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M Schneider

Publications and source records attributed to M Schneider.

At least 127 records · Page 7Linked to original sources
PubMed2001

Preparation of site-differentiated mixed ligand and mixed ligand/mixed metal metallacrowns.

Assembly reactions that can prepare reliably regioselective metallamacrocyclic complexes have been a target in the development of metallacrowns. To this end, a series of mixed ligand and mixed ligand/mixed metal metallacrowns have been synthesized in high yield and structurally characterized. Two distinct connectivities have been observed in these types of metallacrowns. The monomeric, vacant metallacrown with mixed ligand composition [12-MC(Ni(II)N(Hshi)2(pko)2-4)] (1a) shows the connectivity pattern [-O-Ni-O-N-Ni-N-]2 while the other Ni metallacrowns, [12-MC(Ni(II)N(shi)2(pko)2-4)] (2a) and the coupled [12-MC(Ni(II)N(shi))2(pko)2-4)][12-MC(Ni(II)N(shi))3(pko)-4)] (3a) fused metallacrowns as well as the mixed metal Mn-Ni metallacrown [12-MC(Ni(II)Mn(III)N(shi)2(pko)2-4)] (4a), follow the pattern [-Ni-O-N-]4. Also, three distinct arrangements of the chelate rings around the metal ions have been observed. The syntheses are completely general, allowing for the substitution of different ligands into the metallacrown core. Compounds 1 and 4 show the 6-5-6-5-6-5-6-5 arrangement, compounds 2 and 3(1) the 6-6-5-5-6-6-5-5, and the 3(2) component the 6-6-5-5-6-5-6-5. The obtained structures can be rationalized by balancing the charge at each metal site in the metallacrown. Variable temperature magnetic susceptibility measurements show that exchange interactions for all the compounds are weak and dominantly antiferromagnetic (e.g., 2a gives an exchange coupling of J = -1.2 cm(-1) with g = 2.2). In solution, the metallacrowns are shown to be stable both to decomposition and ligand exchange.

Journal Article↗
PubMed2001

Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disease of early childhood characterized by nonmalignant accumulation and multivisceral infiltration of activated T lymphocytes and histiocytes (macrophages). Cytotoxic T and natural killer (NK) cell activity is markedly reduced or absent in these patients, and mutations in a lytic granule constituent, perforin, were recently identified in a number of FHL individuals. Here, we report a comprehensive survey of 34 additional patients with FHL for mutations in the coding region of the perforin gene and the relative frequency of perforin mutations in FHL. Perforin mutations were identified in 7 of the 34 families investigated. Six children were homozygous for the mutations, and one patient was a compound heterozygote. Four novel mutations were detected: one nonsense, two missense, and one deletion of one amino acid. In four families, a previously reported mutation at codon 374, causing a premature stop codon, was identified, and, therefore, this is the most common perforin mutation identified so far in FHL patients. We found perforin mutations in 20% of all FHL patients investigated (7/34), with a somewhat higher prevalence, approximately 30% (6/20), in children whose parents originated from Turkey. No other correlation between the type of mutation and the phenotype of the patients was evident from the present study. Our combined results from mutational analysis of 34 families and linkage analysis of a subset of consanguineous families indicate that perforin mutations account for 20%-40% of the FHL cases and the FHL 1 locus on chromosome 9 for approximately 10%, whereas the major part of the FHL cases are caused by mutations in not-yet-identified genes.

Amino Acid Substitution↗
PubMed2001

Morphometric assessment of testicular changes in drug-related fatalities.

Testicular sections of 50 deceased drug addicts were examined by light microscopy using morphometric methods and determining the extent of spermatogenesis by application of the Johnsen score count. Twenty cases of violent death served as reference sample. The study was aimed at obtaining data about the degree of germinal gland damage following the duration of the individual drug career, which was correlated to the histologic findings. Progressively reduced maturation of germinal cells, decrease of tubular diameter and height of sperm-producing epithelium were found the longer the individual case history has been. The results clearly indicated a substantial impairment of male fertility in the course of a drug career, but etiology seems to be multifactorial, since most of the deceased were polytoxicomanic and more than 40% were under the influence of alcohol at the time of death. Testicular damage is obviously a sequel of long-lasting abuse and a very complex process, presumably progressing with the duration of the adverse habit.

Adult↗
PubMed2001

A totally synthetic polyoxime malaria vaccine containing Plasmodium falciparum B cell and universal T cell epitopes elicits immune responses in volunteers of diverse HLA types.

