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Biomedical subjects

A Klein

Publications and source records attributed to A Klein.

At least 91 records · Page 5Linked to original sources

Electron paramagnetic resonance and spectroscopic characteristics of electrogenerated mixed-valent systems [(eta 5-C5Me5)M(mu-L)M(eta 5-C5Me5)]+ (M = Rh, Ir; L = 2,5-diiminopyrazines) in relation to the radicals [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]+ and [(eta 5-C5Me5)M(mu-L)MCl(eta 5-C5Me5)]2+.

Electrochemical reduction of the dinuclear [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]2+ ions (M = Rh, Ir; L = 2,5-bis(1-phenyliminoethyl)pyrazine (bpip) and 2,5-bis[1-(2,6-dimethylphenyl)iminoethyl]pyrazine (bxip)) proceeds via the paramagnetic intermediates [(eta 5-C5Me5)ClM(mu-L)MCl(eta 5-C5Me5)]+ (L = bpip) or [(eta 5-C5Me5)M(mu-L)MCl(eta 5-C5Me5)]2+ (L = bxip) and [(eta 5-C5Me5)M(mu-L)M(eta 5-C5Me5)]+. Whereas the first is clearly a radical species with a small g anisotropy, the chloride-free cations are distinguished by structured intervalence charge transfer (IVCT) bands in the near-infrared region and by rhombic electron paramagnetic resonance features between g = 1.9 and g = 2.3, which suggests considerable metal participation at the singly occupied MO. Alternatives for the d configuration assignment and for the role of the bisbidentate-conjugated bridging ligands will be discussed. The main difference between bpip and bxip systems is the destabilization of the chloride-containing forms through the bxip ligand for reasons of steric interference.

Journal Article↗

Stem cell factor plays a major role in the recruitment of eosinophils in allergic pleurisy in mice via the production of leukotriene B4.

The understanding of the mechanisms underlying eosinophil migration into tissue is an essential step in the development of novel therapies aimed at treating allergic diseases where eosinophil recruitment and activation are thought to play an essential role. In this study, we have examined the effects of the in vivo administration of stem cell factor (SCF) on eosinophil recruitment and tested whether endogenous SCF was involved in mediating eosinophil recruitment in response to Ag challenge in sensitized mice. The intrapleural injection of SCF induced a time- and concentration-dependent recruitment of eosinophils in mice. In allergic mice, SCF message was expressed early after Ag challenge and returned to baseline levels after 8 h. In agreement with the ability of SCF to induce eosinophil recruitment and its expression in the allergic reaction, an anti-SCF polyclonal Ab abrogated eosinophil recruitment when given before Ag challenge. SCF increased the levels of leukotriene B4 (LTB4) in the pleural cavity of mice and an LTB4 receptor antagonist, CP105,696, abrogated the effects of SCF on eosinophil recruitment. Similarly, recruitment of eosinophils in the allergic reaction was virtually abolished by CP105,696. Together, our data favor the hypothesis that the local release of SCF following Ag challenge may activate and/or prime mast cells for IgE-mediated release of inflammatory mediators, especially LTB4. The mediators released in turn drive the recruitment of eosinophils. Inhibition of the function of SCF in vivo may reduce the migration of eosinophils to sites of allergic inflammation and may, thus, be a relevant principle in the treatment of allergic diseases.

Animals↗

Detection of micrometastasis by cytokeratin-20 (reverse transcription polymerase chain reaction) in lymph nodes of patients with endometrial cancer.

