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N Friedman

Publications and source records attributed to N Friedman.

At least 91 records · Page 5Linked to original sources
PubMed1987

Factors affecting the C = N stretching in protonated retinal Schiff base: a model study for bacteriorhodopsin and visual pigments.

Factors affecting the C = N stretching frequency of protonated retinal Schiff base (RSBH+) were studied with a series of synthetic chromophores and measured under different conditions. Interaction of RSBH+ with nonconjugated positive charges in the vicinity of the ring moiety or a planar polyene conformation (in contrast to the twisted retinal conformation in solution) shifted the absorption maxima but did not affect the C = N stretching frequency. The latter, however, was affected by environmental perturbations in the vicinity of the Schiff base linkage. Diminished ion pairing (i.e., of the positively charged nitrogen to its anion) achieved either by substituting a more bulky counteranion or by designing models with a homoconjugation effect lowered the C = N stretch energy. Decreasing solvation of the positively charged nitrogen leads to a similar trend. These effects in the vicinity of the Schiff base linkage also perturb the deuterium isotope effect observed upon deuteriation of the Schiff base. The results are interpreted by considering the mixing of the C = N stretching and C = N-H bending vibration. The C = N mode is shifted due to electrostatic interaction with nonconjugated positive charges in the vicinity of the Schiff base linkage, an interaction that does not influence the isotope effect. Weak hydrogen bonding between the Schiff base linkage in bacteriorhodopsin (bR) and its counteranion or, alternatively, poor solvation of the positively charged Schiff base nitrogen can account for the C = N stretching frequency of 1640 cm-1 and the deuterium isotope effect of 17 cm-1 observed in this pigment.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriorhodopsins↗
PubMed1987

The influences of fear, anxiety, and depression on the patient's adaptive responses to complete dentures. Part I.

Loss and body image can result in anxiety, depression, or both and can affect a patient's adaptive capacity to accept edentulism and complete dentures. A specific classification system has been presented to identify responses by individuals who are made edentulous. Three types of maladaptive responses are considered as probable consequences of fear, anxiety, and depression associated with tooth loss and complete dentures. In maladaptive class 1, the patient adapts physically but is maladaptive psychologically; thus suffering some impairment of the quality of life. In maladaptive class 2, the so-called "difficult patient" is maladaptive physically and psychologically and keeps the doctor involved technically and emotionally for a protracted period of time. The maladaptive class 3 patient collapses with the loss of teeth. Physical and emotional maladaptibility is accompanied by much suffering and social withdrawal.

Adaptation, Psychological↗
PubMed1986

The roles of intracellular glutathione in antineoplastic chemotherapy.

Glutathione is a sulfhydryl containing tripeptide that participates in detoxification of xenobiotic compounds, including the alkylating agents melphalan, cyclophosphamide, and BCNU. The role of glutathione in the detoxification of these compounds, both in terms of initial tumor response, and drug-induced resistance to these alkylating agents is examined. Since glutathione disulfide and glutathione are a pivotal redox pair, the modulation of intracellular glutathione levels is shown to change the cytotoxicity of drugs dependent on the redox cycle, such as adriamycin and bleomycin, as well as the oxygen dependent drug neocarzinostatin. Areas of further research are discussed.

Animals↗
PubMed1986

In vivo modulation of glutathione by buthionine sulfoximine: effect on marrow response to melphalan.

The effect of giving buthionine sulfoximine (BSO), 0.0265 g/mouse (6 mM), at 12 and 6 hr before treatment with melphalan--0.0 mg, 3 mg, 6 mg, and 9 mg/kg, was studied in C3H mice, and was compared with control groups that received normal saline 12 and 6 hr before identical melphalan treatment. BSO treatment resulted in depletion of GSH levels in bone marrow, liver, and muscle to 65, 13, and 41% of control levels, respectively. Hematological toxicity was assessed by measurement of CFU-S survival and peripheral white cell counts. CFU-S survival decreased with increasing doses of melphalan, but no difference was observed with BSO pre-treatment. Likewise, WBC counts following melphalan 9 mg/kg, were similar irrespective of BSO pre-treatment. These data suggest that the marrow toxicity seen with melphalan is not worsened by pre-treatment with BSO and that if tumors can be pre-sensitized with BSO, there may be a clinical role for melphalan/BSO drug combination.

Animals↗
PubMed1986

Inhibition of the protective effect of cyclophosphamide by pre-treatment with buthionine sulfoximine.

