Search PubMed⌕ Search

Biomedical subjects

N Friedman

Publications and source records attributed to N Friedman.

At least 73 records · Page 4Linked to original sources
PubMed1991

Population of the triplet states of bacteriorhodopsin and of related model compounds by intramolecular energy transfer.

In variance with chlorophyll-based photosynthetic pigments, the triplet states of rhodopsins, either visual or photosynthetic, have not been observed experimentally. This is due to the ultrafast crossing from S1 to S0, which effectively competes with intersystem crossing to the triplet (T1) state. In order to populate T1 indirectly, laser photolysis experiments are performed with model protonated Schiff bases of retinal in solution, in which both inter- and intramolecular energy transfer to the polyene chromophore are carried out from an appropriate triplet energy donor. The experiments are then extended to bacteriorhodopsin (bR) by detaching the native retinal chromophore from the protein-binding site and replacing it by an analogous (synthetic) protonated Schiff base polyene, attached in a nonconjugated way to a naphthone triplet donor. Pulsed laser excitation of the latter moiety led, for the first time, to the observation of the triplet state of a rhodopsin. Possible locations and roles of the T1 state in bR and in visual pigments are discussed briefly.

Bacteriorhodopsins↗
PubMed1991

Radiation sensitivity of human B-lineage lymphoid precursor cells.

We studied the radiation sensitivity of eight immunophenotypically distinct B-lineage lymphoid precursor cell (LPC) lines of acute lymphoblastic leukemia (ALL) or fetal liver origin corresponding to discrete developmental stages of human B-cell ontogeny. The radiation sensitivity of B-lineage LPC showed a temporal association with the distinct stages of development. FL112 and FL114 fetal liver pro-B cells (Stage 0 B-lineage LPC) with germline immunoglobulin heavy chain (IgH) genes but rearranged T-cell receptor gamma (T gamma) genes (DO of FL112 = 80.3 cGy, DO of FL114 = 50.2 cGy), REH ALL pre-pre-B cells (Stage I B-lineage LPC) with rearranged IgH and T gamma genes (DO = 66.1 cGy), and NALM-6 ALL pre-pre-B/pre-B cells (Stage II B-lineage LPC) (DO = 50.5 cGy) corresponding to the earliest three stages of human B-lymphocyte development were the most radiation sensitive B-lineage LPC populations. By comparison, KM-3 ALL pre-B (Stage III B-lineage LPC) (DO = 194.7 cGy), HPB-NULL ALL pre-B (Stage IV B-lineage LPC) (DO = 134.6 cGy), and sIgM+ RAJI/NAMALWA early B (Stage Va/b B-lineage LPC) cell lines (DO of RAJI = 144.0 cGy, DO of NAMALWA = 165.5 cGy) corresponding to the later stages of human B-lymphocyte development were much more radiation resistant. These results indicate that the radiation sensitivity of B-lineage LPC decreases during maturation within the B-lineage lymphoid precursor pathway. By comparison, the S-phase index (% of S-phase cells as determined by DNA flow cytometry) or proliferation index (% S + G2M), cellular protein content, intracellular glutathione (GSH) level, glutathione-S-transferase (GST) activity, intracellular pH, or free cytoplasmic calcium concentration did not correlate with the radiation sensitivity of the B-lineage LPC.

B-Lymphocytes↗
PubMed1991

Interleukin-2 lymphokine-activated killer cell therapy of non-Hodgkin's lymphoma and Hodgkin's disease.

We conducted a phase II study utilizing interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells as therapy for non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). IL-2 was given at a fixed dose of 3 x 10(6) U/m2/day administered as a 24-h continuous intravenous infusion with LAK cells. Nineteen extensively treated patients were entered and 15 were evaluable. In general, this regimen was reasonably well tolerated with mild toxicities that were rapidly reversible. Patients who completed therapy did so without dose attenuations. However, discontinuation of therapy was necessary in four patients due to atypical toxicities that were not clearly dose related. Two patients (one NHL and one HD) had partial remissions of brief duration, four had disease stabilization, and seven had progressive disease. While there were not sufficient numbers to evaluate critically any NHL or HD subtype, this regimen does not appear to have significant activity for either disease.