This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine in volunteers of diverse HLA types. The polyoxime, designated (T1BT(*))(4)-P3C, was constructed by chemoselective ligation, via oxime bonds, of a tetrabranched core with a peptide module containing B cell epitopes and a universal T cell epitope of the Plasmodium falciparum circumsporozoite protein. The triepitope polyoxime malaria vaccine was immunogenic in the absence of any exogenous adjuvant, using instead a core modified with the lipopeptide P3C as an endogenous adjuvant. This totally synthetic vaccine formulation can be characterized by mass spectroscopy, thus enabling the reproducible production of precisely defined vaccines for human use. The majority of the polyoxime-immunized volunteers (7/10) developed high levels of anti-repeat Abs that reacted with the native circumsporozoite on P. falciparum sporozoites. In addition, these seven volunteers all developed T cells specific for the universal epitope, termed T(*), which was originally defined using CD4(+) T cells from protected volunteers immunized with irradiated P. falciparum sporozoites. The excellent correlation of T(*)-specific cellular responses with high anti-repeat Ab titers suggests that the T(*) epitope functioned as a universal Th cell epitope, as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes. The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic, multicomponent synthetic vaccines for malaria, as well as for other pathogens.

Adult↗
PubMed2001

Inhibition of the I(h) current in isolated peripheral nerve: a novel mode of peripheral antinociception?

Although the alpha2-adrenergic agonist clonidine has been shown to promote peripheral antinociception, its mechanism of action has not yet been clearly elucidated. By the use of the sucrose-gap method, we have shown that in C fibers of the rabbit vagus nerve, clonidine at micromolar concentrations enhances activity-dependent hyperpolarizations generated by the Na+-K+ pump during and after repetitive stimulation. Similar results were obtained with 10 microM of ZD 7288, a specific blocker of the hyperpolarization-activated cation current (I(h)) and with 2 mM of Ba2+ that blocks the inwardly rectifying potassium current (I(KIR)). Furthermore, clonidine had no added effect on the ZD 7288-induced response, whereas it produced a marked enhancement of Ba2+induced response. From these results, it can be concluded that clonidine enhances activity-dependent hyperpolarization by inhibiting the current I(h). We propose that clonidine, by increasing the threshold for initiating the action potential, induces a slowing or block of conduction and that this mechanism is the origin of the clonidine-induced antinociception. Finally, this study suggests a novel role for inwardly rectifying hyperpolarization-activated conductances in peripherally mediated antinociception.

Action Potentials↗
PubMed2001

beta-lactam derivatives as enzyme inhibitors: carboxy peptidyl derivatives of (S)-4-oxoazetidine-2-carboxylate as peptidomimetics.

4-Oxoazetidine-2-carboxylic acid, protected at the nitrogen by silyl groups, was coupled with amino acid and oligopeptide esters. Desilylation and deprotection of the amino acid residues yielded the free beta-lactam peptides. Structure and properties were elucidated by spectroscopic methods and discussed. Some selected compounds were tested as fibrinogen inhibitors and for thrombocyte aggregation. None of the compounds showed any activity up to a concentration of 10(-5) Mol/l. Some other compounds exhibited a weak inhibitory activity against elastase (PPE).

Enzyme Inhibitors↗
PubMed2001

Magnetic resonance imaging and miniarthroscopy of metacarpophalangeal joints: sensitive detection of morphologic changes in rheumatoid arthritis.

OBJECTIVE: To evaluate and characterize magnetic resonance imaging (MRI) findings in the metacarpophalangeal (MCP) joints of rheumatoid arthritis (RA) patients macroscopically, using miniarthroscopy (MA; needle arthroscopy). METHODS: The second MCP joint of the dominant hand of 22 RA patients (13 with various RA activities/stages; 9 with early RA [< or = 1.5 years' duration]) was examined by MRI followed by MA. Findings were evaluated by standardized semiquantitative measures of synovial and bony pathologic changes of the MCP joint, and were compared with the clinical and conventional radiologic findings. RESULTS: Erosions and pre-erosions were detected in 17 of 22 patients by MRI; 2 of the other 5 patients (all early RA) displayed bony changes on MA. All 10 joints with pre-erosions on MRI (grade I bony alterations on MRI) exhibited significant cartilaginous and bony pathology on MA. Synovial membrane pathology was detected in all but 1 patient by MRI and in all patients by MA, although findings of plain radiography were normal in 6 of the 22 patients and another 9 patients had a Larsen score of 1. Semiquantitative analysis of synovial findings of MRI revealed gadolinium diethylenetriaminepentaacetic acid enhancement as a significant marker of macroscopically varied synovial vascularity and hyperemia, both of which strongly correlated with clinical activity (as measured by the Disease Activity Score). The extent of synovitis/synovial proliferation shown by MA and MRI were significantly correlated with each other, but not with any other activity or damage parameter analyzed. CONCLUSION: In RA, both MRI and MA findings support early detection and staging of synovial changes. Ongoing longitudinal studies are aimed at evaluating the value of synovial proliferation as visualized by both methods.

