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Biomedical subjects

O M Rennert

Publications and source records attributed to O M Rennert.

At least 19 recordsLinked to original sources
PubMed1979

Isolation and characterization of a polyamine-peptide conjugate from human amniotic fluid.

Significant amounts of the diamine putrescine and the polyamines spermidine and spermine could be detected in human third-trimester amniotic fluid only after acid hydrolysis. This observation was interpreted to mean that these amines existed only in conjugated form in this biological fluid. Upon fractionation by ultrafiltration 90--10% of the putrescine was associated with the 1000--10 000 dalton fraction. Spermine was identified in this fraction and in a low-molecular weight fraction presumably representing acetylated derivatives. Spermidine was entirely associated with the 10 000--30 000 dalton fraction. The putrescine conjugate was purified to homogeneity by column chromatography on Biogels P10 and P6 followed by ion-exchange chromatography on DEAE-Sephadex A-25. Molecular weight by gel exclusion using peptide standards was estimated to be approx. 4600. The UV absorption spectrum of the putrescine conjugate conformed to that expected for a polypeptide. This putrescine conjugate contained 39 identified amino acids with a combined molecular weight of 4713. Putrescine was detectable by high pressure liquid chromatography only after acid hydrolysis of the conjugate. No other polyamines were detected in these hydrolyzates, nor were any polyamines demonstable in hydrolyzates of control peptides nor in pooled column washes. The identity of the putrescine determined by high pressure liquid chromatography was confirmed by a two-dimensional thin-layer chromatography method. These results establish the in vivo production of a putrescine--polypeptide conjugate in man. Such molecular species may constitute yet another metabolic pathway for polyamines or may reflect another mode of post-translational modification of polypeptide structure and function. The qualitative and quantitative analysis of polyamine conjugate in human aminotic fluid may prove to be useful in the detection of abnormalities in fetal development.

Amino Acids↗
PubMed1979

Polyamine conjugates and total polyamine concentrations in human amniotic fluid.

A study of the quantitative profile of polyamines in amniotic fluid from the 13th through the 40th week of gestation was undertaken. These experimental observations indicate the absence of free putrescine, spermidine and spermine throughout gestation. Quantities of acid-liberated putrescine, spermidine and spermine are highest in late first and late third trimester. Putrescine is associated with peptide or peptides of molecular weight 1000 to 10 000 throughout gestation. Spermidine is found in amniotic fluid covalently conjugated to peptide or peptides with molecular weight 10 000 to 30 000. Spermine appears to exist in amniotic fluid, both in the higher molecular weight fraction (1000 to 10 000) and as acetylated derivatives. The existance of polyamine conjugates is compatible with an in vivo function in the regulation of embryonic growth and development. Abnormalities in polymines conjugated to peptides or their concentration may be useful in the diagnosis of fetal maldevelopment.

Amniotic Fluid↗
PubMed1979

Folate antagonism following teratogenic exposure to diphenylhydantoin.

Previous studies have reported indirect evidence for the mediation of folate antagonism in the induction of malformations by diphenylhydantion. We have demonstrated that a teratogenic regimen of folate-deficiency and antagonism using 9-methyl PGA in the rat produces significantly decreased rates of oxygen consumption in the maldeveloping embryos. The present study reports similar reductions in oxygen uptake by mouse embryos from mothers treated with teratogenic doses of diphenylhydantoin, and documents a significant depression of the actual folate levels in such embryos. The differences are less significant with lower doses of diphenylhydantoin, and do not occur with a nonteratogenic dose.

Abnormalities, Drug-Induced↗
PubMed1979

Mucopolysaccharides in osteochondrodysplasias.

Mucopolysaccharide (MPS) metabolism in cultured skin fibroblasts was studied in one case of each of the following osteochondrodysplasias: chondrodysplasia punctata of the rhizomelic type, thanatophoric dysplasia, campomelic dysplasia, and osteogenesis imperfecta congenita. Accumulation of both sulfated and non-sulfated MPS, as well as secretion of total MPS, was normal in chondrodysplasia punctata of the rhizomelic type and in thanatophoric dysplasia. Accumulation of both sulfated and non-sulfated MPS was normal in campomelic dysplasia. Lastly, accumulation of sulfated MPS was normal in osteogenesis imperfecta congenita.

