Lipoamino acid conjugates of methotrexate with antitumor activity.

The synthesis, characterization, and in vitro antitumor activity against a wild and a transport-resistant CCRF-CEM cell line is described for a series of alpha,gamma-bisamide lipoamino acid and oligomer conjugates of methotrexate. The influence of the lipophilicity of the conjugates on the cytotoxicity and the dihydrofolate reductase inhibition was investigated. All compounds were more active than their fatty acid conjugate analogues.

Long-term survival after locally aggressive anorectal melanoma.

Anorectal melanoma is a rare disease and, unlike cutaneous melanoma, there are few guidelines regarding optimal management. It has a reputation for having a poor prognosis, which has been attributed to a delay in diagnosis and to a lack of effective systemic therapy. It has also been suggested that the biology of this tumor may differ from that of cutaneous melanoma.

Novel liposaccharide conjugates for drug and peptide delivery.

Sugar-lipid conjugates with general structure 1-4 were prepared by coupling amino sugars with N-Boc-protected lipoamino acids and oligomers. Conjugates with general structure 5 were also prepared from glucuronic acid and methyl 2-aminohexadecanoate. The physicochemical properties of the conjugates were modified by varying the nature and number of sugars or the number of lipoamino acids or their alkyl chain length.

Progesterone in Periplaneta americana and Neobellieria bullata adults from the procuticle phase until first progeny production.

A significant amount of progesterone-like immunoreactive material (150 ng/g) was measured by EIA in the procuticle phase of adult of both sexes of Periplaneta americana. This peak markedly decreased to 1-10 ng/g during sclerotization and was unlikely to be of dietary origin. In the case of 0-hr-old P.

Generalized transduction in the potato blackleg pathogen subsp. by bacteriophage M1.

Using enrichment methods, a new bacteriophage (M1) was isolated, which is capable of generalized transduction in subsp. () strain SCRI1043. M1 is probably a virulent phage and contains double-stranded DNA of approximately 43 kb.

Effect of angiotensin-converting enzyme inhibition in HIV-associated nephropathy.

Angiotensin-converting enzyme inhibition (ACEI) delays progression of diabetic and nondiabetic renal disease. This study examined the effect of fosinopril, 10 mg by mouth daily, in HIV-associated nephropathy (HIV-AN). Twenty patients with HIV-AN were studied.

Nitric oxide does not mediate lipopolysaccharide-induced myocardial depression in guinea pigs.

Objective: To determine the role of nitric oxide as a mediator of lipopolysaccharide-induced myocardial depression.

Design: Prospective, controlled study.

Setting: University research laboratory.

Innervation of the adrenal cortex, its physiological relevance, with primary focus on the noradrenergic transmission.

The current knowledge of the catecholaminergic innervation of the mammalian adrenal cortex is summarized, and macro- and microscopic neuromorphology, including the central nervous system connections of the adrenal cortex, is briefly discussed. Morphological and functional data on the catecholaminergic (i.e.

Lipoproteins, lipid droplets, lysosomes, and adrenocortical steroid hormone synthesis: morphological studies.

Recent studies concerning cellular cholesterol homeostasis suggest that there is a relationship between the serum lipoproteins (low density and high density lipoproteins: LDL and HDL), the intracellular storage of cholesterol (lipid droplets), lysosomes, and the steroidogenic activity of adrenocortical cells. This review surveys the current knowledge on cholesterol import from LDL/HDL by adrenocortical cells, its regulation, and the participation of lipid droplets and lysosomes in this process. The possible role of adrenocortical cell microvilli in the uptake of LDL/HDL is discussed.

Viral labelling of synaptically connected neurons.

A method has recently been developed to study the neuroanatomical connections in the brain by trans-synaptic tract-tracing via neurotropic viruses. Neurotrop viruses injected into a peripheral organ or directly into the central nervous system are transported axonally. Viruses are expressed in the infected neurons and they are transferred through synapses to reach other neurons.

Activity and inhibition of 3-beta-hydroxysteroid dehydrogenase/delta-5-4-isomerase in human skin.

Activity and inhibition of 3 beta-hydroxysteroid dehydrogenase/delta 5-4-isomerase, a key example of biosynthesis of androgenic steroids, in human skin were studied. Whole-width dermal tissue specimens excised from various regions of the male and female body were investigated with an in vitro radioenzyme assay method using dehydroepiandrosterone as substrate. The Michaelis-Menten constant of the enzyme was found to be Km = 10nM and the maximal velocity was Vmax = 0.

