imaging is needed in GO, MRI is the method of choice.

Adult↗
PubMed2000

Effects of aging on efficiency of task switching in a variant of the trail making test.

The Trail Making Test (TMT; R. M. Reitan, 1958, 1992) is extensively used in research in neuropsychology and in aging, in part because it has been postulated to reflect executive processes, such as planning and switching. However, neurocognitive and individual-difference-based analyses of this test are complicated because of different spatial arrangements of targets, the use of letters only in Version B, and potential order effects when Version A is administered prior to Version B. The present article examines a variant of a TMT (called the Connections Test) that attempts to remedy these deficiencies. A structural equation model suggested that there were no direct effects of age on either the nonalternating or alternating versions of the Connections Test (analogous to TMT Versions A and B, respectively); rather, all age-related effects were mediated through effects on perceptual speed. Moreover, although the nonalternating and alternating versions were strongly related to one another, only the latter had significant independent relations with measures of higher order cognition.

Adolescent↗
PubMed1999

Incidence and time of occurrence of regional recurrence in stage I-II breast cancer: value of adjuvant irradiation.

PURPOSE: The value of adjuvant radiation therapy (RT) of the axilla and supraclavicular fossa is controversial in early-stage breast cancer. This retrospective study was undertaken to identify pathological risk factors that would predict which subsets of patients would benefit from regional nodal irradiation (RNI). METHODS AND MATERIALS: A total of 1309 women with Stage I/II breast cancer underwent full axillary dissection and either mastectomy (n = 894) or breast-conserving surgery (n = 415). Of these, 712 patients received RNI. The median axilla/supraclavicular fossa dose was 50 Gy. RESULTS: The 10-year actuarial rate of axillary failure (AXF) was 0. 5% in N0 and 2.8% in N1 patients (p 5, also correlated with AXF; the respective rate was 4.3% vs. 1.2% (p = 0.0142). Neither the incidence of AXF nor the time to AXF was affected significantly by the use of RNI, but in N1 patients with retrieved nodes < or = 5, the rate of AXF was 8.3% without RNI vs. 0% with RNI (p = 0.2340). The 10-year actuarial rate of supraclavicular failure (SCF) was 1.2% in N0 and 6.3% in N1 patients (p = 0.0000). SCF was also associated with the extent of nodal involvement (p = 0.0031). The incidence of SCF was not significantly affected by the use of RNI. However, when the results of N1bii and N1biv patients were evaluated as a single group, the effect of RNI was significant (p = 0.0358). The rates of SCF without RNI were high in patients with N1bii or N1biv stage: 10% and 37.5% and, with RNI, 3.2% and 18.2%, respectively. These findings were reinforced by the various combinations of T- and N1-stage. The mean time to SCF was 53.6 months in the irradiated and 24.9 months in the nonirradiated patients (p = 0.0007). CONCLUSIONS: After a complete axillary dissection, only N1 patients with retrieved nodes < or = 5 may be considered for axillary RT. Elective supraclavicular RT is suggested for patients with N1bii or N1biv stage. Supraclavicular irradiation decreases the incidence and delays the appearance of SCF.

Adult↗
PubMed1999

Topical ephedrine administration and nasal chemosensory function in healthy human subjects.

OBJECTIVE: To investigate dose-related effects of ephedrine on olfactory function in healthy subjects. DESIGN: Placebo-controlled, randomized, double-blind study. METHODS: Drug effects were assessed using olfactory and trigeminal psychophysical measures (intensity ratings, odor discrimination, butanol and formic acid thresholds); nasal patency was assessed by means of anterior rhinoresistometry. The investigation was performed in 24 healthy volunteers; subjects were assigned to treatments A, B, or C (3 groups with 8 subjects each; 4 women and 4 men per group). All subjects received either placebo or ephedrine in both nostrils; group A subjects received placebo, and group B and C subjects received ephedrine in dosages of 0.12 and 0.24 mg, respectively. RESULTS: Treatment with ephedrine produced a tendency toward an increase of nasal airflow. However, during the time of observation there was no significant difference between effects produced by the 2 dosages. Ephedrine had no systematic effect on measures of olfactory function. The only significant correlation to the nasal airflow was found for perceived intensity of the trigeminal stimuli, which increased with increasing flow. CONCLUSIONS: Ephedrine appeared to have neither negative nor major positive effects on intranasal chemosensory function in healthy subjects. This indicates that ephedrine may be used as a decongestant in studies on olfaction.

Administration, Intranasal↗
PubMed1999

Cellular responses to whitlockite.

Whitlockite crystals have been observed in both degenerating and normal articular cartilages. To determine their potential for inducing cartilage degeneration, we studied their ability to induce mitogenesis and synthesis and secretion of metalloproteases in vitro. Whitlockite crystals were found to stimulate cell proliferation and to stimulate synthesis and secretion of stromelysin and collagenase. However, they were less stimulatory than crystals that contained calcium (Ca) and phosphate without magnesium substitution for Ca. Whitlockite crystals elicit biologic cellular responses that suggest potential pathogenicity in arthritis, but are less potent than Ca phosphate crystals without magnesium.

Calcium Phosphates↗