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Senile cardiac amyloidosis: evidence of two different amyloid substances in the ageing heart.

In a material of seventy-two persons over 70 years of age, forty-seven cases of amyloidosis of the heart were found. In thirty-nine cases, deposits occurred only in the atria (isolated artrial amyloidosis, IAA), while in eight cases amyloid also was seen in the ventricles (senile cardiac amyloidosis, SCA). In some of the latter cases, small amyloid deposits occurred in other organs, especially the lungs. Some definite differences existed between the amyloid substance in SCA and IAA. Thus, tryptophan was demonstrated histochemically in SCA but not in IAA, and, furthermore, amyloid fibrils isolated from patients with IAA lacked protein Asca, the fibril subunit protein of senile cardiac amyloid. It is concluded that the ageing heart may be the target of two different forms of amyloid, one only affecting the atria, while the other is more widespread within the heart and sometimes also is found in other organs.

Aged

Growth inhibition of Acinetobacter by 5-chloro-indole-3-acetic acid.

The Acinetobacter calcoaceticus-baumannii complex includes high-priority, multidrug-resistant pathogens for which novel antibiotics are urgently needed. Many bacterial strains from this complex harbor a so-called iac gene cluster that codes for the catabolism of indole-3-acetic acid (IAA). Here, we demonstrate that possession and expression of iac genes represent an Achilles' heel for Acinetobacter species, which can be exploited to suppress bacterial growth by treatment with IAA and its analog 5-chloro-IAA.IMPORTANCEAcinetobacter baumannii is a deadly bacterial pathogen and one of the leading causes of hospital-acquired infections worldwide. It is also known for its resistance to many antibiotics currently available. In this study, we show that Acinetobacter bacteria choke on a mixture of IAA and 5-chloro-IAA, offering a path to the discovery and development of a novel drug treatment.

Indoleacetic Acids

Hill-acitivity and P700 concentration of chloroplasts isolated from radish seedlings treated with-indoleacetic acid, kinetin of gibberellic acid.

The Hill-activity (reduction of DCPIP or methylviolgen) and the concentration of P700 were studied in chloroplasts isolated from cotyledons of radish seedlings (Raphanus sativus L. saxa Treib), which had been grown with the addition of beta-indoleacetic acid (IAA), kinetin, or gibberellic acid. 1) The photosynthetic activity of young chloroplasts from 3 day old Raphanus seedlings is very high (c. 180 micron mol O2/mol chlorophyll X h) and decreases continuously thereafter with increasing age. The steady state Hill-activity is reached after 8 to 10 days (values of 55 to 50 micron mol O2/mg chlorophyll X h). 2) Chloroplasts from plants treated with IAA or kinetin not only exhibit higher plastoquinone levels 1,2, but also a higher P700-content and a higher Hill-activity. The promotion effect is more pronounced with kinetin (+36 tb 40%) than with IAA (+12 to 17%). 3) Gibberellic acid has a different effect on composition and activity of chloroplasts. In younger seedlings the Hill-activity appears to be somewhat stimulated, without promotion effect on plastoquinone 2 or P700 concentration. After 10 days GA3-treated plants show signs of chlorosis combined with a strong decrease in photosynthetic activity. 4) The data clearly demonstrate that the composition and activity of the photosynthetic apparatus are under phytohormone control. IAA and even better kinetin promote the light induced formation of pigment systems and electrontransport chains. GA3 seems to block the rebuilding of the photosynthetic apparatus under steady state conditions.

2,6-Dichloroindophenol

Interruption of the aortic arch. Surgical considerations.

During a 10 year period, January, 1965, through January, 1975, 5 patients with interruption of the aortic arch (IAA) underwent operation at the Texas Heart Institute. The mortality rate was 60 per cent; 2 patients survived the operation. One 11-day-old infant with IAA, type A, a ventricular septal defect (VSD), and a patent ductus arteriosus (PDA) underwent successful two-stage treatment. A left subclavian-ductus anastomosis, closure of the PDA, and banding of the pulmonary artery were done initially. The VSD was closed later. The second survivor, a 3-year-old girl, had IAA, type B, with a PDA and VSD. Total correction was done with the aid of cardiopulmonary bypass and hypothermia. Considerations include palliative and staged procedures versus total correction with either conventional cardiopulmonary bypass or deep hypothermia and circulatory arrest. Survival rate is improved if associated lesions are totally repaired or palliated at the time of reconstruction of IAA.