Adult↗
PubMed2001

Parental medical neglect in the treatment of adolescents with anorexia nervosa.

OBJECTIVE: Although childhood sexual abuse has been a frequent focus of research on eating disorders, other forms of maltreatment have been less commonly reported. Parental medical neglect is examined in this study as having serious consequences for the treatment and prognosis of patients with anorexia nervosa. METHOD: Two case studies illustrate parental interference with treatment in which Child Protective Services (CPS) had to be involved in compliance with state law. Two adolescent females who were admitted for treatment for anorexia nervosa are presented. RESULTS: In both cases, the parents refused to comply with the recommendations of the treatment team, placing their children's health in jeopardy. In compliance with reporting guidelines, CPS was notified in both cases. CONCLUSIONS: Clinicians who treat minors with anorexia nervosa must consider parental compliance with treatment. Indications for the involvement of CPS are outlined. Optimally, this notification can ensure that the patient and family receive the requisite treatment.

Adolescent↗
PubMed2001

Concomitant twice-a-day radiotherapy and chemotherapy in unresectable head and neck cancer patients: A long-term quality of life analysis.

BACKGROUND: The purpose of this study is to make a comparative analysis between acute toxicity with late toxicity. This study is based upon a French quality of life (QoL) questionnaire in a cohort of advanced head and neck (H&N) cancer patients treated by concomitant twice-a-day continuous radiotherapy with no acceleration and chemotherapy with cisplatin and 5-fluorouracil. METHODS: From September 1992 to November 1997, a prospective data bank of 91 patients was constituted. In November 1999, 31 patients were still alive and followed for more than 3 years. All patients had stage IV strictly unresectable squamous cell carcinoma of oropharynx or hypopharynx. A French specific H&N cancer QoL questionnaire was used at the end of radiotherapy and at the last date of follow-up of each patient (during 1999). p values reflect comparison of percentages obtained at the end of treatment with percentages at long-term follow-up. Statistical analysis was performed using chi(2) test (p <.05 considered as significant). Percentages obtained by the QoL questionnaire correspond to moderate-severe problems only. RESULTS: Twenty-nine of 31 (94%) patients participated in the QoL study. Acute treatment toxicities were severe with declines in virtually all QoL and functional domains. Globally, with an average long-term follow-up of 4.5 years (range 3-7 years after treatment), there is a statistical improvement in the following symptoms: dry mouth and sticky saliva (97% versus 55%, p <.05); tasting problems (35% versus 21%, not significant); swallowing problems (77% versus 36%, p <.05); and H&N pain (86% versus 9%, p <.05). Financial problems were not improved (21% versus 14%, not significant), and psychological problems (59% versus 5%) were statistically significant. Fourteen of 29 (48%) patients were drinking and 8 of 29 (28%) were smoking at long-term follow-up; at the diagnosis they were 86% and 90%, respectively. At long-term follow-up 22 of 29 presented good or very good QoL, and 25 of 29 said they had improved their initial QoL. CONCLUSION: The interest of twice-a-day radiotherapy with concomitant chemotherapy is to increase total radiotherapy equivalent dose without increasing late toxicity and also to improve locoregional control, survival, and long-term QoL/effectiveness ratio. Best supportive care is recommended to obtain both good QoL and cancer control in a long-term follow-up.

Adult↗
PubMed2001

Differential infectivity of two Pseudomonas species and the immune response in the milkweed bug, Oncopeltus fasciatus (Insecta: Hemiptera).

Pseudomonas aeruginosa and Pseudomonas putida show a profound differential infectivity after inoculation in Oncopeltus fasciatus. Whereas P. putida has no significant impact on nymphs, P. aeruginosa kills all experimental animals within 48 h. Both Pseudomonas species, however, induce the same four hemolymph peptides in O. fasciatus. Also injection of saline solution and injury induced these peptides. In general peptide induction was stronger in nymphs than in adult males. A significantly higher number of nymphs survived a challenge with P. aeruginosa when an immunization with P. putida preceded. The antibacterial properties of the hemolymph were demonstrated in inhibition experiments with P. putida. Two of the four inducible peptides (peptides 1 and 4) could be partially sequenced after Edman degradation and were compared with known antibacterial peptides. Peptide 1, of 15 kDa, showed 47.1% identity with the glycine-rich hemiptericin of Pyrrhocoris apterus. Peptide 4, of 2 kDa, had a 77.8% identity with the proline-rich pyrrhocoricin of P. apterus and a 76.9% identity with metalnikowin 1 of Palomena prasina. Peptides 2 and 3 are also small, with molecular weights of 8 and 5 kDa.

