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Biomedical subjects

M Lutz

Publications and source records attributed to M Lutz.

At least 19 recordsLinked to original sources
PubMed1991

Anti-CD2 antibodies induce T cell unresponsiveness in vivo.

The CD2 receptor functions as an adhesion and signal molecule in T cell recognition. Multimeric binding of CD2 on T cells to its physiologic ligand LFA-3 on cognate partner cells in vitro efficiently augments the antigen-specific T cell signal delivered by the T cell receptor/CD3 complex. The precise contribution of the antigen-nonspecific CD2-LFA-3 interactions to T cell immune responses in vivo, however, has been difficult to assess. Here we analyzed the role of CD2 in the murine immune response using a nondepleting anti-CD2 monoclonal antibody that induces a marked, reversible modulation of CD2 expression on murine T and B cells in situ. This modulation is dose and time dependent, specific for CD2, and does not require the Fc portion of the antibody. Anti-CD2 antibodies [rat IgG1 or F(ab')2] significantly inhibit the CD4+ T cell-mediated response to hen egg lysozyme and the cytotoxic CD8+ T cell response to a syngeneic tumor cell line. In both cases, anti-CD2 antibodies are only effective when administered before or within 24 h after antigen priming. The suppression of the antitumor response corresponds to a sixfold reduction of specific cytotoxic T lymphocyte precursor cells and results in the abrogation of protective antitumor immunity. Anti-CD2 antibodies also affect the humoral immune response to oxazolone: the isotype switch from specific IgM to IgG1 antibodies is delayed, whereas the IgM response is unaltered. In addition, a single antibody injection results in sustained polyclonal unresponsiveness of T cells irrespective of antigen priming and CD2 modulation. These results document that CD2-mediated signals induce a state of T cell unresponsiveness in vivo.

Animals↗
PubMed1991

Primary donor structure and interactions in bacterial reaction centers from near-infrared Fourier transform resonance Raman spectroscopy.

Preresonance Raman and resonance Raman spectra of the primary donor (P) from reaction centers of the Rhodobacter (Rb.) sphaeroides R26 carotenoidless strain in the P and P+ states, respectively, were obtained at room temperature with 1064-nm excitation and a Fourier transform spectrometer. These spectra clearly indicate that the chromophore modes are observable over those of the protein with no signs of interference below 1800 cm-1. The chromophore modes are dominated by those of the bacteriochlorophylls (BChl a), and it is estimated that, in the P state, ca. 65% of the Raman intensity of the BChl a modes arises from the primary donor. This permits the direct observation of a vibrational spectrum of the primary donor at preresonance with the excitonic 865-nm band. The Raman spectrum of oxidized reaction centers in the presence of ferricyanide clearly exhibits bands arising from a BChl a+ species. The magnitude of the frequency shift of a keto carbonyl of neutral P from 1691 to 1717 cm-1 upon P+ formation strongly suggests that one BChl molecule in P+ carries nearly the full +1 charge. Our results indicate that the unpaired electron in P.+ does not share a molecular orbital common to the two components of the dimer on the time scale of the resonance Raman effect (ca. 10(-13) s).

Fourier Analysis↗
PubMed1991

Resonance Raman characterization of Rhodobacter sphaeroides reaction centers bearing site-directed mutations at tyrosine M210.

Resonance Raman (RR) spectroscopy and low-temperature absorption spectroscopy have been used to investigate the structural changes in the reaction centers (RCs) of Rhodobacter sphaeroides induced by site-specific mutations on the tyrosine (Y) M210 residue. RCs in which Y M210 has been genetically replaced with phenylalanine (F) or leucine (L) exhibit a 5-fold decrease in their primary electron-transfer kinetics (Finkele et al., 1990). The general similarity of RR spectra of the wild-type RCs as compared to those of the two mutant RCs indicates that no significant global structural changes occur upon mutation at the level of any of the six bacteriochlorin pigments. In the RR spectra of the two mutant RCs there is a conspicuous absence of contributions from the BPheM prosthetic group, which is interpreted in terms of a change in the resonance enhancement conditions of this chromophore. Low-temperature adsorption spectroscopy reveals marked shifts in the Qx absorption band of BPheM. This shift is interpreted as arising from a destabilization of the protein in the vicinity of BPheM and accounts for the change in resonance condition for this chromophore in its RR contributions. As well, there is a 3-nm red shift of the Qy absorption band of the BChls from 803 to 806 nm for the mutant RCs. Difference RR spectra yielding structural information concerning, selectively, the primary donor (P) indicate that the structure of the P binding pocket is conserved for these mutant RCs. The tyrosine M210 is not observed to be engaged in a hydrogen bond with either of the acetyl or keto carbonyls of P.

