PubMed Health⌕ Search

Biomedical subjects

M J Pine

Publications and source records attributed to M J Pine.

At least 19 recordsLinked to original sources
PubMed1989

Production of N1-acetyl spermidine by renal cell tumors.

In the RPMI mouse renal cell tumor, N1-acetylspermidine (N1AS) was found to be a constant and major component (18 to 25%) of the polyamine pool. Early i.m. growth induced urinary N1AS excretions up to tenfold normal, equivalent to a daily turnover of the entire tumor polyamine pool. N1AS excretion was correspondingly lower during more limited s.c. tumor growth. In nine other mouse tumors, N1AS pools were low or negligible, and correspondingly urinary N1AS or N8AS increased only in advanced growth, and less significantly. Urinary N1AS was elevated likewise in immature untumored mice. Thus, the enriched N1AS pool of the renal cell tumor was separately distinguishable as a direct source of elevation of urinary N1AS. N1AS was selectively abolished from the renal cell tumor by prolonged BCNU treatment, but was not rapidly depleted by the polyamine inhibitor DFMO. In cell culture, the RPMI renal cell tumor contained unusually high uninduced levels of sperm(id)ine N1-acetyltransferase, a potential source of N1AS. N1AS pools were also significantly elevated in human renal cell tumors.

Animals↗
PubMed1983

Antitumor studies of 2-amino-2-thiazoline and other tumor-modifying agents.

2--amino-2-thiazoline (AT) and 1-thiazolidine-4-carboxylate (TC, thioproline), which have been previously proposed as agents of reverse transformation, have been examined as antitumor agents in several rodent tumor systems. AT administration reduced tumor incidence in sym-dimethylhydrazine treated outbred ICR Swiss female mice and doubled the survival of DBA/2Ha female mice infected with polycythemic Friend leukemia virus. Indomethacin, pentoxyphylline, RA233 and diethyldithiocarbamate (DTC), with potential for altering host or tumor prostaglandin levels, platelet aggregation and host immunity, respectively, ranged from marginally effective to ineffective against Friend virus infection. AT was, however, ineffective against 4 other induced and transplanted mouse tumors and did not notably increase differentiation or decrease transformation in any of several tumor cell systems. No in vitro or in vivo tumor system was found to be more than marginally affected by TC. Thus, AT alone was of significant antitumor activity in inhibiting late stages of viral- or carcinogen induced tumor progression, but could not be demonstrated as an agent of reverse transformation.

Animals↗
PubMed1982

Free amino acid pools of rodent mammary tumors.

Intracellular pools of free amino acids were compared individually in mammary tumors of Wistar Furth and Sprague-Dawley rats and C3H and DBA/2 mice. Of 11 transplantable and 7,12-dimethylbenz[a]anthracene-induced adenocarcinomas of the rat, all nonmetastasizing tumors could be distinguished from metastasizing tumors by the accumulation of high glutamine pools and significant-to-high cystathionine pools. In primary mammary tumors of C3H mice and transplanted mammary tumors of DBA/2 mice, intracellular free arginine was frequently below that of the circulating plasma level and approached that in the arginine-destroying organ, the liver. Arginine pool depletion was also noted in normal mammary tissue, particularly in the actively lactating mouse. Individual rat or mouse mammary tumors also contained high levels of taurine, beta-alanine, and gamma-aminobutyric acid, which, like cystathionine, are distinctive for or are enriched in neural tissue. None of these pool enrichments were characteristic of normal rat or mouse mammary tissue. Free hydroxyproline was low in primary induced rat mammary tumors and higher in transplanted mammary tumors and in normal lactating mammary glands, particularly in the mouse. In contrast, the hydroxyproline residues of collagen, taken as an index of mesenchymal cell contribution, were very low in all tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Improved host defense against L1210 leukemia by deprivation of dietary phenylalanine.

