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Biomedical subjects

T Baum

Publications and source records attributed to T Baum.

At least 19 recordsLinked to original sources

Sex-dependence of the relative number of elastic fibres in human heart valves.

The aim of the current study was to find out whether there are sex-dependent differences in the relative number of elastic fibres in human heart valves. Twenty-six aortic valves, 26 mitral valves, 33 pulmonary valves and 28 tricuspid valves of both sexes were obtained at autopsy from newborn to 89-year-old patients who died of noncardiac diseases. The quantitatively morphometric investigations were carried out on conventionally stained (Resorcinfuchsin) histological sections. The results were qualitatively examined with immuno-histochemically marked (anti-elastin antibodies) histological sections. Earlier examinations by Leutert [1976. Z. Gesamte Inn. Med. 31, 97-104] showed that the atrioventricular valves have the following layers: endothelium, atrial fibroelastic tissue (S1), fibrous tissue, ventricular fibroelastic tissue (S2) and endothelium. In our study, the ventricular side of the semilunar valves corresponds to side S1, whereas the vessel side corresponds to side S2. Three regions of interest were examined on each side of the valves: base, mid and tip. The number of elastic fibres per measuring area for all four human heart valves was significantly higher (p < 0,001) in fibroelastic tissue of side S1 than in fibroelastic tissue of side S2. Neither on side S1 nor on side S2 were there significant gender-related differences in the relative number of elastic fibres per measuring area. The results suggest a characteristic distribution of the elastic fibre system which is not sex-dependent but closely related to the function of the heart valves.

Adolescent↗

In planta localization of a beta-1,4-endoglucanase secreted by Heterodera glycines.

Polyclonal sera specific to beta-1,4-endoglucanases (cellulases) synthesized in the subventral esophageal gland cells of the soybean cyst nematode, Heterodera glycines, were used to provide the first identification of a nematode esophageal gland protein that is secreted into host plant tissue. Sera generated to proteins encoded by Hg-eng-1 and Hg-eng-2 (endoglucanases) did not cross-react with soybean root proteins on Western blots (immunoblots) or in immunofluorescence microscopy of noninoculated (control) soybean root sections. In cross sections of soybean roots at 24 h after inoculation of roots with second-stage juveniles of H. glycines, HG-ENG-1 was localized within the nematode's subventral gland cells and was not detected in root tissue. HG-ENG-2 was localized within the subventral gland cells and was secreted from the juvenile's stylet into root cortical tissue at 24 h after inoculation of roots with second-stage juveniles of H. glycines. HG-ENG-2 was localized along the juvenile's migratory path through the root cortex.

Animals↗

Upper respiratory symptoms in elderly patients. Hypertension complicates treatment decisions.

Approximately 6% of elderly patients present to primary care offices with hypertension and upper respiratory infection. Elderly people develop an acquired immunity to many rhinoviruses, making them less susceptible than younger people to the common cold. But because of the decreased vigor of their immune systems, they are less able to fight infection, particularly secondary bacterial infections. Upper respiratory infections require close monitoring in elderly patients to detect secondary infections and other complications. Most published research on respiratory symptom treatment is not limited to elderly subjects.

Aged↗

Genomic organization of four beta-1,4-endoglucanase genes in plant-parasitic cyst nematodes and its evolutionary implications.

The genomic organization of genes encoding beta-1,4-endoglucanases (cellulases) from the plant-parasitic cyst nematodes Heterodera glycines and Globodera rostochiensis (HG-eng1, Hg-eng2, GR-eng1, and GR-eng2) was investigated. HG-eng1 and GR-eng1 both contained eight introns and structural domains of 2151 and 2492bp, respectively. HG-eng2 and GR-eng2 both contained seven introns and structural domains of 2324 and 2388bp, respectively. No significant similarity in intron sequence or size was observed between HG-eng1 and HG-eng2, whereas the opposite was true between GR-eng1 and GR-eng2. Intron positions among all four cyst nematode cellulase genes were conserved identically in relation to the predicted amino acid sequence. HG-eng1, GR-eng1, and GR-eng2 had several introns demarcated by 5'-GCellipsisAG-3' in the splice sites, and all four nematode cellulase genes had the polyadenylation and cleavage signal sequence 5'-GAUAAA-3'-both rare occurences in eukaryotic genes. The 5'- flanking regions of each nematode cellulase gene, however, had signature sequences typical of eukaryotic promoter regions, including a TATA box, bHLH-type binding sites, and putative silencer, repressor, and enhancer elements. Database searches and subsequent phylogenetic comparison of the catalytic domain of the nematode cellulases placed the nematode genes in one group, with Family 5, subfamily 2, glycosyl hydrolases from Scotobacteria and Bacilliaceae as the most homologous groups. The overall amino acid sequence identity among the four nematode cellulases was from 71 to 83%, and the amino acid sequence identity to bacterial Family 5 cellulases ranged from 33 to 44%. The eukaryotic organization of the four cyst nematode cellulases suggests that they share a common ancestor, and their strong homology to prokaryotic glycosyl hydrolases may be indicative of an ancient horizontal gene transfer.

