Search PubMed⌕ Search

Biomedical subjects

J Friedman

Publications and source records attributed to J Friedman.

At least 217 records · Page 12Linked to original sources
PubMed1982

Aspartate carbamoyltransferase activity, drug concentrations, and pyrimidine nucleotides in tissue from patients treated with N-(phosphonacetyl)-L-aspartate.

Biopsy specimens were obtained from patients treated with N-(phosphonacetyl)-L-aspartate (PALA) in a phase I clinical trial. Activities of aspartate carbamoyltransferase (ACTase), the target enzyme, in ten specimens before treatment varied from 0.4 to 1.7 units/mg. PALA was measured in protein-free extracts of thirteen specimens by inhibition of rat ACTase. At 1.5 to 145 hr after doses of 1 to 6 g/m2, PALA concentrations were 0.9 to 89 micrograms/g; at 4 hr or later the tissue concentrations were similar to those in plasma (five samples). The observed inhibition of ACTase (17-87%) correlated with the PALA concentrations. Pyrimidine nucleotides were decreased (relative to purine nucleotides) in nine to ten specimens, by 16-72%. ACTase partially purified from human spleen had a Km for carbamoyl phosphate of 20.6 microM and the Ki for PALA was 0.011 microM. The results suggest that inhibition of ACTase by PALA affects the concentration of pyrimidine nucleotides in human tumors in a dose-dependent manner.

Antimetabolites, Antineoplastic↗
PubMed1982

Formation and clearance of tubulointerstitial immune complexes in kidney of rats immunized with heterologous antisera to Tamm-Horsfall protein.

Tubulointerstitial immune complex nephritis was produced by passive immunization of rats with antisera to rat Tamm-Horsfall protein (TH), a surface membrane glycoprotein of the cells of the thick ascending limb of Henle's loop. Circulating anti-TH antibodies were deposited in the kidney after an intravenous injection of rabbit antisera to TH. These anti-TH antibodies combined with TH at the base of tubular cells in the thick ascending limb of Henle's loop and formed granular immune complexes in situ in the space between basal cell surface membranes and tubular basement membranes. Immune complexes were also selectively formed in this site during perfusion of isolated kidneys with antisera to TH. Tubular immune complexes containing immunoglobulin, complement, and TH were maximal during the first week after an intravenous injection while high circulating anti-TH antibody titers were present. As the antibody titers subsequently fell to undetectable levels, tubular immune complexes were rapidly cleared and were virtually absent 4 weeks after the injection. During this clearance phase, rabbit IgG and rat TH were detected in the renal interstitium and in renal hilar lymph nodes. The rapid clearance of subepithelial TH immune complexes contrasts with the prolonged persistance of both glomerular subepithelial immune complexes and basement membrane deposits formed after injection of heterologous antisera to other renal components. The process of rapid clearance of tubulointerstitial immune complexes may allow rapid reversibility of immune injury in tubulointerstitial nephritis.

Animals↗
PubMed1982

Expression and novel structure of a collagen gene in Drosophila.

We report the structure and developmental expression of collagen gene sequences in Drosophila melanogaster. Collagen-like genomic clones were isolated by screening a Drosophila genomic library with a chicken pro alpha 2(I) cDNA clone as a hybridization probe. A 1.5-kilobase (kb) DNA sequence from a 9.2-kb DNA clone (pDCg1) is presented. Unlike the highly fragmented genes for vertebrate type I collagen, there is no evidence of a 54-base-pair primordial unit within this gene segment. Instead, the fragment is composed of two large coding sequences. Together they specify a sequence of 469 amino acids. This collagen product is composed almost entirely of the Gly-X-Y repeat characteristic of peptides involved in triple helix formation. Within the polypeptide there are four minor discontinuities in the Gly-X-Y pattern. Similar interruptions have been observed in a mouse basement membrane collagen protein sequence. Therefore, the Drosophila collagen gene may encode a nonfibrous collagen such as a basement membrane or cuticle collagen or a novel collagenous protein. By using the DNA segment of known sequence as a hybridization probe, a developmental sequence of polyadenylylated RNA samples was screened for the presence of homologous sequences. A RNA species 6.4 kb in length was detected as a prominent band only in the first- and second-instar larval stages. This pattern of developmental hybridization correlates with the production of the cuticle and basement membranes, and the large size of the RNA is consistent with its identification as a collagen-encoding RNA.

Animals↗
PubMed1982

DNA sequence analysis of a mouse pro alpha 1 (I) procollagen gene: evidence for a mouse B1 element within the gene.