BACKGROUND: Cytokeratins are constituents of the intermediate filaments (IFs) of epithelial cells which are expressed in various combinations, depending on the type of epithelium and degree of differentiation. We have reported (R. Zemer, A. Fishman, J. Bernheim, S. Zimlichman, O. Markowitz, M. Altaras, and A. Klein, Gynecol Oncol 70:410-413, 1998) on the determination of cytokeratin-20 (CK-20) by reverse transcription polymerase chain reaction (RT-PCR) in the detection of endometrial cancer cells as a potential biomarker. In that study, we also found that by using immunocytochemistry, most carcinomas were found to be negative for CK-20. The sensitivity and specificity rates obtained by using the RT-PCR method were 94.4 and 91%, respectively. OBJECTIVE: The aim of this study is to investigate the feasibility and potential of the specific mRNA marker, CK-20, to detect endometrial cancer cells-micrometastases (MMs)-by RT-PCR in lymph node (LN) samplings of patients undergoing hysterectomy for endometrial carcinoma. METHOD: We used the RT-PCR method to determine the expression of CK-20 in the LNs of 20 patients [study group (SG)] who were being surgically staged and treated for endometrial carcinoma. The specificity of the mRNA CK-20 marker was examined in LNs obtained from five healthy patients [control group (CG)] who underwent abdominal hysterectomy and bilateral salpingo-oopherectomy for benign gynecologic conditions. The LNs obtained from the SG and CG patients were prepared together before mRNA extraction. RNA of the various cell pellets was extracted and RT-PCR was performed with CK-20 primers. RT-PCR products were analyzed by agarose gel electrophoresis and ethidium bromide staining against PCR size markers. Specificity of the RT-PCR products was examined by Southern blotting. RESULTS: Histopathologic examinations demonstrated the presence of metastases in two (10%) SG patients. These patients were also CK-20 positive. Of the remaining 18 patients with negative histopathologic results, 6 (33%) were CK-20 positive and 12 (67%) were negative. All the CG patients were CK-20 negative (specificity, 100%). CONCLUSIONS: The results obtained in this study suggest that RT-PCR of CK-20 is more sensitive than traditional histopathologic methods in the diagnosis of MMs in LNs of patients with endometrial cancer. Thus, due to the aforementioned characteristics of CK-20, it may be considered a powerful biomarker in the detection of MMs in LNs of patients with endometrial cancer.

Adenocarcinoma↗

Detection of tumor circulating cells by cytokeratin 20 in the blood of patients with endometrial carcinoma.

BACKGROUND: Cytokeratins are constituents of the intermediate filaments of epithelial cells which are expressed in various combinations depending on the epithelial type and the degree of differentiation. Using the reverse transcriptase-polymerase chain reaction technique (RT-PCR) we recently demonstrated that: (1) Cytokertin 20-the most recent discovered cytokeratin-is expressed in endometrial carcinoma tumors but not in the endometrium of patients with benign diseases, and (2) CK-20 is not expressed in blood cells. The aim of this study is to examine whether CK-20 expression in blood can be used as a biomarker for the detection of the dissemination of malignant cells in patients treated for endometrial carcinoma. METHODS: In the present study, we have used RT-PCR to determine the expression of CK-20 in the peripheral blood of the following groups: (1) preop new diagnosed patients (n = 20), (2) patients with no clinical evidence of disease following completion of definitive treatment (n = 33; 17 at low risk; 16 at high risk), (3) patients with recurrent disease (n = 6), and (4) a control group of healthy subjects (n = 16). RNA was extracted from cell pellets and analysed by RT-PCR using primers for CK-20. RESULTS: Of the 20 patients of the first group 7 (35%) were CK-20 positive. Of the 33 patients of the second group 17 (51%) were CK-20 positive. Subdivision of this group showed that 9 of 17 (53%) were positive in the low-risk subgroup, and 8 of 16 (50%) were positive in the high-risk subgroup. All 6 patients with recurrent disease were positive, and all subjects in the control group were negative. CONCLUSION: These results indicate that RT-PCR of CK-20, because of its high sensitivity, is a potential biomarker for detecting metastasis in blood samples of patients with endometrial carcinoma.

Biomarkers, Tumor↗

Influence of the fusion of two subunits of the F420-non-reducing hydrogenase of Methanococcus voltae on its biochemical properties.

In Methanococcus voltae, one of the two [NiFeSe] hydrogenases is unusual in that the large subunit is split into two subunits, each contributing two ligands to the [NiFe] center that catalyzes the heterolytic cleavage of the dihydrogen molecule. We have engineered a fusion of these two subunits. The resulting new enzyme showed no significant difference in hydrogen uptake activity or in the Ni-C or Ni-L EPR spectra compared to the the wild-type enzyme, but exhibited a tenfold increase in both the Km for hydrogen and the Ki for the competitive inhibitor carbon monoxide.

Binding Sites↗

[Candida endophthalmitis in drug abuse. case report.