Kinetics↗
PubMed1991

In vitro studies on drug interaction of ifosfamide and ACNU in primary and metastatic human brain tumours.

Combination chemotherapy is widely employed in clinical oncology; however, there is no generally accepted model to evaluate individual tumour susceptibility to a given drug combination protocol. We therefore investigated the drug interaction of ifosfamide (4-hydroxyperoxy-ifosfamide) and ACNU in a recently developed in vitro model of paired sequential combination chemotherapy in primary and metastatic malignant brain tumours. A long-term standard [6,3-3H]-thymidine-incorporation assay, employing a liquid scintillation counting protocol, was selected to assess the drug sensitivity of human tumours. In vitro drug exposures were derived from correlating in vivo-(systemic and CNS) and in vitro-pharmacokinetic drug parameters. In combination experiments tumour cells were treated sequentially by two drugs in both sequences: drug exposures were calculated for 2 h with a 1-h drug-free interval in between. "Cut-off" concentrations (maximum in vitro exposure doses) were calculated as 1.74 microM (for primary CNS tumours: 0.58 microM) for ifosfamide and 5.4 microM (for primary CNS tumours: 1.33 microM) for ACNU. Dose/response relations were derived from isotope incorporation rates after cells had grown for approximately five population doubling times. Combination isoboles were plotted after drug doses had been transformed into "equieffective doses", enabling comparison of drug combination effects. In all three glioblastomas (with CNS exposure dose) an additive or supra-additive effect could be observed in either sequence (in one tumour a biphasic additive isobole was found for both sequences). Out of three bronchial carcinomas (small-cell type, brain metastases) in two non-identical sequences a supra-additive effect was observed in two tumours, with antagonistic effects in the third tumour. In all three malignant melanomas and in one renal carcinoma antagonistic effects were observed, whereas in a second renal carcinoma supra-additive effects were demonstrated for both sequences. We conclude that drug combination chemotherapy effects at the cellular level may be extremely heterogeneous.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Structure of the primary electron donor in photosystem I: a resonance Raman study.

Low-temperature resonance Raman (RR) spectra have been obtained at resonance with the Soret transition of chlorophyll a in photosystem I particles containing large amounts either of the triplet state of P700 or of its radical cation state. Subtracting these spectra from those of resting reaction centers yielded RR spectra of P700 in its neutral, ground state. These spectra arise from two distinct chlorophyll a molecules differing by the strengths of the bonding interactions assumed by their keto carbonyl groups, the stretching frequencies of which are found at 1655 and 1675 cm-1. The present results rule out previous hypotheses that P700 might have consisted of a single, chemically modified chlorophyll a molecule. Neither of the bonding interactions assumed by the keto carbonyls of the P700 chlorophylls most probably involves chlorophyll-chlorophyll bridging through water molecules, as surmised in the so-called special pair models, but likely consists of H bonds with distinct protein sites. The magnesium atoms of the two P700 chlorophylls are 5-coordinated. Hence, the structural model of P700 provided by the present data is qualitatively the same, in terms of bonding interactions, as that currently accepted for the bacterial primary donor.

Binding Sites↗
PubMed1990

Histologic sampling requirements in ovarian carcinoma: a review of 51 tumors.