In a 3.8-kilobase mouse DNA sequence encoding amino acid sequences for the pro alpha 1(I) chain of type I procollagen, 14 coding sequences were identified which specify a sequence 95% homologous to amino acid residues 568 to 963 of the bovine alpha 1(I) chain. All of these coding sequences were flanked by appropriate splice junctions following the GT/AG rule. These observations suggest, but do not prove, that this pro alpha 1(I) gene is transcriptionally active. Of the 14 coding sequences, 7 were 54 base pairs in length, whereas the remainder were higher multiples of 54 base pairs. Nonrandom utilization of codons pertained throughout all of the coding sequences showing a preference (56%) for U in the wobble position. Two of the intervening sequences encoded imperfect vestiges of coding sequences which exhibited a codon preference different from that of the pro alpha 1(I) gene proper and were not flanked by splice junctions. One intervening sequence encoded a member of the mouse B1 family of middle repetitive sequences. It was flanked by 8-base-pair direct repeats and had a truncated A-rich region, suggesting that it may be a mobile element. Within this element were sequences which could function as a RNA polymerase III split promoter.

Animals↗
PubMed1981

Mutagen-induced resistance to mycophenolic acid in hamster cells can be associated with increased inosine 5'-phosphate dehydrogenase activity.

Cell variants resistant to the cytotoxic effect of mycophenolic acid, an inhibitor of IMP dehydrogenase (IMP:NAD+ oxidoreductase, EC 1.2.1.14), were selected by a one-step procedure from Chinese hamster V79 cells. The frequency of these variants was increased in a dose-dependent manner after treatment with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine and after an expression time of 8 days. The degree of resistance in five of the six isolated cell variants was associated with a comparable increase in the specific activity of IMP dehydrogenase, which was 3- to 6-fold higher than that of the parent V79 cells. The IMP dehydrogenase activity from both the variants and the V79 cells had a similar affinity for the substrate IMP with a Km of about 20 microM and a similar response to mycophenolic acid with a Ki of 12-16 nM. It is suggested that cell variants with an altered regulation of IMP dehydrogenase activity may be helpful in studying the control of nucleic acid biosynthesis, cell growth, and carcinogenesis. Mycophenolic acid resistance also may be useful as a marker in short-term assays for the identification of potential chemical carcinogens.

Animals↗
PubMed1981

Effects of monensin on amylase release from mouse parotid acini.

Isolated mouse parotid acinar cells (acini) were prepared by enzyme digestion, divalent cation depletion, and mechanical shearing. Acini were found to be morphologically intact, i.e., 95% viable as judged by trypan blue exclusion. Amylase release by the cholinergic agonist carbachol, by the beta-adrenergic agonist isoproterenol, and by monensin was similar to responses obtained in mouse parotid fragments. Monensin-stimulated amylase release was associated with enhanced 22Na+ uptake and 45Ca2+ efflux; monensin did not affect 45Ca2+ uptake. In the absence of extracellular Na+, the response to monensin (50 microM) was reduced from 162 +/- 33.5 to 12.4 +/- 0.5%; monensin also failed to stimulate 45Ca2+ efflux. Similar results were obtained with isoproterenol (10(-6) M). The results suggest that Na+ ions may play a role in amylase release possibly by releasing Ca2+ from internal stores.

Amylases↗
PubMed1981

Assets of the elderly as they retire.

This study, using data from the Retirement History Study, indicates that as older Americans enter their retirement years, their property wealth is generally very limited and can seldom be expected to be much help in maintaining their preretirement standard of living. Although most older Americans own some form of assets, the value of these assets is generally quite small. Equity in the home is usually the most important form of asset for the elderly; liquid or income-producing assets are generally very limited in amount. Only a small proportion of respondents have substantial asset wealth. Married men are much more likely to own homes than nonmarried men and women, and are also more likely to own liquid assets of any magnitude.

Age Factors↗
PubMed1981

Epinephrine desensitization of adenylate cyclase from cyc- and S49 cultured lymphoma cells.

