Showing papers by "University of Colorado Denver published in 1973"

Isolation and characterization of lamellar bodies and tubular myelin from rat lung homogenates

Abstract: Three surface-active fractions which differ in their morphology have been isolated from rat lung homogenates by ultracentrifugation in a discontinuous sucrose density gradient. In order of increasing density, the fractions consisted, as shown by electron microscopy, primarily of common myelin figures, lamellar bodies, and tubular myelin figures. The lipid of all three fractions contained approximately 94% polar lipids and 2% cholesterol. In the case of the common myelin figures and the lamellar bodies, the polar lipids consisted of 73% phosphatidylcholines, 9% phosphatidylserines and inositols, and 8% phosphatidylethanolamines. In the case of the tubular myelin figures, the respective percentages were 58, 19, and 5. Over 90% of the fatty acids of the lecithins of all three fractions were saturated. Electrophoresis of the proteins of the fractions in sodium dodecyl sulfate or Triton X-100 revealed that the lamellar bodies and the tubular myelin figures differed in the mobilities of their proteins. The common myelin figures, however, contained proteins from both of the other fractions. These data indicate that, whereas the lipids of the extracellular, alveolar surfactant(s) originate in the lamellar bodies, the proteins arise from another source. It is further postulated that the tubular myelin figures represent a liquid crystalline state of the alveolar surface-active lipoproteins.

Cyclic adenosine 3',5'-monophosphate in Escherichia coli.

Abstract: The concentration of cyclic adenosine 3′,5′-monophosphate (c-AMP) in Escherichia coli growing on different sources of carbon was studied. Cultures utilizing a source of carbon that supported growth relatively poorly had consistently higher concentrations of c-AMP than did cultures utilizing sugars that supported rapid growth. This relationship was also observed in strains defective in c-AMP phosphodiesterase and simultaneously resistant to catabolite repression; in such strains the c-AMP concentration was slightly higher for several sources of carbon tested. Cultures continued to synthesize c-AMP and secreted it into the medium, under conditions that brought about an inhibition of the intracellular accumulation of the cyclic nucleotide. Transient repression of the synthesis of β-galactosidase was not associated with an abrupt decrease in the cellular concentration of c-AMP.

Effect of nerve degeneration by 6-hydroxydopamine on catecholamine-stimulated adenosine 3',5'-monophosphate formation in rat cerebral cortex.

Abstract: Intraventricular injection of 6-hydroxydopamine leads to two types of alterations in the effect of norepinephrine on the cyclic 39,59-AMP content of slices of rat cerebral cortex: an early-developing, presynaptic effect and a late-developing, postsynaptic effect. The early effect is attributed to the destruction of adrenergic nerve terminals by 6-hydroxydopamine and the resultant loss of presynaptic catecholamine uptake sites. This conclusion is based on three primary observations: (a) the potentiation of the effect of a threshold concentration of norepinephrine (1 µM) by 6-hydroxydopamine followed approximately the same time course as the loss of ability of the slices to accumulate [ 3 H]norepinephrine; (b) cocaine, which inhibits the presynaptic accumulation of [ 3 H]norepinephrine, potentiated the effects of low concentrations of norepinephrine in slices from control rats but did not alter the effect of norepinephrine in slices from 6-hydroxydopamine-treated animals; (c) the EC 50 for norepinephrine was reduced from 5.2 to 1.7 µM by treatment with 6-hydroxydopamine, but the EC 50 for isoproterenol (which is not accumulated presynaptically) was not altered. Also, cocaine did not potentiate the increase in cyclic AMP content induced by isoproterenol in slices from control animals. The increase in the effect (of high concentrations (30 µM) of norepinephrine did not occur until 96 hr after treatment of the rats with 6-hydroxydopamine. This late-developing increase in responsiveness would appear to be a postsynaptic phenomenon, since it occurs during a time span (72-96 hr) when there is no further change in inhibition of the uptake of [ 3 H]norepinephrine. Furthermore, there is an increase in responsiveness to isoproterenol as well as to norepinephrine. Adenosine also causes an increase in the cyclic AMP content of rat cortext slices, but its effects are not altered by prior treatment with 6-hydroxydopamine.

Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome): I. Sulfatase B Deficiency in Tissues

Abstract: Sulfatase B activity was deficient in tissues from patients with type VI mucopolysaccharidosis (Maroteaux-Lamy syndrome; MPS VI). Liver, kidney, spleen, brain, and cultured fibroblasts all showed deficient activity. The sulfatase B deficiency was most evident in assays of pellet fractions. Sulfatase B activity was not reduced in the other mucopolysaccharidoses tested (types I, II, and III). The activities of control lysosomal enzymes (sulfatase A and acid phosphatase) were not reduced in MPS VI tissues. The evidence suggests that a sulfatase B deficiency may underlie the biochemical abnormalities responsible for the MaroteauxLamy syndrome. The findings also lend credence to the view that sulfatase B normally plays a catabolic role as an O-sulfatase in the pathways of sulfated mucopolysaccharide metabolism. The possibility that oligosaccharide chondroitin sulfate B (dermatan sulfate) is a substrate for sulfatase B remains to be critically tested.

Contraceptive steroids: modifications of carbohydrate and lipid metabolism.

Abstract: Although chronic ingestion of contraceptive steroids may produce a variety of metabolic changes, their effect on carbohydrate and lipid metabolism appears to be related to the age and predisposition to metabolic disease of the recipient and to the amounts and relative proportions of estrogen, nortestosterone, and progesterone derivatives in the birth control preparations employed. In healthy intact young women, the separate administration of either synthetic estrogens or progesterone derivatives or nortestosterone derivatives does not consistently alter glucose or insulin metabolism as assessed by serum glucose or insulin concentrations after overnight fasting or following glucose administration. However, the concurrent administration of mestranol or ethinyl estradiol with a nortestosterone derivative produces deterioration of glucose tolerance, which is not observed during concurrent synthetic estrogenprogesterone derivative administration. The changes in glucose tolerance produced by birth control pills are superimposed on the deterioration of glucose tolerance observed with aging. Also, women with borderline pancreatic insulin reserve appear more likely to develop abnormal glucose tolerance than normal women when challenged with contraceptive steroids, although deterioration of glucose homeostasis does not seem to occur frequently in insulin-requiring diabetics using birth control pills. Concurrent mestranol-nortestosterone derivative administration generally enhances the peripheral circulating insulin response to a glucose challenge in normal women and in rhesus monkeys, whereas the individual contraceptive steroids and concurrent synthetic estrogen-progesterone derivative administration generally produce little measurable effect on circulating insulin concentrations. However, the rhesus monkey is not an ideal model for studying the metabolic effects of contraceptive steroids because its glucose tolerance improves with concurrent mestranol-norethindrone administration. No other suitable animal model has been developed for studying the effect of contraceptive steroids on carbohydrate metabolism. Estrogen administration leads to increased fasting serum triglyceride concentrations. Nortestosterone derivatives (but not 17 α-acetoxyprogesterone derivatives) counteract the hypertriglyceridemic effect of estrogens. Both of these effects appear to be dose-related. Contraceptive steroid-inducd hypertriglyceridemia primarily appears to be due to increased hepatic production of triglycerides, although plasma clearance of the triglycerides also seems to be reduced by the estrogen component of contraceptive steroids. Changes in serum cholesterol concentrations produced by birth control pills are small and are related to the age of the patient. In women over 40, total serum cholesterol concentrations decrease during birth control pill use; in women under 40, they increase . When increases in total serum cholesterol concentrations occur, they appear to be related to the amount of nortestosterone or progesterone derivative ingested. The possible relationship of these complex contraceptive steroid-induced changes in carbohydrate and lipid metabolism to the long-term development of cardiovascular diseases is discussed, although the mechanisms involved remain obscure.