Adult↗
PubMed1991

Interleukin-2 with ex vivo activated killer cells: therapy of advanced non-small-cell lung cancer.

A phase II study was conducted to examine the efficacy of interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells as therapy for advanced non-small-cell lung carcinoma (NSCLC). IL-2 was administered at a fixed dose of 6 x 10(6) U/M2 per day as a 24 h continuous intravenous infusion (CIV) with LAK cells. Eleven patients were entered onto this study and six were evaluable. One patient had a near complete response of 18 months duration. Only two patients were able to complete the regimen without dose reduction. This regimen was poorly tolerated with pulmonary toxicity being the major problem. The partial responder was the only patient to undergo more than one course of therapy. IL-2/LAK therapy may have activity in NSCLC and further studies are warranted in this uniformly fatal disease. However, future studies will have to incorporate less toxic IL-2 regimens.

Adult↗
PubMed1990

Misonidazole hypoxic cytotoxicity and chemosensitization in two cell lines with different intracellular glutathione levels.

Nitroimidazoles such as misonidazole (Miso) or SR-2508 are known to be cytotoxic to hypoxic cells and, with preincubation under hypoxic conditions, to sensitize cells to certain chemotherapy drugs, notably melphalan. In addition, these nitroimidazoles afford hypoxic radiosensitization; however, high intracellular glutathione (GSH) levels have been shown to significantly reduce radiosensitization by some nitroimidazoles. Using two cell lines that have an 8-fold difference in cellular GSH content, we have investigated whether inherent GSH levels influence Miso-induced hypoxic cytotoxicity, hypoxic GSH depletion, or chemosensitization to melphalan. Hypoxic incubation with varying concentrations of Miso resulted in greater cytotoxicity in Chinese hamster V79 cells than in A549 human lung adenocarcinoma cells, which have much higher GSH levels. However, the rate of GSH depletion for three concentrations of Miso was the same in the two cell lines, despite the large difference in inherent GSH levels. While the inherent sensitivity to melphalan was markedly different between the cell lines, hypoxic preincubation with 2 mM Miso with subsequent aerobic exposure to melphalan resulted in similar levels of sensitization. These results indicate that the potentiation of melphalan cytotoxicity by hypoxic Miso preincubation can occur independent of intracellular GSH levels.

Animals↗
PubMed1989

Factors affecting the absorption maxima of acidic forms of bacteriorhodopsin. A study with artificial pigments.

The absorption maximum (568 nm) of light-adapted bacteriorhodopsin bR568 undergoes reversible changes after acidification. At pH 2.9, the absorption shifts to 605 nm (forming bR605) and it blue shifts to 565 nm, after further acidification to pH approximately 0.5 (forming bR565). Molecular models accounting for such acid-induced changes are relevant to the structure and function of bacteriorhodopsin. In the present study we approached the problem by applying artificial bR pigments based on selectively modified synthetic retinals. This may allow direct identification of the specific regions in the retinal binding site where the above changes in the protein-retinal interactions take place. We investigated the spectroscopic effects of acid in a variety of artificial pigments, including cyaninelike retinals, retinals bearing bulky groups at C4, short polyenes, and retinals in which the beta-ionone ring was substituted by aromatic rings. The results provide direct evidence for the hypothesis that the generation of bR605 is due to changes in polyene-opsin interactions in the vicinity of the Schiff base linkage. The second transition (to bR565) was not observed in artificial pigments bearing major changes in the ring structure of the retinal. Two approaches accounting for this observation are presented. One argues that the generation of bR565 is associated with acid-induced changes in retinal-protein interactions in the vicinity of the retinal ring. The second involves changes in polyene-opsin interactions in the vicinity of the Schiff base linkage. For both bRw and bRN5, our results do not discriminate between the direct titration of negative or dipolar protein groups in the binding site and changes in the retinal-protein interactions induced by changes in the protein structure outside of the binding site.

Bacteriorhodopsins↗
PubMed1989

Photolysis intermediates of the artificial visual pigment cis-5,6-dihydro-isorhodopsin.