In a review of 29 serous and 22 mucinous adenocarcinomas of the ovary, we quantitated the various histologic patterns seen in these neoplasms in order to document histologic variability and assess current anecdotal recommendations (one section per 1-2 cm of maximum tumor diameter) for adequate histologic sampling of epithelial ovarian neoplasms. Mucinous carcinomas showed more histologic variation than serous carcinomas, but both showed substantial portions with benign or borderline histology in many neoplasms. One serous and one mucinous carcinoma were likely to have been classified as borderline tumors if only current sampling recommendations had been followed. The remaining adenocarcinomas were adequately sampled by current standard practice. The two tumors in question had unusual clinical and histological features which prompted additional sampling. Caution is particularly warranted when initial frozen section sampling shows features of borderline tumor histology or low grade epithelial atypia, especially in mucinous epithelial neoplasms where histologic variability is greatest.

Adenocarcinoma, Mucinous↗
PubMed1990

Occlusive vascular stapling in a canine inferior vena cava model.

A canine model for inferior vena cava resection was devised to study the biomechanical and clinical applications of the cartridge stapler, which applies a triple staggered staple line. Eighteen mongrel dogs were subjected to subhepatic, suprarenal inferior vena cava occlusion with excision of the excluded segment. At 1 hour, six dogs were killed and inferior vena cava sizes and pressures were measured. All staple lines were intact. The inferior vena cava bursting pressure was 150 to 300 mm Hg. Ten dogs survived to 6 weeks and underwent repeat laparotomy with excision and measurement of the remaining inferior vena cava. Mean diameter was 1.9 cm. No evidence of staple line leakage was found despite chronic pressures to 39 cm H2O: median static bursting pressures were 250 mm Hg. Vein wall thickness of greater than 0.24 mm were all satisfactorily stapled. Histologic examination revealed normal reendothelialization, with improved healing at higher chronic pressures. No evidence of inflammation at the staple line or foreign body reaction was found. We conclude that a triple staple line provides secure, rapid venous occlusion that can withstand supraphysiologic stresses immediately and at 6 weeks.

Animals↗
PubMed1990

Efficacy of concomitant early summer treatment with fenbendazole and clorsulon against Fasciola hepatica and gastrointestinal nematodes in calves in Louisiana.

The efficacy, safety, and compatibility of fenbendazole (FBZ) and clorsulon (CLN) were tested after oral administration of label recommended and of higher (5x) dosage rates to calves naturally infected with gastrointestinal nematodes and Fasciola hepatica. Results for 42 calves allotted to 4 treatment groups indicated a similar efficacy against mature F hepatica by FBZ (5 mg/kg of body weight) and CLN (7 mg/kg) in a combined oral suspension, compared with CLN (7 mg/kg) alone (100 vs 99% reduction). A lesser efficacy was observed against immature flukes (88.6 and 84.9% reduction, respectively). Calves given 25 mg of FBZ/kg and 35 mg of CLN/kg had nearly complete reduction of both mature (99.6%) and immature flukes (99.1%). Fasciola egg counts were reduced by greater than 99.5% in all treated groups. Against Ostertagia ostertagi, the percentage of efficacy of the combined FBZ (5 mg/kg) and CLN (7 mg/kg) treatment was 94.3% against adults and 81.3% against inhibited larvae. Efficacy against all other nematodes was 100%, except against Cooperia spp adults (98.3%) and immature Oesaphagostomum radiatum (88.0%). At 5 x dosage rates for FBZ and CLN, percentage of removal of adults and inhibited larvae of O ostertagi was 99.3 and 99.0%, respectively, and 99 to 100% for other nematodes. Results indicate that FBZ and CLN are compatible when mixed together and administered as an oral suspension to cattle and that the efficacy is similar to that of the drugs individually. On the basis of further results, we suggest that summer treatment may be superior in preventive value for gastrointestinal nematodes and F hepatica, compared with spring treatment, because of seasonal infection dynamics of the major cattle parasites in Louisiana.

Animals↗
PubMed1989

Structure of spheroidene in the photosynthetic reaction center from Y Rhodobacter sphaeroides.