BACKGROUND: Endogenous fungal endophthalmitis is mostly seen as opportunistic infection, particularly in immunocompromised patients and under special risk factors. The therapeutical approach and the value of vitrectomy in diagnosis and therapy are discussed. PATIENT: A 42-years-old intravenous heroin addicted male patient with unilateral Candida albicans endophthalmitis, determined by cultivation is presented. The visual acuity at initial was 20/25 but decreased to hand-movements within 14 days despite systemic therapy. Treatment with systemic Fluconazole was extended and vitrectomy performed. The infection resolved but left a scar in the macula. The patient recovered a visual acuity of 20/80. CONCLUSION: Candida albicans endophthalmitis is a dreaded situation in ophthalmology. It has poor visual prognosis if left untreated. Therefore immediate diagnosis and aggressive therapy, if necessary vitrectomy are required.

Adult↗

Teaching model for intraoperative spinal sonography in spinal fractures. An experimental study.

To improve the technique of intraoperative sonography of the spinal canal, a teaching model of the thoracolumbar spine was developed. It allows to simulate the typical spinal stenosis of a vertebral fracture and the sonographic procedure to detect and measure such a lesion. Moreover, partial laminectomy and modification of a fixateur interne set-up, which are preconditions for successful sonography, can be simulated. Independent of the surgical qualification, a high precision in sonographic localisation and measurement of the spinal canal stenosis was achieved by the training. The results could be validated in the cadaveric model. Thus, sonographic expertise acquired with the teaching model proved to be reliable in the clinical situation.

Cadaver↗

Cumulative experience with pediatric living related liver transplantation.

PURPOSE: This study reports the authors' cumulative experience with pediatric living related orthotopic liver transplantation. METHODS: The charts of all patients who received living-related liver transplantation to study complications of transplant surgery, immunosuppression, rejection, and overall survival rate were reviewed retrospectively. RESULTS: Between November 1992 and October 1998, 30 children underwent living-related liver transplantation. Patients were between the ages of 3 months and 7 years of age (mean, 28 months). All received left lateral segmental living-related transplants. At the time of transplant, 14 of 30 patients were listed as United Network of Organ Sharing (UNOS) status 3, 11 were listed as UNOS status 2B, and 5 were listed as UNOS status 1. Indications for transplant included biliary atresia (n = 21), alpha-1-antitrypsin deficiency (n = 2), hepatitis C (n = 2), giant cell hepatitis (n = 2), hepatoblastoma (n = 1), valproic acid toxicity (n = 1), and hemangioendothelioma (n = 1). All donors were parents except for one uncle. There were no major donor complications. Minor complications included wound infection (n = 4), ventral hernia (n = 2), postoperative gastric dysmotility (n = 2), and 1 case of central line-related pneumothorax (n = 1). All but 4 recipients received primary tacrolimus immunosuppressive regimens, and the other 4 underwent conversion from cyclosporine. Initial tacrolimus therapy was begun at 0.15 mg/kg/dose PO/NG every 12 hours. Concomitant immunosuppression included methylprednisolone and mycophenolate mofetil. Fifty-three percent of patients experienced at least 1 episode of rejection, and 27% experienced multiple episodes. Immediate postoperative complications included primary nonfunction (n = 2), vascular thrombosis (n = 3), biliary leaks (n = 3), and infections (n = 17). Two patients (n = 2) required retransplantation. Complications of immunosuppressive therapy included persistent systemic hypertension (n = 6), renal tubular acidosis (n = 3), short-term hyperglycemia (n = 2), neurotoxicity (n = 2), nephrotoxicity (n = 2), food allergies (n = 8), and posttransplant lymphoproliferative disease (n = 4). All patients with PTLD were treated with immunosuppression reduction or withdrawal. Two of 4 had disease progression requiring chemotherapy. The majority of complications were treated with dose adjustments. There were 4 early deaths (13%): 1 of primary nonfunction, 2 of sepsis, and 1 of arrhythmia and renal failure. There was 1 late death of recurrent disease. Twenty-five patients (83%) are alive at 3 months to 6 years post-transplant. CONCLUSION: Living-related orthotopic liver transplantation is an effective intervention for pediatric patients with end-stage disease.