Aorta

[Deformation of lucerne root hairs caused by the growth substances and culture broth filtrates of Rhizobium meliloti].

Deformation of lucerne root hairs caused by the action of beta-indolylacetic acid (IAA) and alpha-naphthylacetic acid (NAA) differs from deformation induced by Rhizobium meliloti. High concentrations of IAA brought about abnormal deformation of root hairs wherease the action of average concentrations of IAA resulted in corkscrew-like winding and wavy structures. No deformation was observed under the action of low IAA concentrations or the cultural broth of Rhizobium. Infective filaments in root hairs were found only upon infection with pure cultures of Rhizobium.

Acetates

[Effect of benzotriazole derivatives on plant growth. II].

The action on plant growth of sixty benzotriazole derivatives carrying on position 1 or 2 several kinds of substituents, has been studied via the oat coleoptile section elongation test. At medium and low concentrations almost all compounds behave as activators, while at the highest concentrations many of them, like indolylacetic acid (IAA), are growth inhibitors. It is worth noting the lack of toxicity, even at the highest concentration used, for the 1-hydroxyalkylbenzotriazoles and, more generally speaking, the low toxicity of hydroxyalkylbenzotriazoles and of benzotriazolylalkanoic acid amides. In the range of concentration from 10(-6) to 10(-8) M some methylalkylbenzotriazoles as well as some benzotriazolylalkanoic acids and esters are more active than IAA exhibiting from 40 to 60% of the maximal activity of IAA. The activities of methylalkylbenzotriazoles and particularly that of 2-(1'-methyl)pentylbenzotriazole are outstanding; actually at the lowest concentration tested (10(-8) M and at 10(-5) M, at which concentration this compound shows the maximum activity, the biological responses correspond respectively to more than 50 and 80% of maximal activity of IAA.

Edible Grain

NAD(P)H utilization in the reduction of pyruvate to lactate in a glycogen-containing subline of Ehrlich ascites tumour cells.

The possible pathways of utilization of glucose-6-phosphate (G-6-P) produced from glycogen breakdown have been investigated in a glycogen-containing subline of Ehrlich ascites tumour cells. Addition of either mitochondrial inhibitors or pyruvate to ascites cells metabolizing endogenous substrates enhances the rate of lactate production. However, only in the former condition such effect is abolished by iodoacetate (IAA). In pyruvate-supplemented cells mitochondrial inhibitors cause a further increase in lactate production which becomes insensitive to IAA when the cells are depleted of endogenous substrates. Measurements of the glycogen content show that either in the presence of mitochondrial inhibitors or pyruvate there is a stimulation of glycogenolysis. Significant changes (about 10--20 fold increase) of the G-6-P level are observed only in the presence of both mitochondrial inhibitors and IAA, irrespective of pyruvate addition. However, with pyruvate the accumulation of G-6-P becomes lower if the cells are starved. The results obtained indicate that in our conditions G-6-P which is produced during glycogenolysis may be oxidized either through the Embden-Meyerhof pathway or the phosphogluconate pathway. Indeed, whereas mitochondrial inhibitors promote the utilization of this metabolite through the first route by enhancing the activity of phosphofructokinase, added pyruvate favours the other route by lowering the cytosolic NADPH/NADP+ ratio.

Anaerobiosis

Exogenous regulators in the mycelium of Pleurotus ostreatus after exogenous application.

The mycelium of the fungus Pleurotus ostreatus was cultured on a synthetic medium with growth regulators. Best growth was observed on media with 100 ppm IAA, 200 ppm GA3 and 200 ppm of kinetin. Growth of terminal hyphae and the appearance of colonies differed characteristically. Auxin bio-assays showed that the content of substances in younger mycelium slowly increased during cultivation without conspicuous changes in the medium. After exogenous application of IAA the content of auxins in younger mycelium increased and the content of IAA decreased gradually in the culture medium. Gibberellin bio-assays showed their content in the mycelium fell during cultivation and while it increased in the medium. Application of GA3 to the medium leads to a significant increase in these substances in the young mycelium and in the medium their level remains the same. Cytokinin bio-assays showed their content to vary during cultivation. An addition to kinetin to the nutrient medium results in an increase of cytokinins in the mycelium while in the medium the level of cytokinins is maintained. Addition of one substance thus influences the levels of other endogenous regulators.