Cells, Cultured↗
PubMed1979

Serotypes and antibiotic susceptibilities of Pseudomonas aeruginosa isolates from single sputa of cystic fibrosis patients.

A phenotypic characterization of Pseudomonas aeruginosa from single sputum samples of 21 typical cystic fibrosis patients indicated a high frequency of heterogeneity among isolates on the basis of differences in antibiotic resistance, colony morphology, pigmentation, and serotype. Two or more isolates with different but stable susceptibilities to carbenicillin, gentamycin, streptomycin, tetracycline, chloramphenicol, and sulfamethoxazole plus trimethoprim were detected in 38% of the sputa. Differences generally were independent of the mucoid state of the strain. O-antigen group determination with the Difco typing set showed that two or more serologically distinct strains were present in 10/21 sputum specimens. Nonmucoid derivatives of mucoid isolates almost always retained both the antibiotic susceptibilities and serotype of their parent strain. These data suggest that cystic fibrosis patients may be cocolonized/coinfected by different strains of P. aeruginosa more frequently than generally believed. Alternatively, phenotypically distinct strains from a single patient might arise as phenotypic dissociants from a single infecting strain. Because of the frequency and multiplicity of phenotypically distinct P. aeruginosa isolates which we obtained from our cystic fibrosis patients, it is important to select multiple isolates from sputum cultures for antimicrobial susceptibility testing so as to assess adequately the susceptibility of this organism to antibiotic therapy in cystic fibrosis. We recommend that several colonies of each distinguishable colony type of P. aeruginosa be pooled for the antibiogram.

Adolescent↗
PubMed1979

Inducibility of metallothionein biosynthesis in cultured normal and Menkes kinky hair disease fibroblasts: effects of copper and cadmium.

Metallothionein biosynthesis is not induced by extracellular copper in Menkes Kinky hair disease (MKHD) or in normal cultured fibroblasts under the conditions of these experiments. In the presence of copper, MKHD fibroblasts also incorporated less cysteine than did normal fibroblasts. Extracellular cadmium greatly enhanced the uptake of cysteine in both normal and MKHD cultures. By the technique of polyacrylamide gel electrophoresis, it was demonstrated that metallothionein is induced by cadmium in normal and MKHD-cultured fibroblasts.

Brain Diseases, Metabolic↗
PubMed1978

Cell culture studies of Menkes kinky hair disease.

The dose response as well as kinetics of uptake and retention of copper and cadmium of normal and Menkes kinky hair disease (MKHD) cultured fibroblasts are described. In basal culture medium, intracellular copper concentration in MKHD fibroblasts was approximately 3 times that of control cultures. The intracellular copper concentration of MKHD cells was significantly higher than that of normal fibroblasts at medium copper concentrations below 20 microgram/ml. Death of MKHD cells occurred at medium copper concentrations between 15 and 20 microgram/ml with an intracellular copper level 3 times that at basal medium. Normal cells died at medium copper concentration above 30 microgram/ml with an intracellular copper concentration 19 times that at basal medium. These observations suggested the existence of a regulatory mechanism for maintenance and control of intracellular copper in normal fibroblasts which is effective at medium copper concentrations below 30 microgram/ml. This system is defective in MKHD fibroblasts. In basal medium MKHD and normal fibroblasts had similar intracellular cadmium concentrations; however, at higher medium cadmium concentrations MKHD cells had increased intracellular cadmium levels. The uptake of both 64Cu and 109Cd was significantly higher in MKHD cells than in normal cells, indicating that the uptake of 64Cu and 109Cd is not impaired in MKHD cells. A higher retention of 64Cu was observed in MKHD cells at both 37 degrees C and 4 degrees C. No obvious trend, however, was observed in the difference of retention of 109Cd between MKHD and normal cells. An impairment of egress of copper in MKHD cells is implicated by these results.