The structure of the reaction center of Y Rhodobacter sphaeroides has been solved at 3 A resolution, using the atomic coordinates of the reaction center from the carotenoidless mutant R26 Rhodobacter sphaeroides. The structure has been refined by a stimulated annealing with the computer program X-PLOR, leading to a crystallographic R factor of 0.22 using reflections between 8 and 3 A. The spheroidene molecule which is bound to the Y reaction center has been fitted in the electron density map as a 15-cis isomer with a highly asymmetric structure. The cis-bond is located at proximity from ring 1 of the accessory bacteriochlorophyll on the inactive M side. The nature of the cis-bond was confirmed by resonance Raman spectra obtained from Y reaction center crystals. The structure of spheroidene in Y reaction center is compared to that proposed for 1,2-dihydroneurosporene in Rhodopseudomonas viridis reaction center crystals.

Bacterial Proteins↗
PubMed1989

Flavin and heme structures in lactate:cytochrome c oxidoreductase: a resonance Raman study.

Resonance Raman spectra of Hansenula anomala L-lactate:cytochrome c oxidoreductase (or flavocytochrome b2), of its cytochrome b2 core, and of a bis(imidazole) iron-protoporphyrin complex were obtained at the Soret preresonance from the oxidized and reduced forms. Raman contributions from both the isoalloxazine ring of flavin mononucleotide (FMN) and the heme b2 were observed in the spectra of oxidized flavocytochrome b2. Raman diagrams showing frequency differences of selected FMN modes between aqueous and proteic environments were drawn for various flavoproteins. These diagrams were closely similar for flavocytochrome b2 and for flavodoxins. This showed that the FMN structure must be very similar in both types of proteins, despite their very different proteic pockets. However, the electron density at this macrocycle was found to be higher in flavocytochrome b2 than in these electron transferases. No significant difference was observed between the heme structures in flavocytochrome b2 and in cytochrome b2 core. The porphyrin center-N(pyrrole) distances in the oxidized and reduced heme b2 were estimated to be 1.990 and 2.022 A from frequencies of porphyrin skeletal modes, respectively. The frequency of the vinyl stretching mode of protoporphyrin was found to be very affected in resonance Raman spectra of flavocytochrome b2 and of cytochrome b2 core (1634-1636 cm-1) relative to those observed in the spectra of iron-protoporphyrin [bis(imidazole)] complexes (1620 cm-1). These specificities were interpreted as reflecting a near coplanarity of the vinyl groups of heme b2 with the pyrrole rings to which they are attached. The low-frequency regions of resonance Raman indicated that the iron atoms of the four hemes b2 are in the porphyrin plane whatever their oxidation state. The histidine-Fe-histidine symmetric stretching mode was located at 205 cm-1 in the spectra of flavocytochrome b2 and of cytochrome b2 core. It was insensitive to the iron oxidation state and indicated strong Fe-His bonds in both states.

Flavin Mononucleotide↗
PubMed1988

Dialysis in the management of pregnant patients with renal insufficiency.

Successful pregnancy in patients on dialysis is uncommon because of a high rate of infertility and complications. The use of hemodialysis to manage pregnant patients needing dialysis has been well reported. However, to our knowledge, only 2 previous cases of pregnant patients using chronic ambulatory peritoneal dialysis (CAPD) have been reported. We discuss 14 pregnancies in 13 women in whom dialysis was used in the management of their pregnancies. Ten pregnancies were successful. Included are 5 successful pregnancies out of 8 managed with CAPD or chronic cycling peritoneal dialysis (CCPD). In comparing the cases managed with CAPD to those managed with hemodialysis, CAPD seems to offer several advantages. These include a more constant biochemical and extracellular environment for the fetus, higher hematocrit levels, infrequent episodes of hypotension, and no heparin requirement. In addition, intraperitoneal insulin facilitates the management of blood glucose in diabetics, and intraperitoneal magnesium facilitates the management of premature labor. Infection, loss of intraperitoneal volume, and loss of peritoneal clearances for solutes and water were not found to be problems.

Adult↗
PubMed1987

Effect of structured dietary fiber on bioavailability of amoxicillin.