Restriction of phenylalanine to 0.08%, or less, of the diet has been shown to prolong the survival of L1210 leukemia-bearing DBA/2Ha mice or (DBA/2Ha female X BALB/c male) F1 hybrids. A clonal assay was developed for determining the infiltration of L1210 cells without adaption to cell culture. Phenylalanine restriction significantly reduced at the infiltration of IP implanted tumors in tissues of minimal tumor involvement, such as bone marrow and brain. These tumor reductions did not occur with dietary limitations of isoleucine, leucine, cystine-methionine or protein. Tumor infiltration rose to control levels when phenylalanine-limited hosts were immunosuppressed with whole body irradiation or with cyclophosphamide. The L1210-responding BALB/c host when phenylalanine-restricted required a 2- to 3-fold increase in dosage of whole body irradiation in order to succumb to the tumor. In vitro complement-dependent and -independent cytotoxicity of the splenocytes of several host strains immunized to both L1210 cells and sheep erythrocytes were, however, generally reduced by phenylalanine depletion. Phenylalanine depletion is postulated to favor the development of an unidentified immunoproductive and radiation-resistant component of host tumor response.

Animals↗
PubMed1978

Comparative physiological effects of incorporated amino acid analogs in Escherichia coli.

The relative toxicities of several incorporated analogs of phenylalanine, methionine, arginine, and proline were assessed by a variety of criteria in a derivative of Escherichia coli 15 requiring the antagonized amino acids. Toxicity of the analog-substituted cell protein was most consistently indicated by its insolubility at graded temperatures, its increased breakdown, the relative suppression of further cell growth, and lethality. The relative toxicity of poorly utilized analogs could be judged clearly only by the first two criteria. Toxicity generally increased as follows: selenomethionine < 2,5-dihydrophenylalanine and m-fluorophenylalanine < o-fluorophenylalanine and norleucine < ethionine < p-fluorophenylalanine < azetidine-2-carboxylate < canavanine. The overall perturbation of cell protein structure indicated by the toxicity of the methionine and phenylalanine analogs correlated with their alteration of charge and bulk and was greatly modified by minor positional modifications of fluorine. Among the more specific functional impairments, the activity and heat stability of beta-galactosidase were lowered in parallel by substitutions of phenylalanine and methionine analogs, but not in the usual order of toxicity. Flagella were transiently motile with p-fluorophenylalanine, moderately motile with m-fluorophenylalanine, and fully motile with all methionine analogs. Usually the analog incorporations were no more than bacteriostatic in E. coli strains, canavanine killing only the E. coli 15 substrain extensively in minimal media. Selenomethionine supported indefinite growth of procaryotes such as Bacillus subtilis and certain E. coli strains, but only upon supplementation, at least initially, with many nonessential metabolites.

Amino Acids↗
PubMed1975

Incorporation of L-2,5-dihydrophenylalanine into cell proteins of Escherichia coli and sarcoma 180.

l-2,5-Dihydrophenylalanine is extensively incorporated as a phenylalanine analogue into cell proteins. Phenylalanine-requiring Escherichia coli ATCC 9723f and sarcoma 180 grow at normal rates initially with the analogue and maximally replace 65 and 33%, respectively, of phenylalanine in the peptide residues of their cell protein without death. With the analogue alone growth of E. coli becomes non-steady-state and asymptotically inhibited. In mixtures of the analogue and phenylalanine, growth eventually becomes steady state or logarithmic. The logarithmic rate is inversely proportional to the extent of incorporation of this analogue or of p-fluorophenylalanine, and the projected maximal replacement is the same as that obtained asymptotically with the analogue alone. Thus, the toxicities in steady-state and non-steady-state growth are closely related. Moreover, it is proposed that single salient protein defects may determine the extent of growth rate reduction.

Animals↗
PubMed1973

Regulation of intracellular proteolysis in Escherichia coli.

Individual nitrogenous metabolites have been examined as regulating agents for the breakdown of intracellular proteins in Escherichia coli. Generally, NH(4) (+) is the most effective regulator. Its depletion progressively increases the basal proteolytic rate to maximum in most strains when the doubling time is increased to 2 h. In E. coli 9723, the rate is further increased at longer doubling times. Amino acids have individual effects on intracellular proteolysis. The basal rate in amino acid-requiring auxotrophs of E. coli 9723 is stimulated weakly by starvation for histidine, tryptophan, or tyrosine, moderately by four other amino acid depletions, and more strongly by eight others. The degree of stimulation roughly correlates with the frequency of the amino acid in the cell proteins. Amino acid analogues that incorporate extensively into protein generally slightly inhibit intracellular proteolysis, except for selenomethionine, which is slightly stimulatory. Metabolic inhibitors were studied at graded concentrations. Chloramphenicol inhibits the basal level of intracellular proteolysis when protein synthesis is slightly or moderately inhibited, and stimulates proteolysis slightly at higher levels. Graded inhibition of ribonucleic acid synthesis with rifampin progressively stimulates intracellular proteolysis. Uracil depletion is also stimulatory. Inhibition of deoxyribonucleic acid synthesis with mitomycin C or by thymine starvation slightly inhibits intracellular proteolysis. Intracellular proteolysis is postulated to be regulated primarily by active ribosomal function. At 43 to 45 C, intracellular proteolysis becomes maximally induced and unresponsive to normal regulatory control by metabolites. Most regulation is directed towards the breakdown of the more stable cell proteins. Total proteolysis in all cell proteins is no more than doubled by the most effective conditions of starvation.