The characteristics of the specific beta-adrenergic desensitization of adenylate cyclase from the adenylate cyclase deficient lymphoma cell line (cyc-) and the wild type S49 (WT) are presented in detail in this report. We have previously shown that the cyc- adenylate cyclase desensitized with 1-3 hr pretreatment of the cells with the beta-adrenergic agonist epinephrine. Adenylate cyclase of cyc- was measured after reconstitution with cholate extracts of the coupling proteins (G/F) from WT. We have now demonstrated that: (i) the initial epinephrine-induced desensitization of adenylate cyclase from either cyc- or WT was similar and occurred rapidly, with a half-life of approximately 2 min, although WT desensitized to a greater extent with prolonged hormone treatment (18 hr pretreatment of cyc- or WT with 0.1 mM terbutaline resulted in a 92% desensitization of the WT adenylate cyclase and only a 48% desensitization of cyc-); (ii) the 60 min epinephrine desensitization of cyc- was reversed after addition of propranolol and continued (40-60 min) incubation, while that of WT was only partially reversed; (iii) similar concentrations of epinephrine (0.2-0.4 muM) were required for half-maximal desensitization of both cell lines; and (iv) the Kact for epinephrine stimulation of reconstituted adenylate cyclase from cyc- or WT was increased after a 1 hr desensitization with 10 muM epinephrine. Kact was approximately 5-fold less than the half-maximal concentration required for desensitization. The data support the conclusion that the mechanisms of the rapid, reversible specific beta-adrenergic desensitization of adenylate cyclase in cyc- and WT cells are similar and occur independently of the G/F proteins of the adenylate cyclase complex, whereas the slower, apparently irreversible phase of desensitization occurs only in WT.

Adenylyl Cyclases↗
PubMed1980

Postreplication repair and the susceptibility of Chinese hamster cells to cytotoxic and mutagenic effects of alkylating agents.

A cell variant (VR-43) resistant to the cytotoxic effect of N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N'-nitro-N-nitrosourea was isolated from Chinese hamster V79 cells for use in studies of the relationship among cell survival, mutagenesis, and DNA repair by alkylating agents. Resistance to ouabain or 6-thioguanine was used as the genetic marker. After treatment with N-methyl-N'-nitro-N-nitrosoguanidine, the VR-43 cells exhibited mutation frequencies that were lower, on a dose basis, than those of the wild-type V79 cells. However, when analyzed at equicytotoxic doses, the VR-43 cells were more mutable than the V79 cells. No difference in cell survival or mutagenicity could be observed after treatment with other mutagens such as N-ethyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, or x-rays. Postreplication repair was analyzed by determination of the molecular weight of the newly synthesized DNA by alkaline sucrose gradients. After treatment with N-methyl-N'-nitro-N-nitrosoguanidine, the VR-43 cells exhibited an enhanced postreplication repair relative to the V79 cells. No such enhancement was found after N-ethyl-N'-nitro-N-nitrosoguanidine or ethyl methanesulfonate treatment. Based on these results we propose that, after treatment of these and presumably other mammalian cells with some methylating mutagens, postreplication repair can cope with DNA lesions responsible for cytotoxicity and, to a lesser degree, with lesions responsible for mutagenicity.

Alkylating Agents↗
PubMed1980

Tobacco smoking and cortical evoked potentials: an opposite effect on auditory and visual systems.

1. Auditory and visual evoked potentials produced by five intensities of tones and light flashes were recorded in twelve young men who were habitual smokers. 2. The subjects attended the laboratory on four occasions. Two recordings were made on each of the last three of these visits. They were made (i) before and after smoking, (ii) without smoking, (iii) before and after smoking after 12 h abstinence from smoking. 3. Smoking was associated with increases in the amplitudes of the components V-VI, VI-VII in the visual system and a decrease in the amplitude of N2P2 in the auditory system. Abstinence from smoking produced effects in the opposite direction. 4. These findings are consistent with the possibility that smoking has different and perhaps opposite effects on the visual and auditory system. 5. The findings may be helpful in re-evaluating some of the apparently conflicting reports on the effects of smoking on perceptual processes.

Adolescent↗
PubMed1980

Attention in hysteria: a study of Janet's hypothesis by means of habituation and arousal measures.

Toward the end of the 19th century, Janet suggested that the fundamental disorder in hysteria was one of attention. The authors examined this idea in a study of habituation. Patients with a history of prolonged conversion symptons (N = 11) showed a severe impairment in habituation when compared with patients with anxiety neuroses (N = 10). This finding cannot be explained in terms of arousal and suggests that selective inattention is deficient in hysterical individuals.

Adult↗
PubMed1980

Stimulus intensity control in depression: a study of the comparative effect of doxepin and amitriptyline on cortical evoked potentials.

The perceived intensity of a stimulus may be magnified during depression. Stimulus intensity control can be studied by means of cortical evoked potentials. In a study of 33 depressives, cortical evoked potentials were greater during depression than on recovery. The effect of doxepin on the amplitudes of evoked potentials of depressives was compared with that of amitriptyline. Doxepin reduced amplitudes. Amitriptyline had a similar, but non-significant effect.

Adolescent↗