The photolysis intermediates of an artificial bovine rhodopsin pigment, cis-5,6-dihydro-isorhodopsin (cis-5,6,-diH-ISORHO, lambda max 461 nm), which contains a cis-5,6-dihydro-9-cis-retinal chromophore, are investigated by room temperature, nanosecond laser photolysis, and low temperature irradiation studies. The observations are discussed both in terms of low temperature experiments of Yoshizawa and co-workers on trans-5,6-diH-ISORHO (Yoshizawa, T., Y. Shichida, and S. Matuoka. 1984. Vision Res. 24: 1455-1463), and in relation to the photolysis intermediates of native bovine rhodopsin (RHO). It is suggested that in 5,6-diH-ISORHO, a primary bathorhodopsin intermediate analogous to the bathorhodopsin intermediate (BATHO) of the native pigment, rapidly converts to a blue-shifted intermediate (BSI, lambda max 430 nm) which is not observed after photolysis of native rhodopsin. The analogs from lumirhodopsin (LUMI) to meta-II rhodopsin (META-II) are generated subsequent to BSI, similar to their generation from BATHO in the native pigment. It is proposed that the retinal chromophore in the bathorhodopsin stage of 5,6-diH-ISORHO is relieved of strain induced by the primary cis to trans isomerization by undergoing a geometrical rearrangement of the retinal. Such a rearrangement, which leads to BSI, would not take place so rapidly in the native pigment due to ring-protein interactions. In the native pigment, the strain in BATHO would be relieved only on a longer time scale, via a process with a rate determined by protein relaxation.

Isomerism↗
PubMed1989

Positive and negative regulatory elements in the mouse albumin enhancer.

Most enhancer elements so far described are comprised of multiple DNA binding sites for proteins that act to increase the rate of transcription. In this report we show that the far upstream mouse albumin enhancer element (-10.5 to -8.5 kilobase pairs) is a composite of at least three functional regions: a negative region that suppresses an otherwise positive, liver-specific enhancer element and a third region that by itself is inactive but in conjunction with the remaining elements overrides the effect of the negative region. The protein that binds to the overriding element is C/EBP, a liver-enriched transcription factor, whereas the newly identified protein that is responsible for full liver-specific enhancer activity is found in HeLa cell and spleen extracts as well as in extracts prepared from the liver. This latter protein may therefore be an example of a widely distributed protein that because of cell-specific modification or interaction has a tissue-specific, positive action on transcription.

Animals↗
PubMed1989

The Lec4A CHO glycosylation mutant arises from miscompartmentalization of a Golgi glycosyltransferase.

Two CHO glycosylation mutants that were previously shown to lack N-linked carbohydrates with GlcNAc beta 1,6Man alpha 1,6 branches, and to belong to the same genetic complementation group, are shown here to differ in the activity of N-acetylglucosaminyltransferase V (GlcNAc-TV) (UDP-GlcNA: alpha 1,6mannose beta-N-acetylglucosaminyltransferase V). One mutant, Lec4, has no detectable GlcNAc-TV activity whereas the other, now termed Lec4A, has activity equivalent to that of parental CHO in detergent cell extracts. However, Lec4A GlcNAc-TV can be distinguished from CHO GlcNAc-TV on the basis of its increased sensitivity to heat inactivation and its altered subcellular compartmentalization. Sucrose density gradient fractionation shows that the major portion of GlcNAc-TV from Lec4A cells cofractionates with membranes of the ER instead of Golgi membranes where GlcNAc-TV is localized in parental CHO cells. Other experiments show that Lec4A GlcNAc-TV is not concentrated in lysosomes, or in a post-Golgi compartment, or at the cell surface. The altered localization in Lec4A cells is specific for GlcNAc-TV because two other Lec4A Golgi transferases cofractionate at the density of Golgi membranes. The combined data suggest that both lec4 and lec4A mutations affect the structural gene for GlcNAc-TV, causing either the loss of GlcNAc-TV activity (lec4) or its miscompartmentalization (lec4A). The identification of the Lec4A defect indicates that appropriate screening of different glycosylation-defective mutants should enable the isolation of other mammalian cell trafficking mutants.

