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Biomedical subjects

M Marx

Publications and source records attributed to M Marx.

At least 145 records · Page 8Linked to original sources

Rous sarcoma virus mutant dlPA105 induces different transformed phenotypes in quail embryonic fibroblasts and neuroretina cells.

dlPA105 is a spontaneous variant of Rous sarcoma virus, subgroup E, which carries a deletion in the N-terminal portion of the v-src gene coding sequence. This virus was isolated on the basis of its ability to induce proliferation of quiescent quail neuroretina cells. The altered v-src gene encodes a phosphoprotein of 45,000 daltons which possesses tyrosine kinase activity. DNA sequencing of the mutant v-src gene has shown that deletion extends from amino acid 33 to 126 of wild-type p60v-src. We investigated the tumorigenic and transforming properties of this mutant virus. dlPA105 induced fibrosarcomas in quails with an incidence identical to that induced by wild-type virus. Quail neuroretina cells infected with the mutant virus were morphologically transformed and formed colonies in soft agar. In contrast, dlPA105 induced only limited morphological alterations in quail fibroblasts and was defective in promoting anchorage-independent growth of these cells. Synthesis and tyrosine kinase activity of the mutant p45v-src were similar in both cell types. These data indicate that the portion of the v-src protein deleted in p45v-src is dispensable for the mitogenic and tumorigenic properties of wild-type p60v-src, whereas it is required for in vitro transformation of fibroblasts. The ability of dlPA105 to induce different transformation phenotypes in quail fibroblasts and quail neuroretina cells is a property unique to this Rous sarcoma virus mutant and provides evidence for the existence of cell-type-specific response to v-src proteins.

Animals↗

Compromised T-cell regulatory functions during anuran metamorphosis: the role of corticosteroids.

Glucocorticoid receptor concentrations, which are undetectable before metamorphosis, increase to a maximum during the metamorphic period and decline to toadlet levels thereafter. The generation of a high concentration of receptors, imparting enhanced glucocorticoid sensitivity particularly to the lymphoid tissues of metamorphic larvae suggests the possibility that increasing endogenous levels could be responsible for the compromised T-cell functions which have been described for these stages of development (Ruben et al, 1985a).

Adrenal Cortex Hormones↗

Treatment of hamster pancreatic cancer with alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis.

Polyamines are essential for cell division and growth. Inhibition of polyamine biosynthesis by alpha-difluoromethylornithine (DFMO) on the growth of hamster H2T pancreatic cancer was investigated both in vitro and in vivo. Cell-doubling time (TD) and survival fraction were determined after a single treatment with DFMO (5 mM). We examined the ability of putrescine to reverse the growth-inhibitory effect of DFMO. The TD for cells treated with DFMO in vitro was 49.6 +/- 5.7 versus 25.4 +/- 2.6 hours for control. The addition of putrescine to DFMO-treated H2T cells showed a reversal of the growth-inhibitory effect of DFMO. Cytotoxicity in vitro increased with prolonged treatment; the survival fraction after 24 hours of treatment was 32%; after 48 hours, 19%; after 72 hours, 13%; and after 92 hours, 8%. We performed two separate animal experiments. In experiment I, H2T cells were injected into the cheek pouch of male Syrian golden hamsters; controls did not receive DFMO. Continuous treatment with 3% DFMO in the drinking water was begun 7 days before, on the day of, or 7 days after tumor cell injection. In experiment II, 4 groups were treated identically to those in experiment I. An additional group of 10 hamsters received 3% DFMO and no tumor, and another additional group of 10 hamsters were housed individually with 3% DFMO begun 7 days after tumor cell injection. Tumor size, body weight, water, and food intake were measured. DFMO treatment in vivo significantly inhibited tumor size and inhibited growth of pancreatic cancer by as much as 50% of control. Our results demonstrate a significant antiproliferative effect of DFMO on the growth of pancreatic adenocarcinoma both in vitro and in vivo.

Adenocarcinoma↗

Phosphorylation of microsome-bound cytochrome P-450 LM2.

The phosphorylation of a microsomal protein of rabbit liver by catalytic subunit of cyclic AMP-dependent protein kinase was shown, and the protein was identified as cytochrome P-450 LM2 on basis of comparative peptide-mapping. Acid hydrolysis of microsome-bound phosphorylated cytochrome P-450 revealed that phosphorylation occurred exclusively on serine residues. This serine residue was identified as the same residue phosphorylated in purified, soluble P-450, that is, serine in position 128.

Animals↗

Temporal frequency-dependent VEP changes in Parkinson's disease.

We recorded steady-state (4.19 and 8.41 Hz) VEPs in 17 Parkinson's Disease (PD) patients and 18 control observers using on-off temporal modulation of a 2.3 c/deg sinusoidal grating. With 4.19 Hz, 20 out of 33 PD patient eyes had abnormal VEPs. However, only 8 of 33 eyes were abnormal with 8.41 Hz. "Routine" (counterphase) transient VEPs revealed delayed VEPs for only 7 out of 24 eyes of the patients. These findings suggest an "input" temporal frequency-dependent abnormality in the foveal pathway.

Adult↗

Nuclear magnetic resonance spectroscopy of rat ventricles following supravalvar aortic banding. A model of left ventricular hypertrophy.