Low dose cyclophosphamide (CTX) is protective against a subsequent challenge with a lethal dose of the same drug administered 5 days later. At the time of maximal protection, elevation of glutathione (GSH) and glutathione transferase (GST) levels are detectable in the bone marrow of pre-treated animals. Elevation of GSH levels in the bone marrow was inhibited with the use of D,L-buthionine-S,R-sulfoximine (BSO), and this resulted in loss of the protective effect of CTX pre-treatment. In contrast, the overshoot in GST levels observed in these animals was not affected by BSO therapy. Bone marrow GSH levels in animals treated with BSO alone were minimally depleted (68% of control); whereas, animals pre-treated with CTX followed by BSO exhibited a greater reduction in GSH levels (47% of control). These results suggest that GSH is important in the protective effect afforded by low dose CTX pre-treatment and that the elevation of GSH levels observed is the result of a rebound synthetic process. In CTX pre-treated animals, BSO treatment resulted in greater than predicted depletion in GSH levels, and, therefore, caution is recommended with the potential use of combinations of BSO and cytotoxic drugs in the presence of a regenerating bone marrow.

Animals↗
PubMed1986

Controlling the pKa of the bacteriorhodopsin Schiff base by use of artificial retinal analogues.

Artificial bacteriorhodopsin pigments based on synthetic retinal analogues carrying an electron-withdrawing CF3 substituent group were prepared. The effects of CF3 on the spectra, photocycles, and Schiff base pKa values of the pigments were analyzed. A reduction of 5 units in the pKa of the Schiff base is observed when the CF3 substituent is located at the C-13 polyene position, in the vicinity of the protonated Schiff base nitrogen. The results lead to the unambiguous characterization of the (direct) titration of the Schiff base in bacteriorhodopsin and to the conclusion that the deprotonation rate of the Schiff base during the photocycle (i.e., the generation of the M412 intermediate) is determined by a structural change in the protein.

Aldehydes↗
PubMed1986

Serum amyloid A (SAA) variations in patients with cancer: correlation with disease activity, stage, primary site, and prognosis.

Serum amyloid A (SAA) was determined in 160 patients with cancer. Active disease was associated with high titre compared with the titre in non-active condition (31.8 v 5.8 micrograms/ml, respectively; p = 0.0002). SAA value showed a direct correlation with the stage of the disease: it was lowest at stages 1 and 2 and highest at the metastatic stage 4 (stage 1 v 4, p = 0.001; stage 2 v 3, p = 0.05). Cancers of the lung and unknown primary site were characterised by highly increased SAA concentration. Initial SAA value had prognostic significance: a value below 10 micrograms/ml correlated with survival advantage, whereas a higher initial value indicated a greater likelihood of a poor outcome (actuarial survival analysis p less than 0.001). When stage was accounted for, initial SAA value had significant prognostic bearing on survival of patients with advanced disease (stages 3 and 4) but not on that of patients with limited disease (stages 1 and 2). Serial testing showed good concordance between changes in SAA titre and clinical course.

Amyloid↗
PubMed1986

Selective modulation of glutathione levels in human normal versus tumor cells and subsequent differential response to chemotherapy drugs.

Cellular glutathione (GSH) levels were found to be 7-fold higher in a human lung adenocarcinoma cell line (A549) than in a normal human lung fibroblast line (CCL-210). Differential modulation of cellular GSH was explored in these cell lines by (a) stimulation of GSH synthesis by oxothiazolidine-4-carboxylate (OTZ) and (b) inhibition of GSH synthesis by buthionine sulfoximine (BSO). In the tumor cell line, OTZ treatment had no effect; however, GSH levels of 140-170% of control were achieved in the normal fibroblast line. With BSO, the normal cell line was depleted of GSH at a faster relative rate than with the tumor line. Within 7 h, 5% GSH remained in the CCL-210 line while approximately 40% GSH remained in the A549 line. Survival response of normal versus tumor cell lines to selected chemotherapy drugs was compared following modulation of GSH levels. OTZ pretreatment of the A549 line provided no protection to a 1-h exposure to melphalan, cisplatin, or bleomycin; however, OTZ pretreatment of CCL-210 elevated GSH and provided protection to melphalan, cisplatin, and bleomycin (protection ratios at 5% survival of 1.2, 1.4, and 1.4, respectively). Neocarzinostatin toxicity in the normal CCL-210 line pretreated with BSO was greatly reduced (protection ratio at 50% survival = 5.0). The same BSO treatment to A549 cells (40% GSH remaining) yielded a similar survival curve to control cells. These studies demonstrate that selective differential chemotherapy responses of normal versus tumor cells is possible by manipulating the GSH synthetic cycle. Should basic phenotypic differences with regard to reductive capacity exist in vivo, such manipulation in GSH levels might yield a therapeutic gain for carefully selected chemotherapy drugs.

Antineoplastic Agents↗
PubMed1985

Calcification of entheses associated with X-linked hypophosphatemic osteomalacia.