3' Untranslated Regions↗

[From nuclear spin tomography image to a surface model].

This paper describes a computer-aided procedure for creating a surface model on the basis of pattern recognition in images produced by nuclear spin tomography. A local search algorithm that recognizes the entire profile of the relevant object starting from a point determined (input) by the user is described. The pattern (structure) thus recognized is approximated by a mathematical description. By including the adjacent layers, a surface model can be generated. The main focus is on the rapid identification of the pattern and the prior preparation of the data used as input for the surface model. The human shoulder serves as an example to verify the approach.

Algorithms↗

Effects of ambient ozone on respiratory function and symptoms in Mexico City schoolchildren.

The effects of ambient ozone (O3) on respiratory function and acute respiratory symptoms were evaluated in 143 7- to 9-yr-old schoolchildren followed longitudinally at 1- to 2-wk intervals over a period of 6 months at three schools in Pedregal, Mexico City. The maximum O3 level exceeded the World Health Organization guideline of 80 ppb and the U.S. standard of 120 ppb in every week. For an increase from lowest to highest in the mean O3 level during the 48 hr before spirometry (53 ppb), logistic regression estimated relative odds of 1.7 for a child reporting cough/phlegm on the day of spirometry. For the full population, the mean O3 level during the hour before spirometry, not adjusted for temperature and humidity, predicted a significant decrement in FVC but not in FEV1 or FEF25-75. In contrast, the mean O3 level during the previous 24-, 48-, and 168-h periods predicted significant decrements in FEV1 and FEF25-75 but not in FVC. Ozone was consistently associated with a greater decrement in lung function for the 15 children with chronic phlegm as compared with the children without chronic cough, chronic phlegm, or wheeze. Ozone in the previous 24-, 48-, and 168-h periods predicted decrements in FEV1 for children of mothers who were current or former smokers, but not for children of mothers who were never smokers. Many of these effects were reduced in multiple regression analyses including temperature and humidity, as temperature and O3 were highly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗

LY171883 preserves mesenteric perfusion in porcine endotoxic shock.

Superior mesenteric arterial perfusion (Q) decreases and gut intramucosal hydrogen ion concentration, [H+], increases in resuscitated normodynamic endotoxic pigs. The present study tested the hypothesis that these adverse phenomena can be prevented by pretreatment with LY171883, a specific leukotriene (LT) D4/E4 receptor antagonist. Pentobarbital-anesthetized pigs (14-18 kg) were instrumented to permit measurement of Q (ultrasonic flow probe) and [H+] (tonometer). Mesenteric O2 delivery (DO2) and consumption (VO2) were calculated from the O2 contents of arterial and superior mesenteric venous blood. At t = -20 min, groups (N = 6) of pigs were pretreated witH LY171883 (10 mg/kg) or vehicle. At t = 0 min, the pigs were infused over 20 min with lipopolysaccharide (LPS; 150 micrograms/kg) and resuscitated for 2 hr with saline (1.2 ml/kg min). Irrespective of treatment group, mean arterial pressure and systemic vascular resistance index decreased significantly after infusion of LPS. In general, cardiac index (CI) was well preserved, although in controls at t = 20, 100, and 120 min, CI decreased significantly with respect to the t = 0 min value. Normal mesenteric Q and DO2 were maintained in the LY171883 group, whereas, in controls, these parameters decreased significantly. Mesenteric VO2 increased transiently but significantly in controls; this phenomenon was abrograted by the LT receptor antagonist. In controls, intramucosal [H+] increased by almost threefold; this adverse effect was significantly ameliorated by LY171883. These data suggest that decreased mesenteric Q and increased intramucosal [H+] may be mediated by LT in this porcine endotoxic shock model.

