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Biomedical subjects

I Fuchs

Publications and source records attributed to I Fuchs.

At least 37 records · Page 2Linked to original sources

[The clinical importance of keratin 18 in breast cancer].

OBJECTIVE: This study was performed to determine the prognostic significance and the biological function of the structure protein keratin 18 (K18) in a group of patients with breast cancer. MATERIAL AND METHODS: Paraffin sections from the primary tumors in 80 patients with breast cancer were examined for the expression of K18 by immunohistochemical staining with the monoclonal antibody CK2. The intensity of the expression measured by an immune reactive score (IRS) was compared with clinicopathological variables and follow-up data up to 10 years. Additionally K18 expression in different human breast cancer cell lines with well defined metastatic behavior were investigated to confirm the clinical data. RESULTS: A marked positive staining was observed in 13 (16.2%) women. Mortality rate in this group was 7.7% and 46.3% in the group with a low K18 expression. The recurrence rate was with 15.4% significantly lower in the positive group than in the negative group with 56.7%. Irrespective of the morphological tumor stage, almost all patients with strong K18 expression were still free of disease after 10 years. This clinical finding is supported by observations in cell cultures. CONCLUSIONS: In our collective K18 expression was found to be an independent and significant predictor for disease-free and overall survival.

Adult↗

Measurement of nitrite and nitrate in plasma, serum and urine of humans by high-performance liquid chromatography, the Griess assay, chemiluminescence and gas chromatography-mass spectrometry: interferences by biogenic amines and N(G)-nitro-L-arginine analogs.

In this paper, the HPLC method for the measurement of nitrite and nitrate in serum of humans newly reported by E1 Menyawi et al. is discussed, especially in regard to the extremely low nitrate levels measured in serum of healthy humans. From the discussion, it is concluded that: (1) Biogenic amines at physiological concentrations do not significantly interfere with the batch Griess assay. (2) The HPLC method of E1 Menyawi et al. does not reveal accurate levels for serum nitrate. (3) In serum and plasma of healthy humans, nitrate ranges within 15-70 microM. (4) Exogenous NG-nitro-L-arginine analogs can interfere with the measurement of nitrate in human plasma and urine by the batch Griess assay, chemiluminescence and GC-MS; interferences can be effectively eliminated by solid-phase extraction on cation-exchangers.

Artifacts↗

[Folic acid deficiency in chronically hospitalized mental patients].

Studies over the past 30 years have shown a relationship between folic acid deficiency and psychopathology. FA deficiency was observed more often in depressed and in psychotic patients, in alcoholics, in those suffering from organic mental disorders and in the psycho-geriatric population. In a chronic inpatient population of 120 patients, of the 106 in whom FA serum levels were examined, only 1 had a definitely subnormal level. An additional 16 had close to the lower limit of normal (2 ng/ml) and were considered borderline cases. FA-deficient and borderline patients were then compared to matched patients with normal FA levels on the MMSE and PANSS scales by blinded raters. Small differences were found between the 2 groups. The FA-deficient and borderline patients had more organic and psychotic symptoms, but the differences were not statistically significant.

Folic Acid↗

Quantitative electromyography-guided botulinum toxin treatment of cervical dystonia.

The purpose of this study was to investigate the clinical and electromyographic effect of turn/amplitude analysis (TAA)-guided botulinum toxin administration in patients with cervical dystonia. Involuntary electromyographic activity was recorded from both sternocleidomastoidei, both splenii capites, and both trapezii muscles of 13 torticollis patients, aged 34-73 years, before and after botulinum toxin A (Dysport) application. Dystonic muscles were selected for the injection if mean turns/s exceeded a level of 200. Four weeks after treatment with a mean dose of 223 mu/subject, clinical improvement was observed in 12 patients (92%) and only one patient reported no effect. Electromyographic improvement could be observed in 10 patients (77%). Both turns/s and the amplitude/turn decreased by 27% on the average after treatment. The electromyographic toxin effect showed a good correlation with the clinical toxin effect (r = 0.6). No dose dependency of the changes in turn/amplitude parameters could be observed. We found TAA a valuable modality for targeting and selecting dystonic muscles and for assessing the therapeutic benefit of the toxin.