Effect of estradiol-17, β on the magnitude and distribution of uterine blood flow in nonpregnant, Oophorectomized Ewes

Abstract: Effect of Estradiol-17, β on the Magnitude and Distribution of Uterine Blood Flow in Nonpregnant, Oophorectomized Ewes

A practical approach to the protection of the abused child and rehabilitation of the abusing parent

Abstract: Many judges and social workers feel that anyone can turn on to mothering. The fact is that some parents frankly do not like their children. They hate them. We don9t find it socially acceptable to let them say so. It is tragic that we don9t. We have faced the problem of parents not getting along and we call that divorce. We must acknowledge as a socially acceptable situation that a parent can admit she cannot mother her child for one reason or another. Allowing a mother or father to say in a socially acceptable way that try as they may, they cannot tolerate this child, will help us on the way to giving protection to all children. I would like to now propose the thought that the quality of mothering is a continuum of from none of it to a lot of it. By mothering, I mean not only the female term but a quality of caring for a defenseless young child, giving without limit if you please, to a tiny child, which fathers have in great abundance as well. This quality saves many lives and can be had by maiden aunts and spinsters and people who have never had a baby. For practical purposes we have to face the fact that very few of us, fathers or mothers, have it in us to be "that kind of a mother" 24 hours a day, seven days a week, all year long. If we have money we can arrange to supplement mothering for pay.

Assessment of significance of proportions of intraductal and infiltrating tumor growth in ductal carcinoma of the breast

Abstract: A series of 267 mammary carcinomas of intraductal or infiltrating duct type treated by mastectomy was divided by histologic examination into 6 groups: pure intraductal carcinoma (14 cases); intraductal carcinoma with less than 10% stromal infiltration (14 cases); predominantly intraductal carcinoma with 10-49% stromal infiltration (16 cases); infiltrating duct carcinoma with a large component of intraductal growth (50-89% infiltration—26 cases); infiltrating duct carcinoma with minimal intraductal growth (90-99% infiltration—64 cases); and pure infiltrating duct carcinoma with no intraductal component (133 cases). There were no axillary nodal metastases and no tumor-related deaths among the patients with pure intraductal carcinoma, but women whose tumors showed minimal (less than 10%) stromal infiltration had low but significant incidences of metastases and mortality. It appears from the present series and a review of the literature that women with pure intraductal carcinoma (which should be diagnosed only after multiple permanent sections) can safely be treated by less than radical mastectomy, and should have virtually normal life expectancies after treatment. In tumors with increasing proportions of infiltrating growth, there is a progressive increase both in nodal metastases and in mortality. Data are also presented which indicate that, unlike lobular carcinoma of the breast, ductal carcinoma has a very transitory pre-infiltrating phase and may evolve by different mechanisms. Paget's disease of the nipple in this series was never associated with infiltrating carcinomas lacking an intraductal component, and occurred most frequently with predominantly intraductal tumors.

Cyclic 3',5'-adenosine monophosphate phosphodiesterase of Escherichia coli.

Abstract: The cyclic 3′,5′-adenosine monophosphate (c-AMP) phosphodiesterase from Escherichia coli has been partially purified. The enzyme has an apparent molecular weight of 30,000, a Michaelis constant of 0.5 mM c-AMP, and a pH optimum of 7. The partially purified enzyme requires for activity the presence of a reducing compound and of either iron or a protein which seemingly acts as iron carrier.

Pentobarbitone inhibition of catecholamine secretion.

Abstract: Summary 1 The perfused isolated cow adrenal gland was used to investigate the effect of barbituric acid, phenobarbitone and pentobarbitone on catecholamine secretion. 2 Pentobarbitone reduced catecholamine secretion induced by a number of drugs which cause exocytosis. The concentration of pentobarbitone which caused a 50% inhibition of catecholamine secretion was for acetylcholine 5·6 × 10−5m, for carbachol 6·3 × 10−5m, for histamine 1·6 × 10−4m, for (+)-amphetamine 4·4 × 10−5m and for potassium chloride 1·5 × 10−4m. The degree of inhibition by pentobarbitone was not dependent on the concentration of the secretagogue. 3 Pentobarbitone (up to 10−3m) did not inhibit the catecholamine release that was induced by acetyldehyde or by calcium chloride; it inhibited slightly (34%) the catecholamine secretion induced by tyramine. 4 Catecholamine release induced by carbachol was also inhibited by phenobarbitone (50% inhibition at 2·8 × 10−4m (n = 7)) but was unaffected by barbituric acid. 5 Pentobarbitone had no effect on spontaneous or on (+)-amphetamine- or tyramine-induced release of catecholamines from isolated chromaffin vesicles of cow adrenal medulla. 6 It is concluded that pentobarbitone inhibits catecholamine release by preventing a configurational change in the structure of the membrane of the chromaffin cell which is a necessary link between receptor activation and catecholamine release.