Child↗

Regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing: a comparison with stress echocardiography and perfusion scintigraphy.

OBJECTIVES: We evaluated regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing. BACKGROUND: Evaluation and quantification of diastolic myocardial function remain a challenge for imaging techniques in stress tests. METHODS: A prospective study compared the detection of coronary artery stenosis: 1) by pulsed Doppler myocardial mapping, 2) by two-dimensional echocardiographic dobutamine stress test, and 3) by perfusion scintigraphy in 64 patients using coronary angiography for reference. An age matched subgroup of 10 patients with normal angiograms and two-dimensional echocardiographic stress test served as control group. Peak myocardial contraction velocity (Vc) and lengthening rate during early diastolic left ventricular (LV) filling (VE) were measured in 12 LV segments from three apical views. RESULTS: In controls, myocardial velocities increased during stress by > or =3.6 cm/s (p < 0.001). In LV segments depending on a stenosed artery (n = 70), VE decreased by > or =1 cm/s and, thus, was different from control segments (n = 112, p < 0.001) and from scar segments (n = 13, p < 0.01), whereas the change of Vc was similar to that in scar segments. A stress induced 2 cm/s reduction of VE discerned the best diagnostic accuracy (sensitivity 84%, specificity 93%) in comparison with two-dimensional echocardiography (78% and 71%) and perfusion scintigraphy (61% and 86%). Using receiver operating curves at incremental levels of luminal narrowing, these relations persisted. CONCLUSIONS: Quantification of diastolic myocardial function by pulsed Doppler myocardial mapping during dobutamine stress test was shown to be a feasible, accurate, reproducible, noninvasive technique that should be considered to be a sensitive alternative to the present echocardiographic and scintigraphic imaging techniques for stress tests.

Cardiotonic Agents↗

Exploration of mixed-valence chemistry: inventing new analogues of the Creutz-Taube ion.

Starting from the Creutz-Taube ion as the prototype of a molecule-bridged mixed-valent complex, a number of related systems are presented in which the metal, the co-ligands, the molecular bridge, the d electron configuration, the medium, the charge, the coordination mode, or the nuclearity have been modified. The new mixed-valent configurations, as obtained through various chemical approaches, display different stabilities and spectroscopic characteristics in relation to the Creutz-Taube ion; the analysis of these results serves to provide a better understanding of fundamental aspects of molecule-mediated metal-metal interaction.

Cations↗

Chemosensitivity of B cell chronic lymphocytic leukemia and correlated expression of proteins regulating apoptosis, cell cycle and DNA repair.

B cell chronic lymphocytic leukemia (B-CLL) cannot be cured with conventional chemotherapy. This clinical enigma appears to be at least partially due to the fact that B-CLL cells are resistant to programmed cell death (apoptosis) and that they are arrested in G0/G1 phase of the cell cycle. The reasons for the dysregulation of these two key cellular events in B-CLL are unclear. The present study aimed at determining correlations between the expression levels of proteins regulating apoptosis, cell cycle and DNA repair in B-CLL cells and normal B cells. In addition, the differential sensitivity of B-CLL cells to drug-induced apoptosis was quantified. We show that in B-CLL cells levels of the death-suppressor Bcl-2 correlated positively with those of the pro-apoptotic protein Bax and of the cyclin-dependent kinase (cdk) inhibitor p27Kip1. In B-CLL cells levels of the anti-apoptotic Bcl-xL showed a positive correlation with levels of the 80 kDa regulatory component (Ku80) of the DNA-dependent protein kinase that is involved in DNA double-stranded break repair. These correlations were not detected in normal B cells. The sensitivity of leukemic cells to FLUD but not to ADM, CPM or to DEX was reduced in pre-treated patients. These data support the hypothesis that in B-CLL cells death-modulators and molecules modulating cell cycle and DNA repair are regulated in a coordinated manner. Leukemia (2000) 14, 40-46.

Antineoplastic Agents↗

Conversion of the central [4Fe-4S] cluster into a [3Fe-4S] cluster leads to reduced hydrogen-uptake activity of the F420-reducing hydrogenase of Methanococcus voltae.