Adult↗

Automatic EMG-guided botulinum toxin treatment of spasticity.

Conventional electromyographic (EMG) guidance in botulinum toxin therapy can localize a muscle, but the amount of electrical activity is assessed only subjectively. We wanted to introduce a quantitative EMG criterion, according to which the decision for/against toxin application could be made. Turn/amplitude analysis (TAA) was applied to nine patients with severe paraspasticity (n = 5), right upper or lower limb spasticity (n = 3), or tetraspasticity (n = 1) before and after toxin administration. Muscles were selected for toxin application if both mean turns/second and mean amplitude/turn exceeded the level of 150. A mean Dysport dose of 116 mouse units (mu) (range 40-240 mu) was administered to each of the 26 muscles that met the EMG criterion. Thirty days after the injection, activities of daily living, pain, and TAA count improved in 89%, tone in 78%, and range of motion in 56% of the patients by at least 1 point on corresponding 5-point rating scales. TAA provides a useful EMG criterion for/against botulinum toxin application. Muscle selection according to this criterion leads to a significant subjective and objective toxin effect. TAA is a valuable tool to determine the benefit of single and subsequent botulinum toxin injections in the treatment of spasticity.

Adult↗

Elevated keratin 18 protein expression indicates a favorable prognosis in patients with breast cancer.

This study was performed to determine if keratin 18 (K18) has prognostic significance in breast cancer cell lines and patients with breast carcinoma. Paraffin sections of primary breast carcinoma tumors and human breast carcinoma cell lines were examined for K18 expression by immunohistochemical staining with the monoclonal antibody CK2. K18 protein expression was low in highly metastatic cell lines and, conversely, high in weakly metastatic cell lines, suggesting that it may function as a prognostic indicator. K18 expression was consequently examined in 134 patients with breast cancer. The staining intensity was compared with clinicopathological variables and follow-up data spanning 8 years. A definitive positive staining was observed in 22 (16.4%) women. The mortality rate was 4. 5% in the K18-positive group and 44.6% in the K18-negative group. Multivariate analysis found K18 expression to be an independent and significant predictor for overall survival.

Adult↗

Central and peripheral minocycline suppresses motor activity in rats.

Minocycline (MIN) HCl is a tetracycline derivative previously shown to inhibit agonist-induced accumulation of cyclic adenosine monophosphate (cAMP) in vitro and suppress motor activity and amphetamine-induced hyperactivity in rats following SC injection. The present study examined the effect of IV and intracerebral MIN on baseline activity and amphetamine-induced hyperactivity. IV MIN suppressed both types of activity in doses of 100 and 150 mg/kg. When injected ICV, MIN (50 micrograms/2 microliter) suppressed the increase in rearing elicited by amphetamine but did not affect baseline activity. MIN did not attenuate the behavioral suppression induced by the cAMP phosphodiesterase inhibitor rolipram. MIN apparently has centrally mediated effects on motor activity in rats; however, it is not yet possible to associate MIN's behavioral effects with its ability to inhibit agonist-induced stimulation of cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗

Life stressors and coping style are associated with immune measures in HIV-1 infection--a preliminary report.

OBJECTIVE: Life stressors and coping style have been associated with alterations in cellular immunity similar to those seen in HIV-1 infection. The interval between infection with HIV-1 and the development of AIDS is lengthy and highly variable. This pilot study investigated whether life stressors and coping style may account for a portion of this variation. METHOD: A sample of eleven asymptomatic HIV-1 seropositive homosexual male volunteers responding to a local advertisement was assessed on life stressors, coping style and cellular phenotypic and functional immune measures--T4 "helper" cell/T8 "suppressor" cell ratio, T4 cell count, total lymphocyte count, and natural killer cell cytotoxicity. RESULTS: Significant associations were observed for both major life stressor impact over the previous year and passive coping style use with the total lymphocyte count; higher life stressor impact and passive coping style use were associated with lower total lymphocyte counts. Similarly, a trend in the same direction was found for the relationship of these two measures with the count of T4 cells, which are directly infected and killed by HIV-1. CONCLUSIONS: It is well documented that decrements in T4 cell and total lymphocyte counts are powerful predictors of subsequent clinical progression to AIDS. These preliminary findings suggest that life stressors and coping style may also be predictors of the development of AIDS.