Amino Acids↗
PubMed1973

Stringent control of intracellular proteolysis in Escherichia coli.

Regulation of intracellular proteolysis has been compared during amino acid deficiencies in seven double auxotrophs of Escherichia coli 9723f with a common phenylalanine requirement. Individual deficiencies were either more effective than, less effective, or equal to phenylalanine deficiency in stimulating intracellular proteolysis. For each amino acid, the same relationship prevailed in inhibiting uracil incorporation into nucleic acids, a reaction series regulated by the rel gene for stringent control. The three amino acids least abundant in the cellular protein were the least effective regulators. These findings are interpreted as supportive evidence for stringent control of intracellular proteolysis by the rel gene.

Amino Acids↗
PubMed1970

Steady-state measurement of the turnover of amino acid in the cellular proteins of growing Escherichia coli: existence of two kinetically distinct reactions.

Turnover of cellular protein has been estimated in Escherichia coli during continuous exponential growth and in the absence of extensive experimental manipulation. Estimation is based upon the cumulative release into carrier pools of free leucine-1-(14)C over a number of time intervals after its pulsed incorporation into protein. Breakdown rates obtained with other labeled amino acids are similar to those obtained with leucine. Two kinetically separate processes have been shown. First, a very rapid turnover of 5% of the amino acid label occurs within 45 sec after its incorporation, most likely indicating maturative cleavages within the proteins after their assembly. A slower heterogeneous rate of true protein turnover follows, falling by 39% in the remaining proteins for each doubling of turnover time. At 36 C, the total breakdown rate of cellular protein is 2.5 and 3.0% per hr over a threefold range of growth rate in glucose and acetate medium, respectively. This relatively constant breakdown rate is maintained during slower growth by more extensive protein replacement, one fifth of the protein synthesized at any time in the acetate medium being replaced after 4.6 doubling times. Intracellular proteolysis thus appears to be a normal and integral reaction of the growing cell. The total rate equals minimal estimates obtained by others for arrested or decelerated growth but is kinetically more heterogeneous. Quantitatively proteolysis is not directly affected by growth arrestment per se as caused by alpha-methylhistidine, chloramphenicol, or uncouplers of oxidative phosphorylation, but qualitatively it can gradually become more homogeneous kinetically as a secondary event of starvation. Under more extreme conditions as with extensive washing, prolonged phosphorylative uncoupling, or acidification of the growth medium, the proteolytic rate can increase severalfold.

Acetates↗
PubMed1969

Taxonomic comparison of the amino termini of microbial cell proteins.

A comparison was made of the distribution of amino terminal end groups in the cellular proteins of a number of microbes. Among the procaryotes, methionine is a highly variable but virtually ubiquitous major protein end group. This is consistent with its possible role as a general amino acid initiator of protein biosynthesis in the procaryotes. Generally, however, alanine is the most abundant of the major end groups, followed in decreasing order by serine, threonine, the acidic amino acids, and occasionally lysine. No other new major end-groups were found. Among 15 representatives of the Enterobacteriaceae, retention of the initiating methionine terminus of the cellular protein varies considerably at a tribal level and is randomized at a familial level. The profiles of the five remaining end groups, however, are strikingly uniform, and are, for example, close to but significantly different from those of the Erwineae. Among the taxonomically more heterogeneous Bacillaceae, end-group profiles vary more and are sometimes unrelated. End-group analysis is thus particularly useful as a molecular criterion of taxonomy in assessing familial homogeneity. Free NH(2) termini in eucaryote cell proteins are fewer, and they have increased acidic amino acid components and no methionine; they are otherwise similar to those of the procaryotes.

Alanine↗