Brain Diseases, Metabolic↗
PubMed1978

Metal-binding studies of metallothioneins in Menkes kinky hair disease.

Two species of metallothioneins were isolated from both normal and Menkes kinky hair disease (MKHD) patient livers. Atomic absorption determination of metals indicated that the patient liver metallothioneins had lower copper and cadmium content than normals. Isotope exchange studies, carried out by incubating native metallothioneins with copper-64 or cadmium-109 demonstrated a decreased affinity for copper and an increased affinity for cadmium in both MKHD metallothioneins. An hypothesis is proposed in which metallothionein functions as an intracellular copper carrier and is responsible for the transport of copper between the cells and the surrounding. Change in the copper affinity of the metallothioneins was suggested to be the major abnormality in MKHD.

Adult↗
PubMed1978

Polyamine compartmentalization in various human disease states.

Whole blood was separated into preparations of erythrocytes, mononuclear leukocytes, polymorphonuclear leukocytes, platelets and plasma. Each preparation was analyzed for the concentration of the polyamines putrescine, spermidine and spermine. This was done in 17 controls, 14 patients with psoriasis, four patients with hereditary elliptocytosis, two patients with chronic lymphocytic leukemia and one patient each with lung cancer, non-Hodgkin's lymphoma, sickle cell anemia with mild psoriasis, and progeria. In patients with elevated blood polyamine levels, absorption onto erythrocytes was relatively common, and the spermine/spermidine ratio was useful in localizing abnormalities and characterizing the nature of the polyamine alteration. Proliferative states were associated with elevated spermine/spermidine ratios relative to controls while this relationship was reversed in erythropathies such as hereditary elliptocytosis and sickle cell anemia.

Blood Platelets↗
PubMed1978

Familial ichthyosis, dwarfism, mental retardation, and renal disease.

The nonrandom association of congenital ichthyosis with neurologic impairment, ectodermal dysplasia, dwarfism, hypogonadism, and renal disease has prompted the review of numerous syndromes. The difficulties in characterization of syndromes in the absence of pathognomonic signs is discussed in relation to three siblings presented herein. Despite extensive investigation, underlying metabolic defects remain obscure.

Adult↗
PubMed1978

Spermine and spermidine, modulators of the cell surface enzyme adenylate cyclase.

Adenylate cyclase activity was measured in membrane preparations of cultured fibroblasts from controls and patients with cystic fibrosis. Enzyme activity increased as the transition from exponential growth to confluence occurred; sodium fluoride-stimulated activity more markedly displayed this relationship than basal cyclase activity. The in vitro addition of spermine (1 X 10(-6) to 2 X 10(-3) M) to membrane preparations caused inhibition of basal and sodium fluoride-stimulated enzyme activity, with 50% inhibition of basal activity occurring at 10(-6) M spermine. Spermidine (10(-4) M) caused 15--25% inhibition of adenylate cyclase activity. The increase in fibroblast adenylate cyclase activity during the transition from exponential growth was comparable in cells obtained from cystic fibrosis patients and control subjects. Basal and sodium-fluoride stimulated adenylate cyclase activity as well as inhibition of this enzyme activity by spermidine and spermine were undistinguishable between the different cell genotypes. A potential modulation of cellular proliferative activity through polyamine interaction with the adenylate cyclase system is postulated.

Adenylyl Cyclase Inhibitors↗
PubMed1977

Cerebrospinal fluid polyamine monitoring in central nervous system leukemia.

High-pressure chromatographic analysis of cerebrospinal fluid utilizing the o-phthalaldehyde-fluorescent detection system allows the reproducible detection of acid-soluble polyamines in this extracellular fluid compartment. Measurements made by this method in childhood acute lymphocytic leukemia appear to correlate with the remission-relapse status of the patient. The sensitivity of this analytic technique may allow much earlier detection of central nervous system disease. Studies are presently under way in our laboratories to define the usefulness of this technique to monitor successful chemotherapy of leukemia patients.

Adolescent↗