A visual, histological, and enzymatic study of regenerating rheumatoid synovium in the synovectomized knee.

Abstract: In the knees of twenty-five patients with rheumatoid arthritis who had had synovectomy an average of thirty-one months previously (range one to 120), arthroscopy, aspiration, and biopsy were done. The findings were that the regenerated synovium became histologically indistinguishable from that found in patients not operated on—grossly and microscopically active areas alternated with inactive ones, lysosomal glycosidases were elevated and rose with time, and the synovium of eighteen of twenty-one of the patients two years after synovectomy met the criteria for rheumatoid disease.

Regulation of the adenosine cyclic 3',5'-monophosphate content of rat cerebral cortex: ontogenetic development of the responsiveness to catecholamines and adenosine.

Abstract: The ontogenetic development of the regulation of adenylate cyclase by adenosine and catecholamines was studied in slices of cerebral cortex of rats from birth to 18 days of age. Incubation of slices in the presence of 100 , µM adenosine did not lead to an increased accumulation of cyclic AMP until the fifth day after birth. The magnitude of the response to adenosine then increased gradually to maximal levels by day 15. In contrast, responsiveness to catecholamines did not develop until 11-12 days after birth, whereupon the system attained maximal responsiveness within 2-3 days. Prior to the development of sensitivity to catecholamines alone, combination of norepinephrine with adenosine resulted in potentiation of the ability of adenosine to increase cyclic AMP levels in the slices. The catalytic activity of adenylate cyclase, measured in cell-free homogenates of rat cortex, was substantial at birth and increased 3-fold by day 20. The results suggest two alternative interpretations: either the adenylate cyclase of rat cerebral cortex undergoes a progressive development of responsiveness to catecholamines or there is a distinct class of adrenergic receptors involved in the potentiative effects of norepinephrine and another class which mediates the effects of norepinephrine alone.

Sulphate Conjugation and L -Dopa Treatment of Parkinsonian Patients

Abstract: CONJUGATION of catecholamines in man was first described for adrenaline by Richter in 19401. He suggested that the conjugated product was an ester of sulphuric acid. Richter and MacIntosh2 later demonstrated that conjugation of adrenaline markedly reduced its presser properties and proposed that conjugation is a mechanism of inactivation of the biological properties of this amine. Holtz and Credner3 administered L-dopa to several animals including man and isolated both free and conjugated dopamine (DA) from urine. Conjugation of two metabolites of DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), was observed by Shaw, McMillan and Armstrong4 when they isolated these two phenolic acids from the urine of human subjects who had received L-dopa orally. The conjugates of these compounds can be isolated by anion exchange chromatography5,6. When conjugated derivatives in the eluates from anion exchange columns were hydrolysed by sulphuric acid5,6 or sulphatase5, the unconjugated parent compounds were identified by paper chromatography.

Ovarian teratoma and neuroglial implants on the peritoneum.

Abstract: The case of an 8 1/2‐year‐old child with a Grade 3 ovarian teratoma is presented. Six months after removal of the tumor, she was found to have a Grade 0 secondary teratoma and Grade 0 glial peritoneal implants. Findings support the concept that the rupture of an ovarian teratoma which contains primitive and multipotential tissues can result in implantation and subsequent development of benign implants and secondary teratomas.

Comparative studies of neurotransmitter substances in the maturing and aging central nervous system of the chicken.

Abstract: Publisher Summary This chapter focuses on some aspects of cholinergic and monoaminergic neurotransmission and the changes occurring during aging. Because the changes occurring during aging are frequently better explained if these changes are compared with early developmental changes, the entire life span was examined. One of the frequent functional characteristics of aging is the slowing of reflex activity, the appearance of tremor-like movements and the loss of short memory. All these phenomena may be attributed to the decline in central nervous system (CNS) neuronal integrative mechanisms with aging. The activities of acetylcholinesterase and choline acetyltransferase, the hydrolyzing and synthesizing enzymes of acetylcholine, were the indices used for cholinergic neurotransmission and endogenous levels of norepinephrine and 5-hydroxytryptamine were indices of monoaminergic neurotransmission. The changes in neurotransmission in the cerebral hemispheres with aging are of importance in view of the role of the cerebral cortex in memory phenomena.