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Biomedical subjects

G W Kalmus

Publications and source records attributed to G W Kalmus.

31 records · Page 2Linked to original sources
PubMed1976

The role of extracellular material in chick neurulation. I. Effects of concanavalin A.

The distribution of extracellular material (ECM) in developing neuroepithelium of stage 8+ chick embryos was investigated using lanthanum nitrate. The temporal changes in the distribution of ECM was correlated with the ongoing morphogenetic movements. The most striking finding was that as the folds were about to meet, thick dense ECM appeared between leading edges. Concanavalin A inhibited neural tube closure by binding to cell surfaces and disrupting the usual distribution of ECM in developing neuroepithelium.

Animals↗
PubMed1976

Effects of cytochalasin B on the morphogenesis of explanted early chick embryos.

Effects of cytochalasin B (CB) on chick embryos explanted at stages 4-5 and cultured for 24 hours were studied. CB (2-4 mug/ml) inhibited blastodermal expansion and neural tube closure in over 90% of the embryos. Somite formation was inhibited only where neural tissue was very degenerate. The development of other structures was usually unaffected. Cellular degeneration occurred in severely affected neuroepithelium, but cells at various phases of mitosis were found throughout its thickness, suggesting that interkinetic nuclear migration had been inhibited. Electron microscopic studies of the flattened neural tube showed that CB disrupted microfilaments and reduced the number of cytoplasmic extensions, but had no apparent effect on microtubules and other organelles. These effects were reversible. Futhermore, dimethyl sulfoxide, at 0.2-0.4% (concentrations present in 2-4 mug/ml CB medium), had no adverse effect, indicating that the observed abnormalities were direct consequences of CB treatment.

Animals↗
PubMed1975

Studies on cell differentiation: inducing capacity of sulfhydryl-containing amino acids on post-nodal pieces of chick blastoderms.

The inducing capacity of sulfhydryl (SH)-containing amino acids (cysteine and glutathione) on post-nodal pieces (PNPs) of stage 4 chick blastoderms was investigated. PNPs were treated for different lengths of time with chick Ringer's solution (control group) or chick Ringer's solution containing cysteine or glutathione, followed by culturing for 2-10 days on Spratt-Haas agar medium or on the chorioallantoic membrane of 8-day chick embryos. Control PNPs rarely showed differentiation, but those treated with the amino acids for six hours or longer developed structures such as neural tissue, notochord, somite mesoderm, and nephric tubules. The pulsatile tissue was only seen in the PNPs cultured for four days or longer. Two-four hours of treatment was too short to provoke induction in a statistically significant number of PNPs. The highest frequency of induction was noted in those pretreated with glutathione (8 mug/ml) for eight hours, followed by culturing for four days. The magnitude of the inducing capacity and toxicity of the amino acids were concentration dependent: a deleterious effect was observed at 14 mug/ml; the highest frequency of induction occurred at 8 mug/ml, but the frequency decreased as the concentration decreased; at 2 mug/ml all PNPs remained viable, but only a few (9-14%) showed differentiation. The inducing capacity of the amino acids was counteracted by equimolar concentrations of rho-chloromercuribenzoic acid or omega-chloroacetophenone. The effects of glutathione (8 mug/ml) differed from those of Hensen's node grafts in that the former caused sublethal cytolysis and inhibited H-3-uridine uptake in competent ectodermal cells during the first 18 hours of cultivation.

Animals↗
PubMed1975

Teratologic effects of LSD in explanted early chick embryos.

Chick embryos were explanted at stage; 4-7 and cultured for 20 h with or without LSD. At any stage 10 mug/ml LSD or higher caused abnormalities in axial structures, particularly somites, in over 50% of the embryos. LSD had no apparent effect on morphogenesis of the heart, but significantly lowered the pulse rate. Cellular degeneration occurred in severely affected structures, but LSD at embryotoxic doses caused alterations in neither cell morphology nor mitotic activity. The effects of LSD were not permanent, i.e., the embryos retained the ability to undergo normal morphogenesis when, after 4-5 h of treatment with 10 mug/ml LSD, they were subcultured on plain nutrient medium.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Ethanol drinking following 6-OHDA lesions of nucleus accumbens and tuberculum olfactorium of the rat.

Previous studies have shown that lesions of the dopaminergic system in the brain produced by an intracerebroventricular injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), evoke significant changes in ethanol drinking. In the present experiments, dopaminergic systems of Sprague-Dawley rats were lesioned by 6-OHDA infused into either the tuberculum olfactorium or nucleus accumbens, two of the structures implicated in drug-related reinforcement. Prior to the lesion and immediately thereafter, tests for ethanol preference were undertaken in which water was offered in a self-selection situation together with ethanol which was increased in concentration from 3-30% over a 10-day interval. Following the circumscribed ablation of dopaminergic neurons within either the N. accumbens or tuberculum olfactorium, preference for ethanol increased significantly with absolute intakes exceeding 4.0 g/kg at the 7% concentration during the first postlesion drinking test. During the second postlesion preference test, the mean consumption of ethanol exceeded 6.0 g/kg at the 11% concentration and 4.0 to 5.0 g/kg at the 20 and 30 percent concentrations offered to the rats. When adjacent areas just dorsal or lateral to these structures were lesioned by 6-OHDA, no significant change in consumption of ethanol occurred. Thus, it is envisaged that one of the functional roles for the dopaminergic neurons of the N. accumbens and tuberculum olfactorium is to regulate the craving for a drug with addictive liability such as ethanol. As a result of an impairment of normal function of dopamine receptors or a perturbation in the release of this catecholaminergic neurotransmitter, ethanol becomes reinforcing upon repeated exposure. Thus, an addictive-like state consequently ensues. Finally, it is envisaged that the control mechanism underlying the function of the dopaminergic neurons in the medial-basal forebrain is functionally disinhibited in individuals that consume ethanol to the point of abuse.