Agaricales

Endocytosis of Salmonella typhimurium 395 MS and MR10 by HeLa cells.

Monolayer of HeLa cells were examined for their ability to endocytose Salmonella typhimurium 395 MS (wild) and MR10 (chemotype RD). Monolayers treated with the glycolytic inhibitors iodoacetic acid (IAA) or N-ethylmaleimide (NEM) or the respiratory inhibitor sodium azide (NaN3) or cytochalasin B (CB) were incubated with S. typhimurium. The numbers of cell-associated (intracellular plus cell-membrane attached extracellular) and intracellular bacteria were determined by viable counts, together with the HeLa cell ATP levels. IAA and NEM at concentrations 10(-4)M and 10(-3)M decreased significantly the number of intracellular MR10 and the cellular ATP levels, but did not influence significantly the total number of cell-associated bacteria except for 10(-3)M IAA which slightly increased the association. On the other hand, NaN3 at concentrations 10(-4)M and 10(-3)M did not affect the number of associated or intracellular bacteria, or the cellular ATP levels. CB at concentrations of 5, 10 and 20 microgram/ml increased the number of associated bacteria, decreased the number of intracellular bacteria and caused a small decrease in cellular ATP levels. Thus, HeLa cells may internalize S. typhimurium by an energy-requiring, glycolysis-dependent process. CB had a dose-dependent inhibitory effect on the internalization without influencing significantly the HeLa cell ATP levels. This indicates that CB might affect the internalization process by some means other than decreasing the ATP content.

Acetates

The auxin gatekeepers: Evolution and diversification of the YUCCA family.

The critically important YUCCA (YUC) gene family is highly conserved and specific to the plant kingdom, primarily responsible for the final and rate-limiting step for indole-3-acetic acid (IAA) biosynthesis. IAA is an essential phytohormone, involved in virtually all aspects of plant growth and development. In addition, IAA is involved in fine-tuning plant responses to biotic and abiotic interactions and stresses. While the YUC gene family has significantly expanded throughout the plant kingdom, a detailed analysis of the evolutionary patterns driving this diversification has not been performed. Here, we present a comprehensive phylogenetic analysis of the YUC family, combining YUCs from species representing key evolutionary plant lineages. The evolutionary history of YUCs is complex and suggests multiple recruitment events via horizontal gene transfer from bacteria. We identify and hierarchically classify the YUC family into an early diverging grade, five distinct classes and 41 subclasses. Angiosperm YUC diversity and expansion are explained in the context of protein sequence conservation, as well as spatial and gene expression patterns. The presented YUC gene landscape offers new perspectives on the distribution and evolutionary trends of this crucial family, which facilitates further YUC characterization within plant development and response to environmental change.

Indoleacetic Acids

Physiological studies on Phymatotrichum omnivorum. IX. Synthesis of indole acetic acid in vitro.

The cotton root rot fungus, Phymatotrichum omnivorum, synthesized indole acetic acid (IAA) in culture medium containing tryptophan as the only source of nitrogen. Synthesis of IAA was not affected by illumination, and maximum amounts of the auxin were produced at 30 days. The optimum hydrogen ion concentration and temperature for IAA production were 6.5 and 28 degrees C, respectively. Indole ethanol (IEA) was also detected in tryptophan media, primarily during the active growth of the organism.

Culture Media

Intestinal absorption of L-tryptophan in scleroderma.

The purpose of this investigation was to study the intestinal absorption of L-tryptophan and to assess the absorptive function of the intestine in scleroderma. The oral L-tryptophan loading test was performed in 31 cases of systemic scleroderma (progressive systemic sclerosis, PSS) and 3 cases of localized scleroderma. Serum levels of tryptophan and urinary excretion of indole-acetic acid (IAA) and indican (IS) were determined in order to assess intestinal absorption of tryptophan. In 10 cases the D-xylose test and in 4 cases Schilling's test was also performed. Furthermore, in vitro binding of L-tryptophan by plasma proteins in PSS and in other skin diseases as controls was studied. The normal increase in serum tryptophan after loading was noted in 17 cases (in 14 cases of PSS with a mild, slow progression in 3 cases of PSS with a severe, rapidly progressing course). In 10 of these cases, urinary excretion of IAA was higher than normal and in normal and in 3 cases excretion of urinary IS was also above normal. On the other hand, in 14 cases of severe, rapidly progressing PSS and in 2 of 3 cases of widespread linear scleroderma, serum levels of tryptophan were markedly depressed after loading, while urinary excretion of IAA and IS was normal. In all 4 cases studied, Schilling's test was normal, and only in 2 of 10 cases of PSS was the D-xylose test abnormal. It is concluded that in the majority of cases of PSS, intestinal absorpiton of tryptophan is normal as also is the absorptive function of the intestine. The slight rise in serum tryptophan after loading in some cases of PSS may be a result of increased binding of tryptophan by albumin.