Viscosity of rat adrenocortical lipids in different functional states: morphological characteristics.

Impaired adrenocortical steroidogenic activity is often concomitant with morphologically and physiologically altered lipids in the cells of the adrenal cortex. The physical state of these lipid droplets and the morphological characteristics of crystal-shaped bodies were studied in different functional states of adrenocortical cells. In the perinatal period when steroidogenesis is suppressed by a negative feedback mechanism, crystal-shaped bodies (i.

Successful treatment of progressive outer retinal necrosis syndrome.

Purpose: Progressive outer retinal necrosis is a destructive retinopathy found in patients with acquired immune deficiency syndrome. Treatment of this disorder has been unsuccessful in reported patient series, with the patients experiencing profound bilateral loss of vision.

Methods: We treated six patients with combination antiviral therapy, usually with intravenous foscarnet and either ganciclovir or acyclovir.

In vitro inhibition of testicular delta 5-3 beta-hydroxysteroid dehydrogenase and prostatic 5 alpha-reductase activities in rats and humans by strogen forte extract.

Clinical findings indicate that Strogen forte (a standardized extract of the plant Sabalis serrulata) can be use successfully in the medical treatment of benign prostatic hyperplasia. The aim of the present study was to investigate the possible inhibitory effects of the Strogen forte extract on rat and human testicular delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and prostatic 5 alpha-reductase (5 alpha-R). Strogen forte proved to be a direct inhibitor of medium effectivity, with similar IC50 values for rat testicular delta 5-3 beta-HSD (400 +/- 23 micrograms/ml) and human testicular delta 5-3 beta-HSD (212 +/- 8.

In vitro binding of 16-methylated C18 and C19 steroid derivatives to the androgen receptor.

The binding of androgens and structurally related analogues to the androgen receptor was studied. The in vitro experiments were carried out with cytosol of castrated rat prostate, using [3H]R1881 (methyltrienolone) as radioligand. The binding parameters measured were Kd = 1.

Ascorbic acid enhances ferritin mRNA translation by an IRP/aconitase switch.

Replenishment of ascorbate in cultured cells, which are almost uniformly vitamin-deficient, increases ferritin mRNA translation in response to iron by 20-fold (Toth, I., Rogers, J. T.

The role of platelet-activating factor in lipopolysaccharide-induced myocardial depression in guinea pigs.

Purpose: To determine if platelet-activating factor (PAF) is a key mediator of lipopolysaccharide (LPS)-induced myocardial depression in guinea pigs.

Methods: Hartley guinea pigs of either sex received intraperitoneal (IP) injections of either vehicle (n = 45) or one of three chemically dissimilar PAF receptor antagonists (n = 38) followed 30 to 60 minutes later by IP injections of either saline (0.8 mL, n = 33) or LPS (2 to 4 mg/kg, n = 50).

Ascorbic acid enhances iron-induced ferritin translation in human leukemia and hepatoma cells.

Ascorbate is an important cofactor in many cellular metabolic reactions and is intimately linked to iron homeostasis. Continuously cultured cells are ascorbate deficient due to the lability of the vitamin in solution and to the fact that daily supplementation of media with ascorbate is unusual. We found that ascorbate repletion alone did not alter ferritin synthesis.

Identification of phosphoproteins in Escherichia coli.

The substrates of ion- and lipid-stimulated protein kinase activity in extracts of Escherichia coli were purified by chromatography. Subsequent N-terminal sequencing suggests that these substrates include the following: a novel 80 kDa protein co-purifying with RNA polymerase but partially homologous to elongation factor G; a protein with an apparent molecular weight of 65 kDa identified as the ribosomal protein S1; and a 32 kDa protein identified as succinyl CoA synthetase, a key enzyme in the tricarboxylic acid cycle. The phosphorylation of these three proteins was markedly stimulated by the addition of manganese, and occurred on threonine, serine or tyrosine residues as indicated by the stability of the phosphoresidues during acid treatment.

Neuropeptides in the adrenal gland: distribution, localization of receptors, and effects on steroid hormone synthesis.

In this review we defined and classified the neuropeptides (NPs) related to the adrenal gland, according to Palkovits (Frontiers Neuroendocrinol 10:1 1988). The concentration (RIA) and distribution (immunohistochemistry) of NPs, as well as the localization of the receptors (radioligand studies) were summarized. Direct effects of NPs on aldosterone and corticosterone synthesis obtained by in vivo, in situ perfusion, and in vitro experimental approaches were reviewed.