Alcohol Drinking↗
PubMedDate not supplied

Alcohol drinking in rats is attenuated by the mixed 5-HT1 agonist/5-HT2 antagonist FG 5893.

Over the last three decades, the neurotransmitter serotonin (5-HT) has been implicated in the etiological mechanisms underlying the excessive drinking of ethyl alcohol. Recently, the 5-HT2 antagonist amperozide was found to reduce selectively the high intake of alcohol in the cyanamide-induced drinking rat without any adverse side effects. The purpose of the present study was to determine the action on alcohol drinking of the novel second-generation amperozide-like drug, which is a mixed 5-HT1 agonist/5-HT2 antagonist, FG 5893 (2-[4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-3-pyridinecarb oxylic acid methyl ester). To induce preference for alcohol in Sprague-Dawley rats, the enzyme aldehyde dehydrogenase was inhibited by cyanamide administered in the absence of alcohol in a dose of 10 mg/kg twice a day over three days. A standard three-bottle preference test was used in which water and a maximally preferred concentration of alcohol were offered to each animal. Following control tests of alcohol preference for 3 days, either a saline control vehicle or FG 5893 in a dose of 0.5, 1.0, or 2.5 mg/kg was administered subcutaneously at 1600 and 2200 for 3 consecutive days. Whereas control injections of saline were without effect on alcohol consumption, all doses of FG 5893 significantly reduced the 24-h intake of alcohol in terms of both absolute g/kg and proportion of alcohol to total fluid intake. Further, the 1.0 and 2.5 mg/kg doses of FG 5893 continued to suppress alcohol consumption over two 4-day tests immediately following the injection sequence and after a 40-day interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMedDate not supplied

A single dose of ethanol suppresses rat embryo development in vivo.

In humans and animal models, maternal ethanol consumption during pregnancy results in a variety of fetal defects collectively termed the fetal alcohol syndrome (FAS). Limited follow-up studies suggest that FAS children fail to achieve normal physical or mental development despite significant postnatal intervention. Although the complete FAS appears to result only when chronic, excessive alcohol consumption occurs throughout pregnancy, several investigators have suggested that ethanol consumption at intermediate levels may induce components of FAS. The defect most consistently observed in neonates exposed to ethanol is growth retardation. Even those children whose mothers consume limited amounts of ethanol during pregnancy have a significant incidence of fetal growth deficiency. We now report that a single dose of ethanol administered to female Holtzman rats within 8 hr after mating results in a dose-dependent retardation of cell division in the fertilized ova. The growth retardation is sustained up to 42 hr after the dose and the embryos of young mothers are especially sensitive to ethanol. Animals with high blood alcohol levels (greater than 150 mg/100 ml) show a significant increase in abnormal embryo morphology. These data suggest that maternal consumption of a single dose of ethanol near the time sustained up to 42 hr after the dose and the embryos of young mothers are especially sensitive to ethanol. Animals with high blood alcohol levels (greater than 150 mg/100 ml) show a significant increase in abnormal embryo morphology. These data suggest that maternal consumption of a single dose of ethanol near the time of conception retards embryonic growth and may be detrimental to the developing organism. Further, young female rats receiving a high dose of ethanol had significantly lower uterine weights and a lower number of corpora lutea per ovary, suggesting that a single dose of ethanol has a detrimental effect on maternal reproductive ability.

Alcohol Drinking↗
PubMedDate not supplied

Ethanol-induced inhibition of chick brain growth.

Retarded fetal brain growth is associated with a high incidence of mental retardation among the offspring of chronic alcoholic mothers. Research using an embryonic chick model suggests that ethanol exposure suppresses fetal development including suppression of brain growth. Total brain cyclic AMP content and endogenous brain protein kinase specific activity are not altered by ethanol; however, ethanol exposure does significantly stimulate kinase catalytic activity measured in the presence of saturating amounts of exogenous cyclic AMP.

Animals↗
PubMedDate not supplied

The molecular mechanism of fetal alcohol syndrome (FAS). I. Ethanol-induced growth suppression.

Of the birth defects associated with alcohol consumption during pregnancy, in situ growth retardation resulting in neonates that are small for gestational age is the most common observation in both humans and animal models. A variety of alcohol-induced alterations in maternal, placental and/or fetal physiology have been proposed as the basis for this retarded fetal growth. The molecular mechanism(s) of this retardation, however, is obscure; and it remains to be determined whether the growth suppression is the result of the action of ethanol or its metabolites on embryonic, maternal or placental tissue. Using the embryonic chick as a model which circumvents changes in maternal and placental function, we have measured ethanol-induced growth suppression as a function of embryonic age and ethanol dosage. The data suggest that ethanol per se suppresses the rate of cell division in embryonic tissue resulting in fewer cells/embryo for a given time of gestation. The suppression of cell division is proportional to the ethanol dose and appears to be related to ethanol-induced changes in the metabolism of the prostaglandin hormones and resulting changes in the cyclic-AMP levels of the developing embryos.

Alcohol Dehydrogenase↗