Amino Acid Sequence↗
PubMed2001

Mixed micelles containing lipophilic gadolinium complexes as MRA contrast agents.

Mixed micelles for MRA are multicomponent systems containing a phospholipid, a biocompatible non-ionic surfactant (e.g. Synperonic(R) F-108) and a lipophilic gadolinium complex. A variety of lipophilic gadolinium complexes were designed taking into account features such as: (i) nature of ligand (cyclic versus acyclic); (ii) lipophilic moiety; (iii) global charge of the complex; and (iv) nature of bond connecting the complex to the lipophilic moiety. All the lipophilic gadolinium complexes after formulation as mixed micelles show high relaxivities in water and in blood (rat). Mixed micelles containing gadolinium complexes bearing only one aliphatic chain cannot be used as MRA contrast agents because they have a high haemolytic effect. Furthermore, in rats they are quickly eliminated from the blood stream. These drawbacks are completely circumvented using gadolinium complexes bearing two aliphatic chains. Mixed micelles containing such complexes show high relaxivities, no haemolytic effect and long blood permanence. This makes them promising candidates as MRA contrast agents. However, elimination, which occurs exclusively through the liver, is not complete, even after 7 days. Complexes containing labile (e.g. ester) bonds between the lipophilic moieties and the chelate subunit are eliminated through both the liver and the kidneys. However, elimination is still not complete after 7 days.

Animals↗
PubMed2001

[Atkinson's retrobulbar anesthesia. A quality control study].

PURPOSE OF THE STUDY: Recognized local and systemic complications of retrobulbar anaesthesia (RA) are well known. The purpose of this study was to determine which clinical signs predict the success of the RA technique. METHODS: We prospectively investigated 500 consecutive patients scheduled for elective eye surgery for cataracts and for vitreoretinal procedures. Anaesthesia was administered using the Atkinson RA technique while for preoperative quality control, the following parameters were recorded: chemosis, eye motility, preservation of vision, active eyelid movement, and burning caused by disinfection. For analysis, a multidimensional model designed to be useful for forecasting results of the anaesthetic outcome was used. The RA was labeled as a "success" when no supplementary anaesthetics were required. "Partial success" was defined as an incomplete RA with supplementary subconjunctival anaesthetic requirement or an anaesthetic given in the form of eyedrops. In the case of "RA failure", the RA had to be repeated. RESULTS: The success rate for RA was higher for cataract operations than for glaucoma operations. The success rate was not associated with the choice of the local anaesthetic, the application of ocular, compression, or the anaesthetists and surgeons who performed the RA. Burning caused by disinfectant, lid opening and temporal eye motility were found not to be associated with a successful outcome. The presence of chemosis had no influence on the success of anaesthesia. CONCLUSIONS: The results of this study demonstrated that prognostic factors such as defined existing clinical signs, are early predictors of the success of the Atkinson RA.

Aged↗
PubMed2001

[Bone density and 25-OH vitamin D serum level in patients with systemic lupus erythematosus].

OBJECTIVE: To clarify the influence of vitamin D metabolism on bone mineral density (BMD) or bone metabolism in patients with systemic lupus erythematosus (SLE). METHODS: 57 consecutive patients in our department (mean age 33.9 years, 44 female, 13 male) were studied. BMD was measured with dual-X-ray absorptiometry at the lumbar spine and femoral neck. Biochemical investigation of bone metabolism included measurement of vitamin D metabolites, intact parathyroid hormone (PTH), serum osteocalcin und urinary pyridinoline-crosslink excretion. RESULTS: 25 patients had 25-OH cholecalciferol serum values below the normal range after adjustment for seasonal changes; 9 patients were severely vitamin D depleted with 25-OH vitamin D serum values below 5 ng/ml. Low 25-OH-vitamin D was significantly associated with high disease activity. Mean 1.25 (OH)2-vitamin D, PTH, osteocalcin and crosslink excretion were in the normal range. Thirty-six patients had normal BMD; 5 patients had osteoporosis according to WHO diagnosis criteria. No correlation of biochemical parameters of bone metabolism with BMD was found. CONCLUSION: Severe vitamin D depletion was common in this group of patients with SLE even after adjustment for seasonal variations, especially in patients with high disease activity. Therefore, D-hypovitaminosis should be included in the differential diagnosis in patients with SLE presenting with low bone mass.

Adult↗