Acquired Immunodeficiency Syndrome↗

Myo-inositol attenuates two specific behavioral effects of acute lithium in rats.

Acute and chronic lithium treatment reduces levels of brain myo-inositol in rats. Several biological effects of lithium can be reversed in vitro by addition of myo-inositol. The ability of myo-inositol to reverse behavioral effects of lithium was tested using chronic inositol administration or acute intracerebroventricular (i.c.v.) injections. Chronic myoinositol elevated activity during the first 10 min in an open field, but did not reverse lithium-induced hypokinesia. Myo-inositol (i.c.v.) reversed the suppression of rearing behavior 24 hrs after an acute dose of lithium (5 mEq/kg) but did not attenuate hypokinesia 24 hrs after a high dose of lithium (10 mEq/kg). Myo-inositol, but not the inactive isomer chiro-inositol (i.c.v.), also significantly prolonged the latency to clonus in the lithium pilocarpine seizure model. These studies suggest that reduction of brain myo-inositol may be a critical mechanism for the behavioral effects of lithium.

Animals↗

Met-enkephalin levels in midbrain dopamine regions of inbred mouse strains which differ in the number of dopamine neurons.

The Met-enkephalin content in tissue micropunches of the substantia nigra zona compacta, ventral tegmental area and the caudate nucleus in BALB/c and CBA mouse strains was measured by radioimmunoassay. The CBA strain had significantly higher Met-enkephalin levels in all 3 regions than the BALB/c strain. These differences should be taken into account when relating the intensity of dopamine-induced behaviors to the number of dopamine neurons.

Animals↗

Reassociation of dimeric cytoplasmic malate dehydrogenase is determined by slow and very slow folding reactions.

Malate dehydrogenase occurs in virtually all eucaryotic cells in mitochondrial and cytoplasmic forms, both of which are composed of two identical subunits. The reactivation of the mitochondrial isoenzyme has been the subject of previous studies [Jaenicke, R., Rudolph, R., & Heider, I. (1979) Biochemistry 18, 1217-1223]. In the present study, the reconstitution of cytoplasmic malate dehydrogenase from porcine heart after denaturation by guanidine hydrochloride has been determined. The enzyme is denatured by greater than 1.2 M guanidine hydrochloride; upon reconstitution, approximately 60% of the initial native enzyme can be recovered. The kinetics of reconstitution after maximum unfolding by 6 M guanidine hydrochloride were analyzed by fluorescence, far-ultraviolet circular dichroism, chemical cross-linking with glutaraldehyde, and activity measurements. After fast folding into structured intermediates (less than 1 min), formation of native enzyme is governed by two parallel slow and very slow first-order folding reactions (k1 = 1.3 X 10(-3) S-1 and k2 = 7 X 10(-5) S-1 at 20 degrees C). The rate constant of the association step following the slow folding reaction (determined by k1) must be greater than 10(6) M-1 S-1. The energy of activation of the slow folding step is of the order of 9 +/- 1 kcal/mol; the apparent rate constant of the parallel very slow folding reaction is virtually temperature independent. The intermediates of reassociation must be enzymatically inactive, since reactivation strictly parallels the formation of native dimers. Upon acid dissociation (pH 2.3), approximately 35% of the native helicity is preserved, as determined by circular dichroism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Eating behavior and plasma beta-endorphin in bulimia.

To study the possible role of plasma beta-endorphin in bulimia, we measured plasma beta-endorphin immunoreactivity in 34 female patients with normal-weight bulimia and 34 normal female controls matched for weight as percent of ideal. Plasma beta-endorphin immunoreactivity in bulimics (mean 59.6 pg/ml; SEM 5.6) was significantly lower (p less than 0.05) than in controls (mean 79.5 pg/ml; SEM 8.5). Within the bulimic group, plasma beta-endorphin immunoreactivity correlated inversely with severity of bulimic symptomatology as measured by the Eating Attitudes Test Bulimia Subscale (p less than 0.05). Endorphin level did not correlate with severity of depression or with percent ideal body weight. Abnormalities in opioid metabolism may be implicated in eating disorders and account for the addictive properties of these disorders.