We undertook a retrospective analysis of 26 patients with X-linked hypophosphatemic osteomalacia (or rickets), whose ages ranged from 1 to 62 years and who were from 11 different kindreds, to determine the prevalence and clinical characteristics of a unique disorder of the entheses (tendons, ligaments, and joint capsules). We found a generalized involvement of the entheses, with exuberant calcification of tendon and ligament insertions and of joint capsules, in 69 per cent of the subjects. The prevalence and extent of disease increased with age but were not correlated with sex. Commonly affected sites included the hand and sacroiliac joints. Histologic evaluation in a selected patient revealed intratendinous lamellar bone but no inflammatory cells. Our observations indicate that this disorder is an integral part of X-linked hypophosphatemic osteomalacia and exhibits clinical, radiographic, and histologic characteristics that differentiate it from degenerative disorders of these tissues and seronegative spondyloarthropathies.

Adolescent↗
PubMed1985

Depletion of cellular glutathione by exogenous spermine in V79 cells: implications for spermine-induced hyperthermic sensitization.

The relationship between spermine-induced thermosensitization and modulation in the cellular redox state as measured by glutathione levels was studied using Chinese hamster V79 cells. Marked cellular glutathione depletion was observed for cells treated with exogenous 1 mM spermine at 37 degrees C or 43 degrees C. Glutathione depletion and thermal sensitization by spermine were found to be cell density dependent with maximum depletion and sensitization observed at low cell densities. These findings are discussed in the context that treatment of cells with exogenous polyamines such as spermine can result in cellular oxidative stress which may in part contribute to spermine-induced thermal sensitization.

Animals↗
PubMed1984

Alteration of bleomycin cytotoxicity by glutathione depletion or elevation.

In part, some of the cytotoxicity of bleomycin may be lessened or enhanced by modulation of glutathione (GSH) concentrations. Enhancement of bleomycin cytotoxicity was observed when GSH levels were low and protection was observed when GSH levels were elevated. Since H2O2 is one of the reactive species produced by bleomycin catalyzed oxygen activation, we studied the effects of H2O2 exposure after GSH depletion. H2O2, like bleomycin, shows enhanced cytotoxicity in GSH depleted cells. It has been proposed that bleomycin cytotoxicity requires reducing equivalents from non-protein bound thiols (such as GSH) to activate the bleomycin-metal complex, which in turn reacts with oxygen to generate free radicals and peroxides. Our data suggest that either GSH is not required to cycle reducing equivalents to the oxidized bleomycin-metal complex, or the low levels of depleted GSH attained (less than 5% of control) were still sufficient to effect reduction. Further, our data shows that GSH in fact provides a means of protection and detoxification from the cytotoxic effects of bleomycin. Our data suggest that caution should be exercised clinically when one uses drugs that modulate GSH because there may be either enhancement of normal tissue toxicity or decreases in tumor targeted cytotoxicity resulting from bleomycin treatment.

Animals↗
PubMed1984

Insulin removal in man: in vivo evidence for a receptor-mediated process.

To evaluate the in vivo participation of insulin receptors in both hepatic and extrahepatic removal of insulin, compartmental kinetic analysis of insulin behavior was performed in a patient with blocked receptors due to endogenous antiinsulin receptor antibodies. Using the standard three-compartment simulation of insulin behavior, the responses to both a 5-U injection of exogenous insulin and a 4.2-U secretion of endogenous insulin subsequent to tolbutamide injection were examined. In response to both exogenous and endogenous insulin, hepatic removal of insulin was reduced to less than 18% of the insulin exposure (normal, 40-60%). The metabolic clearance of insulin was reduced from the normal level of 520 ml/min to less than 120 ml/min, consistent with a reduction in receptor-mediated removal of insulin from the blood. These studies propose quantitative parameters for insulin receptor function in hepatic and extrahepatic removal of insulin in man.

Adult↗
PubMed1980

A systematic approach to reconstructing microcircuitry by electron microscopy of serial sections.

To observe certain quantitative features of neuronal geometry and microcircuitry, it is necessary to reconstruct neurons from electron micrographs of serial, ultra-thin sections. We describe here an approach to preparing, photographing, and analyzing moderately long series (100-500 sections). A series is prepared using an assembly line approach: one operator cuts while a second mounts ribbons of sections using various mechanical aids. Photographs are taken in the electron microscope at low magnification and high accelerating voltage. Sequential negatives are aligned using an image combiner and copied, using quasi-coherent illumination, onto 35 mm film. The resulting "movie' is mounted on a precision film transport mounted on an X-Y stage controlled by stepping motors. The movie is viewed through a high resolution video system while a video storage device and switching system permit rapid alternation between frames for comparisons. The profiles of a process in successive frames are "microaligned' by small adjustments of the transport's X-Y position. The absolute X-Y biological coordinates for each frame and the correction necessary to bring it into alignment are stored in a Z80 microprocessor as a process vector. When the movie is re-examined with the stepping motors under control of the computer, the microaligned process shows almost no frame-to-frame jitter. The process vector may be used to generate a "branch schematic' of the neuron. The microaligned profiles can also be digitized and displayed as a reconstruction using a PDP 11/34 computer. Uses of the approach are presented with examples from the cat retina and visual cortex.

Animals↗