As in many other hydrogenases, the small subunit of the F420-reducing hydrogenase of Methanococcus voltae contains three iron-sulfur clusters. The arrangement of the three [4Fe-4S] clusters corresponds to the arrangement of [Fe-S] clusters in the [NiFeSe] hydrogenase of Desulfomicrobium baculatum. Many other hydrogenases contain two [4Fe-4S] clusters and one [3Fe-4S] cluster with a relatively high redox potential, which is located in the central position between a proximal and a distal [4Fe-4S] cluster. We have investigated the role of the central [4Fe-4S] cluster in M. voltae with regard to its effect on the enzyme activity and its spectroscopic properties. Using site-directed mutagenesis, we constructed a strain in which one cysteine ligand of the central [4Fe-4S] cluster was replaced by proline. The mutant protein was purified, and the [4Fe-4S] to [3Fe-4S] cluster conversion was confirmed by EPR spectroscopy. The conversion resulted in an increase in the redox potential of the [3Fe-4S] cluster by about 400 mV. The [NiFe] active site was not affected significantly by the mutation as assessed by the unchanged Ni EPR spectrum. The specific activity of the mutated enzyme did not show any significant differences with the artificial electron acceptor benzyl viologen, but its specific activity with the natural electron acceptor F420 decreased tenfold.

Amino Acid Sequence↗

Dark skin tissue reaction in laser assisted hair removal with a long-pulse ruby laser.

BACKGROUND: Photo-epilation has become an accepted modality for the removal of unwanted hair. However, adverse effects may occur in darker skin patients. Treatment with the ruby laser is generally advised for skin types I-III. Treatment of over 3000 patients (skin types I-III) in our clinic has resulted in a minimal percentage (approximately 3%) of adverse effects. Increasing pulse duration should allow the epidermis to cool and thus minimize thermal damage so that treatment can be extended to dark skin patients. OBJECTIVES: The purpose of our study was to compare tissue reaction in dark skin patients (skin type IV) after treatment with a long-pulse (20 msec) ruby laser and compare the reaction with a 1 msec ruby laser treatment. RESULTS: Hair removal efficacy was determined to be similar with both pulse durations, but tissue reaction was more severe, including eschar and hypopigmentation, following treatment of dark skin patients with the 1 msec protocol. Increasing the pulse duration to 20 msec appears to result in safe and efficacious ruby laser treatment even for darker skinned patients.

Hair Removal↗

[Ultrasound anatomy of the sciatic nerve of the thigh].

Ultrasound examinations of the sciatic nerve were performed using high-resolution transducers (7.5, 10 to 20 MHz) both in anatomical specimens and in healthy volunteers. The ultrasonographic anatomy (sono-anatomy) of the nerve, its course along the thigh and its echogenicity in comparison with muscles, tendons and adipose tissue were investigated in 10 isolated muscle/nerve preparations. In addition, the influence of the angle of the applied transducer on the various different tissues was evaluated. In the clinical part of the study, the sciatic nerve was identified ultrasonographically in both thighs of 50 sex-matched healthy volunteers aged between 2 and 76 years. The normal sciatic nerve presents as a tubular echogenic structure with parallel linear internal echoes in the longitudinal section, and as a punctiform moderately echoic structure in cross-section, with the perineurium producing bright boundary echoes. Varying the insonating angle of the transducer reduced echogenicity, but to a smaller degree than in muscles and tendons. Unequivocal identified of the sciatic nerve from the level of the gluteal fold to its bifurcation in the distal thigh was possible in all but one case. We conclude that the course of the sciatic nerve along the thigh can be reliably identified and imaged with high-resolution ultrasound.

Adolescent↗

Self-reflection and well-being: is there a healthy amount of introspection?

Both extremely high and extremely low self-reflection have been considered as risk factors for psychological maladjustment. Therefore, from an integrating perspective medium amounts of self-reflection may constitute "healthy introspection." To test this hypothesis, self-reflection and psychological well-being were measured with self-report tests given a pooled sample of 647 subjects. A regressive relationship with self-reflection as a quadratic predictor of well-being was estimated using the LMS method for nonlinear structural equation modeling. No evidence for a curvilinear effect was detected in the total sample or in subgroups. Alternative theoretical assumptions are discussed on a psychological and operational level.

Adolescent↗