Adolescent

Initial clinical trial based on biochemical methodology of zimelidine (a serotonin uptake inhibitor) in depressed patients.

The bicyclic compound Z-1-(4-bromophenyl)-1-(3-pyridyl)-3-dimethylaminopropen (zimelidine) has a pronounced inhibitory effect on neuronal 5-hydroxytryptamine (5-HT) uptake in animals. Zimelidine was given to 6 depressed patients in doses ranging between 25 and 150 mg twice daily for about 3 wk. To get an objective assessment of its pharmacologic effects, the following variables were monitored: (1) plasma levels of parent compound and its desmethylated metabolite; (2) the 5-HT and norepinephrine (NE) uptake inhibiting activity in vitro of plasma drawn from the patients; and (3) the concentrations of the main metabolites of serotonin (5-HT), tryptamine, NE, and dopamine in cerebrospinal fluid (CSF), i.e., 5-hydroxyindoleacetic acid (5-HIAA), indoleacetic acid (IAA), 4-hydroxy-3-methoxyphenylglycol (HMPG), and homovanillic acid (HVA), respectively. Plasma from the patients markedly inhibited 5-HT uptake compared to NE uptake. The inhibitory effect of 5-HT uptake and the plasma concentration of the desmethylated metabolite correlated significantly. The 5-HIAA levels in CSF decreased markedly in 4 patients while the IAA levels increased. The levels of HMPG also decreased significantly, but less so than the 5-HIAA levels. The effects on HVA were inconsistent. Zimelidine appears to be a selective inhibitor of 5-HT uptake in central monoamine neurons and is therefore an interesting pharmacologic tool in future central nervous system (CNS) research.

Animals

Fast axonal transport: effect of antimitotic drugs and inhibitors of energy metabolism on the rate and amount of transported protein in frog sciatic nerves.

Mitosis inhibitors, drugs affecting the energy metabolism, heavy water, and ouabain were used to partially inhibit fast axonal transport in frog sciatic nerves. Effects on the rate and on the amount of pulse labeled protein could be separated. The pulse of labeled protein, released after a cold-block, rapidly reached a maximum height which indicated that the transport system was saturated in the nerve segment occupied by the pulse. Both the rate and the amount were reduced by the mitosis inhibitors colchicine, vinblastine, and griseofulvin. Colchicine had a differential effect and reduced the rate of material migrating in the advancing front of the pulse less than the rate of that moving in the peak. Preincubation at low temperature potentiated the effects of colchicine. Two inhibitors of energy metabolism, NaCN and IAA, reduced the amount of labeled material in the pulse. The slope of the pulse was markedly reduced and multiple peaks appeared. The distance covered by the migrating pulse was largely unaffected, but some retardation of late components might have occurred. In contrast, 2.4-DNP reduced the rate without any effects on the amount of migrating material. Heavy water uniformly reduced the rate of the migrating pulse, whereas the main effect of ouabain was a diminished amount and multiple peaks as with NaCN and IAA. All drugs were tested for their effects on the electrical activity of sciatic nerves. The compound action potential was not affected by the mitosis inhibitors and heavy water, but was depressed by the inhibitors of energy metabolism and abolished by ouabain. The results indicate that the effects of various transport inhibitory drugs can be differentiated if both the rate and the amount are considered.

Action Potentials

Tension responses of frog sartorius muscle to quick ramp-shaped shortenings and some effects of metabolic inhibition.