Animals↗
PubMed1989

Serum amyloid A: an extremely sensitive marker for intensity of tissue damage in trauma patients and indicator of acute response in various diseases.

Acute response after traumatic events was studied in serial serum samples of 21 patients over a period of 13 days. Among the various biochemical and hematologic parameters, serum amyloid A (SAA) exhibited the most striking changes, with a pattern similar to that of the tissue marker creatine-P kinase (CPK). Maximal SAA level was detected 3-4 days after onset of the event, and reached 216 +/- 41 SEM gm/ml (normal range less than 2 gm/ml), while maximal CPK level was detected on the same day and reached 530 +/- 242 SEM IU/L (normal range 24-195 IU/L). Fibrinogen, leucocytes, platelets, albumin, alkaline phosphatase (AP), and calcium (Ca) each showed its own typical pattern of change. Fever did not develop. Comparison of SAA levels after various acute events suggests that damage to the myocardium is the most powerful stimulus for SAA induction, followed by traumatic events, arthritis, viral infections, and malignant diseases. It seems therefore that although acute response is considered a generalized reaction, it is not completely independent of the localized events which induce it. Among the known parameters, SAA is the most sensitive marker for monitoring the intensity of events.

Acute-Phase Proteins↗
PubMed1989

A dentist oriented fear reduction technique: the iatrosedative process.

This article describes a treatment process that significantly reduces learned dental fear and can be performed by the dentist in 30 to 40 minutes. The findings support the conclusion that the process is effective for calming the fearful dental patient. The iatrosedative process is cost and time effective. It is a procedure the dentist can learn readily, and it can substantially diminish the fear that interferes with treatment.

Adult↗
PubMed1988

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

The classification system of maladaptability presented in a previous paper was reviewed in the present one. Three major sources that significantly influence patient responses to tooth loss and subsequent dentures were discussed. They are parental influences, the symbolic significances of teeth, and current life circumstances. Each of the maladaptive categories is represented by these histories.

Adaptation, Psychological↗
PubMed1988

Glutathione and related enzyme activity in human lung cancer cell lines.

Glutathione levels were measured in 30 human lung cancer lines. Lower levels were detected in cell lines derived from small cell lung cancer specimens compared to non-small cell lines (mean 42 vs. 130 nmol mg-1 protein, P = 0.005). However, no difference were detected between cell lines derived from previously untreated patients, compared to those derived from patients who had received chemotherapy. Non-small cell lines were found to have increased activity of 4 detoxification enzymes compared to small cell lines, although these differences did not reach statistical significance: glutathione transferase activity (69 vs. 36 units, P = 0.137), glutathione reductase (139 vs. 82 units, P = 0.05), gamma-glutamyl transpeptidase (9.39 vs. 3.03 units, P = 0.072) and superoxide dismutase (20 vs. 13.6 units, P = 0.137). As the cell lines exhibit a similar chemosensitivity pattern to that observed in clinical practice, these differences in glutathione and detoxification enzyme levels may prove to be important indicators of intrinsic drug resistance often seen in patients with non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1988

Chinese hamster pleiotropic multidrug-resistant cells are not radioresistant.

The inherent cellular radiosensitivity of a Chinese hamster ovary pleiotropic cell line that is multidrug resistant (CHRC5) was compared to that of its parental cell line (AuxB1). Radiation survival curve parameters n and D0 were 4.5 and 1.1 Gy, respectively, for the CHRC5 line and 5.0 and 1.2 Gy, respectively, for the parental line. Thus, the inherent radiosensitivity of the two lines was similar even though key intracellular free radical scavenging and detoxifying systems employing glutathione, glutathione transferase, and catalase produced enzyme levels that were 2.0-, 1.9-, and 1.9-fold higher, respectively, in the drug-resistant cell line. Glutathione depletion by buthionine sulfoximine resulted in the same extent of aerobic radiosensitization in both lines (approximately 10%). Incorporation of iododeoxyuridine into cellular DNA sensitized both cell lines to radiation. These studies indicate that pleiotropic drug resistance does not necessarily confer radiation resistance.

Animals↗