The effect of structured dietary fiber on the bioavailability of amoxicillin (AMX) was evaluated. Ten healthy volunteers ingested one of two isocaloric, isonitrogenous diets providing 7.8 gm/day (diet I) and 36.2 gm/day (diet II) of structured fiber for 3 days. Then they ingested one tablet (500 mg) AMX after breakfast. The other diet was administered for an additional 3 days and the study was repeated. Plasma and urinary AMX concentrations were measured at 9 and 24 hours, respectively, by a microbiologic technique. An open one-compartment model was used for pharmacokinetic analysis. AMX was absorbed more slowly when ingested with diet I than with diet II: the absorption rate constant was 1.04 +/- 0.37 and 1.75 +/- 0.75 (P less than 0.05); lag time for absorption was 0.34 +/- 0.13 hours and 0.29 +/- 0.11 hours (P less than 0.05). The first-order rate constant and elimination half-life were similar. Bioavailability was higher with diet I: the AUC was 12.17 +/- 3.04 vs. 9.65 +/- 2.64 micrograms/ml/hr with diet II (P less than 0.05). A higher content of dietary fiber increased AMX absorption rate and decreased the amount of drug absorbed.

Absorption↗
PubMed1985

Fibronectin plasma levels after cadaver kidney transplantation.

The fibronectin plasma levels of 17 patients undergoing cadaver kidney transplantation were determined serially in the postoperative course using laser nephelometry. While 9 patients retained their grafts (group A), the grafts of 8 patients had to be removed (group B), mainly due to rejection, 3 patients had severe infections. In both groups a significant drop of the plasma fibronectin occurred after surgery. There were no significant differences between the two groups in the mean fibronectin levels. After the initial drop the group A patients exhibited rising values leading to a stable level. Progressively declining fibronectin plasma concentrations were found in 2 of 3 severely infected patients. Fluctuating values were found in 3 group B patients without a clear correlation to the rejection crises or the kidney function. The data suggest that the fibronectin plasma level does not seem to be a prognostic marker for graft rejection. But it might be useful in the important and often difficult differentiation between rejection and infection.

Adult↗
PubMed1985

Structural characterization of high 800 nm-absorbing light-harvesting complexes from Rhodospirillales from their resonance Raman spectra.

Resonance Raman spectroscopy provided evidence that high 800 nm-absorbing antennae from Rhodopseudomonas (Rps.) acidophila and Rps. palustris have similar structures around their dweller bacteriochlorophylls. These host-site structures are different from those of B 850-800 complexes from Chromatiaceae, which also exhibit a high absorbance at 800 nm. As also shown by previous biochemical data, these complexes might be stoichiometrically different from other antenna complexes, having one more BChl per minimal size unit of protein. A new classification of B 850-800 complexes is proposed, on the basis of resonance Raman and biochemical data: this classification distinguishes a class of B 850-800 S (involving the B 850-800 complexes from sulfur purple bacteria), two classes of B 850-800 NS (involving the B 850-800 complexes from non sulfur purple bacteria) and a class of H 800 complexes (involving the B 850-800 complexes from non sulfur purple bacteria exhibiting a high absorbance at 800 nm).

Bacterial Proteins↗
PubMed1983

Synthetic perfusate for kidney preservation. Its use in 72-hour preservation of dog kidneys.

Hydroxyethyl starch (HES) was used as the sole colloid for oncotic support in a perfusate for successful (12 of 12 survivors) 72-hour kidney preservation by hypothermic-pulsatile perfusion. Posttransplant renal function was consistently better than that obtained with other perfusates commonly used in continuous perfusion preservation. Often the posttransplant serum creatinine levels rose to only 1.6 mg/dL and rapidly returned to normal (1.0 mg/dL). The perfusate included, in addition to HES, gluconate as the major anion in place of chloride. Perfusate containing high levels of potassium produces results equal to those with high levels of sodium. This is, to our knowledge, the first report of consecutive successful 72-hour preservation of canine kidneys using a purely synthetic perfusate devoid of animal-derived protein for colloid oncotic support.

Animals↗