The dynamic properties of the contractile mechanism of skeletal muscle were investigated in electrically stimulated sartorius muscle of the frog at 0 degrees C by analysis of the force responses to quick changes in length. 1. The tension responses to ramp-shaped shortenings at different rates of shortening have been recorded. The tension course during the ramp is described in terms of a damped elastic element. In addition a maximum value for an additional series elastic element is estimated. 2. The tension reponses to pulse-shaped shortenings have been recorded. At least 15 ms after the pulse a minimum in tension is found, which depends on amplitude and duration of the pulse. This effect is optimal at a pulse duration of about 6 ms. It is concluded that within 15 ms after the pulse detachment of crossbridges occurs. 3. Muscles were incubated with the metabolic inhibitors IAA and FAA or IAA and FDNB. After repeated stimulation, but before the muscle passes into the rigor state, the fast recovery and the plateau in the responses to quick shortenings are either diminished or abolished, depending on the amplitude of the shortening. This can be explained by assuming that in the unpoisened muscle, ATP enables the crossbridges to exert temporarily a larger force.

Adenosine Triphosphate

Regulation of calcium transport in isolated periosteal cells, effects of hormones and metabolic inhibitors.

Calcium transport was studied in cells isolated from cultured periostea of 18-day-old chick embryos. Net calcium uptake was stimulated by iodoacetate (IAA) and inhibited by dinitrophenol (DNP). Calcium efflux from the intracellular compartment was inhibited by IAA. Changes in the extra- or intracellular sodium concentration had only minor effects on calcium transport. This indicates that calcium efflux from periosteal cells is probably directly dependent on ATP hydrolysis, whereas calcium-sodium exchange is of less importance. The cation ionophore A23187 stimulated calcium uptake during short incubations but was inhibitory in long incubations. The possible involvement of the mitochondria in this effect is discussed. Parathyroid hormone (PTH) and calcitonin (CT) stimulated the net uptake of calcium in relatively low doses (both 0.01 U/ml or higher). The effects of the hormones on net calcium uptake were not additive. Calcium efflux was not changed in the presence of PTH or CT.

Animals

Defined conditions for the initiation and growth of cotton callus in vitro. I. Gossypium arboreum.

Defined in vitro conditions for callus initiation by Gossypium arboreum L. were determined, and different tissues were evaluated as explant sources, Environmental conditions tested included light versus dark, and low light versus high light. Different nutrient media as well as carbohydrate sources were examined. Our data show that hypocotyl tissue was superior to cotyledon or leaf tissue as the explant source for callus proliferation; the Murashige-Skoog inorganic formulation with (in mg per 1) 100 myo-inositol, 0.4 thiamine-HCl, 2 indoleacetic acid (IAA), 1 kinetin, and 3% glucose solidifield by agar was the best medium to initiate callus. Cultures with sucrose as a carbohydrate source browned rapidly. Callus proliferation was superior under high light (8000 to 9000 lux) conditions at 20 +/- 1 degree C. Various combinations of auxins and cytokinins were tested for their ability to improve callus proliferation and subsequent growth of subcultures. Although the MS medium containing IAA and kinetin was found superior for obtaining rapid proliferation of callus from hypocotyl explants, a second medium containing 2 mg per 1 naphthaleneacetic acid (NAA) and 0.5 to 1 mg per 1 benzyladenine (BA) was found necessary for vigorous growth of subcultured callus. A MS medium with 5 to 10 mg per 1 N6-[delta2-isopentenyl]-adenine (2ip) and 1 mg per 1 NAA was also favorable for continued subculturing.

Ascorbic Acid

Studies on the biochemical aspects of the 'disulfiram-like' reaction induced by oral hypoglycemics.

In vitro experiments, using rat liver homogenates, were designed to examine certain of the proposed enzymatic mechanisms for the interaction of oral hypoglycemic drugs with monoamine and ethanol metabolism. The oxidative degradation of tryptamine was studied by measuring indoleacetic acid (IAA) production and conclusions were drawn with regard to the activity of monoamine oxidase, aldehyde dehydrogenase and ethanol dehydrogenase. Acetohexamide, hydroxyhexamide, tolazamide, tolbutamide and chlorpropamide failed to reveal any specific inhibition of the three enzymes. Ethanol (0.2% w/v) and disulfiram decreased IAA formation, as did a lack of available aldehyde dehydrogenase and NAD, but these reductions were not enhanced by the hypoglycemic agents. The results suggest that the 'disulfiram-like' reaction which occurs in certain patients imbibing ethanol while receiving oral hypoglycemic drugs, depends upon some factor(s) other than, or additional to, a specific interference with monoamine and/or ethanol metabolism.

Administration, Oral