Adult↗

Influence of glutathione on the reactivation of enzymes containing cysteine or cystine.

Refolding of dimeric porcine cytosolic or mitochondrial malate dehydrogenases and of tetrameric pig heart and skeletal muscle lactate dehydrogenases (containing 5-7 cysteine residues), as well as reformation of the four cystine cross-bridges of bovine pancreatic ribonuclease, were studied in the presence of reduced and oxidized glutathione (GSH and GSSG). At the intracellular GSH level (5 mM) reduced ribonuclease can be reoxidized by 0.01-0.5 mM GSSG (pH 7.4) both at 20 degrees C and 37 degrees C. In this physiological range of GSSG concentrations and pH, the dehydrogenases show at least partial reactivation. With GSSG concentrations greater than 5 mM, reactivation is found to be completely inhibited for all the enzymes given. The results show that at the intracellular level of GSH and GSSG, thiol groups in reduced, unfolded ribonuclease are oxidized to form intramolecular cystine cross-bridges, while thiol groups of typical cysteine enzymes, such as lactate and malate dehydrogenase, remain in their reduced state during refolding. The rate of reactivation of lactate dehydrogenase (porcine muscle) is not affected by GSSG. In the case of ribonuclease, increasing concentrations of GSSG increase the rate of reactivation: At 20 degrees C, the halftime of the correct disulfide bond formation varies from approximately equal to 80 h in the presence of 0.01 mM GSSG to approximately equal to 10 h in the presence of 0.25 mM GSSG. A further increase in the rate of reactivation at higher GSSG concentrations is accompanied by a decrease in yield. Reactivation of ribonuclease is also observed at the low glutathione level found in blood plasma (5-25 microM GSH).

Animals↗

Blood pressure elevation in rats by peripheral administration of Tyr-Gly-Gly-Phe-Met-Arg-Phe and the invertebrate neuropeptide, Phe-Met-Arg-Phe-NH2.

Phe-Met-Arg-Phe-NH2 (FMRFamide), injected at less than 1 mumol/kg intravenously in the anesthetized rat, produces sharp elevations of blood pressure and changes in respiration. The effects were dependent on the carboxyterminal Arg-Phe (RF) configuration and were stereospecific for these two amino acids. A related peptide with RF carboxyterminus, gamma 1-melanotropic stimulating hormone, also had potent blood pressure stimulating activity. The mechanisms underlying the pressor effect of FMRFamide have not yet been established but this pressor action was not significantly attenuated by standard pharmacologic antagonists or prevented by removal of the adrenal or pituitary gland.

Animals↗

Normal limits of urinary excretion of eleven enzymes.

Urinary excretion of lactate dehydrogenase, hydroxybutyrate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, arylsulphatase A, alpha-glucosidase, beta-galactosidase, trehalase, N-acetyl-beta-glucosaminidase, beta-glucuronidase, and leucinearylamidase was studies in a carefully selected group of 100 healthy subjects, 50 women and 50 men. Enzyme activities were assayed in 3-h morning samples after gel filtration of the urine. Activities were related to time volume, and to urinary creatinine concentration. Several transforming functions had to be applied to enzyme output data to obtain an approximation to gaussian frequency distribution. Men showed a significantly higher excretion of gamma-glutamyltransferase, alpha-glucosidase, trehalase, N-acetyl-beta-glucosaminidase,beta-glucuronidase, and leucine arylamidase activity than did women if enzyme activity was related to urinary time volume. Women excreted more lactate dehydrogenase, hydroxybutyrate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, alpha-glucosidase, trehalase, and N-acetyl-beta-glucosaminidase activity than did men, if urinary creatinine was used as the basis of reference. Reference intervals were calculated as 2.5 and 97.5 percentiles for both sexes.

Acetylglucosaminidase↗