Left ventricular hypertrophy produced by supravalvar aortic banding in infant rats was studied by proton magnetic resonance spectroscopy. Weight gain at 11 weeks of age in the 11 male Sprague-Dawley rats with aortic bands placed at three weeks was similar to that of the 14 controls. The left ventricle of banded rats hypertrophied, increasing the ratio of left ventricle plus septum to body weight (LV + S/BW) by more than 50% (P less than .00001). Right ventricular weight (RV/BW) increased slightly (P less than .03). T1 and T2 relaxation times of LV + S, RV, and thigh muscle (Th) from the banded and control rats were compared. The T2 value distinguished hypertrophied from control LV + S (P less than .003), but not between RV or Th from the two groups. For banded rats only, the T2 value distinguished each muscle type: LV + S from RV, LV + S from Th, and RV from Th (P less than .00001 for each). For control rats, cardiac muscle was distinguished from Th (P less than .00001), but LV + S and RV were similar. The T1 value did not distinguish either the banded from the control group or any of the muscle types. Percent water content was similar for all tissues. Any correlation between water content and T1 or T2 was inconsistent or weak.

Animals↗

Coronary thrombolytic therapy: state of the art.

Ischemic heart disease remains a significant cause of morbidity and mortality in the United States. Thrombolytic therapy has given physicians the capability of limiting the amount of myocardial damage that occurs when there is an acute coronary artery thrombosis and resulting myocardial infarction. This review summarizes current concepts about action mechanisms of the major thrombolytic agents, the technique and clinical results of intracoronary thrombolytic therapy, intravenous vs intracoronary administration, postthrombolytic management of underlying coronary artery disease, new agents being developed, and directions for future investigations.

Coronary Circulation↗

Isolation of a line of immortal chicken embryo fibroblasts after transfection with the nuclei of Rous sarcoma virus-transformed Chinese hamster cells.

Secondary cultures of chicken embryo fibroblasts were transfected with purified nuclei from lysed cells of a clonal line of temperature-sensitive Rous sarcoma virus (tsRSV)-transformed Chinese hamster fibroblasts. After propagation for 3 months an established cell line designated ChR32 was obtained in one chicken cell culture. The cells of this line have been propagated so far for 18 months, whereas normal chicken embryo fibroblasts died after 2 months. The established cells were heteroploid with a diploid modal number of macrochromosomes and two Z chromosomes. No Chinese hamster chromosomes could be identified. Southern blot analysis of DNA from the uncloned ChR32 cells and the clones provided evidence that these established cells were, in fact, clonal in origin and contained full-length RSV proviruses and no defective proviruses. Furthermore, they contained, at the 3' end proviral-cellular junction, Bg/II, HpaI, KpnI, SacI, and XbaI fragments of the same size as the Chinese hamster donor cells, suggesting that the cellular sequence adjacent to the provirus is of Chinese hamster origin. The cells after establishment were able to grow continuously at 37 degrees or 41 degrees C and produce a large amount of ts sarcoma virus particles. A corollary finding was that these virus particles were non-leaky for the transforming function at the non-permissive temperature.

Animals↗

Synthesis and antidepressant profiles of phenyl-substituted 2-amino- and 2-[(alkoxycarbonyl)amino]-1,4,5,6-tetrahydropyrimidines.

A series of 4(6)- and 5-phenyl-substituted 2-amino- and 2-[(alkoxycarbonyl)amino]-1,4,5,6-tetrahydropyrimidines were prepared and evaluated for central nervous system (CNS) effects in animal models. Several 5-phenyl-substituted compounds possessed potent antidepressant activity and all compounds in this series were devoid of significant activity in any of the other CNS (anticonvulsant, muscle relaxant, and depressant) assays. The most active compound in the in vivo screen for antidepressant activity (reversal of reserpine-induced hypothermia), 2-[(methoxycarbonyl)amino]-5-phenyl-1,4,5,6-tetrahydropyrimidine was considerably more potent than tricyclic antidepressant (TCA) standards. The 2-amino parent compound on the other hand was greater than 100-fold as effective as TCA's in in vitro inhibition of norepinephrine and dopamine uptake.

Amines↗

Dissection complicating angioplasty.

Extensive arterial dissection producing significant arterial obstruction or occlusion after technically uncomplicated percutaneous transluminal angioplasty in three patients is described. Despite the initially ominous arteriographic appearance, short-term (4-8 months) follow-up demonstrated complete resolution without surgical intervention. A trial of conservative management is recommended for this complication.

Adult↗

The subplacental complex: further sonographic observations.

The subplacental complex, which represents vascular channels at the placental-myometrial junction, is a structure that is routinely seen sonographically in patients with posteriorly placed placentas, but not in those with anteriorly placed placentas. This study shows that the subplacental complex is a constant anatomic feature of the placenta regardless of whether it develops on the anterior or posterior uterine wall, and can be visualized in most patients if the subplacental complex is in the focal plane of the transducer. This has important implications in patients with anterior placentas that are being evaluated for abruption or in patients in whom fetal parts lie just beneath the anterior myometrial wall.

Female↗

Synthesis and central nervous system properties of 2-[(alkoxycarbonyl)amino]-4(5)-phenyl-2-imidazolines.

A series of 2-[( alkoxycarbonyl )amino]-4(5)-phenyl-2-imidazolines was prepared and evaluated for central nervous system (CNS) effects (antidepressant, anticonvulsant, muscle relaxant, and depressant) in animal models. Some separation of those CNS activities was achieved through substitutions on the phenyl and imidazoline moieties. Halo-substituted phenyl compounds were among the most potent antidepressants in this series, while imidazole N-alkylation produced compounds with increased depressant effects (loss of righting reflex, mouse behavior). Comparison of in vitro and in vivo data for pairs of 2-[(methoxycarbonyl)amino]-4(5)-phenyl-2-imidazolines and their parent, 2-amino-4(5)-phenyl-2-imidazolines, suggests that the title compounds were prodrugs for the 2-amino-4(5)-phenyl-2-imidazolines in inhibition of norepinephrine reuptake.

Animals↗