Acetophenones↗

Angiotensin converting enzyme inhibitors: spirapril and related compounds.

The synthesis of spirapril (5), spiraprilat (25), their RSS stereoisomers, and their glycyl (18b) and lysyl (36, 37) analogues is described. These compounds were evaluated in vivo for inhibition of angiotensin converting enzyme (ACE), and selected compounds were evaluated for in vitro ACE inhibition (spirapril ID50 16 micrograms/kg; spiraprilat IC50 0.8 nM, ID50 8 micrograms/kg). In anesthetized rats, iv, esters 5 and 36 are more potent than enalapril, and diacids 25 and 37 are more potent than enalaprilat in vitro. In the conscious rats, orally, 5 and enalapril (2) showed potent and sustained activity at doses of 0.03-1 and 0.1-1 mg/kg, respectively. From this work, spirapril was selected for clinical evaluation as an antihypertensive agent.

Angiotensin-Converting Enzyme Inhibitors↗

Synthesis and pharmacological activity of angiotensin converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines.

The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.

Angiotensin-Converting Enzyme Inhibitors↗

Systemic effects resulting from topical ocular administration of SCH 33861, a novel ACE inhibitor ocular hypotensive agent.

SCH 33861 (7- N- 1(S)-(Carboxy)-3-phenylpropyl -(S)-alanyl 1,4-dithia-7-azaspiro 4.4 nonane-8(S)-carboxylic acid) is a novel, non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with marked topical ocular hypotensive activity. The present study evaluated the degree of systemic ACE inhibition resulting from topical administration of 0.01 and 0.1% concentrations (10 and 100-fold greater than needed to lower IOP) of SCH 33861 in conscious rabbits. For reference purposes, captopril, a prototype ACE inhibitor, was examined at concentrations 5 and 20-fold greater than needed to lower IOP. Neither 0.01 nor 0.1% topical SCH 33861 led to inhibition of pressor responses to 0.3 micrograms/kg iv challenges with angiotensin I (AI) over a 4 hr period. Captopril, in contrast, caused significant attenuation of AI pressor responses. The magnitude and duration of systemic ACE inhibition following captopril administration was concentration related. Intravenous administration of the same dose administered topically did not cause any systemic ACE inhibition with 0.01% SCH 33861. Following iv 0.1% SCH 33861, 0.5 or 2.0% captopril, AI responses were inhibited 60-70% indicating the ability to inhibit ACE if any systemic absorption took place. Topical administration of 0.01% SCH 33861 twice daily for five days also did not produce systemic ACE inhibition. These findings indicate that topical amounts of SCH 33861 greatly in excess of those needed to effect reductions in IOP have an exceptionally low potential for producing systemic effects.

Administration, Topical↗

Topical ocular hypotensive effects of the novel angiotensin converting enzyme inhibitor SCH 33861 in conscious rabbits.

SCH 33861 is a novel, non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor. Topical administration of the compound to the eye of conscious rabbits was employed to examine actions on intraocular pressure (IOP). Falls in IOP resulted from SCH 33861 (0.001-0.01%) administration. Ocular hypotensive responses were sustained for as long as 24 hrs following a single application of 0.001% SCH 33861. The RSS isomer of SCH 33861, which is 200-fold weaker an ACE inhibitor than SCH 33861, caused only transient falls in IOP at 0.1% concentration. The magnitude of the fall in IOP induced by 0.001% SCH 33861 (4.8 +/- 0.5 mmHg) was comparable to that produced by 0.5% timolol (4.5 +/- 0.3 mmHg). Other ACE inhibitors such as captopril (0.1%) and enalaprilic acid (0.01%) also reduced IOP by 4.0 +/- 0.4 and 4.7 +/- 0.4 mmHg, respectively. These findings indicate that SCH 33861 is 500-fold more potent on a weight basis than is timolol in lowering IOP. No loss of ocular hypotensive activity was observed when SCH 33861 was administered twice daily for 5 days suggesting little, if any, potential for tolerance development. SCH 33861, as well as the other ACE inhibitors, caused neither ocular irritation nor alteration of pupil diameter. These findings suggest that inhibition of ocular ACE may represent an effective means of reducing IOP.

Administration, Topical↗

Pharmacologic, metabolic, and toxicologic profile of spirapril (SCH 33844), a new angiotensin converting inhibitor.

Spirapril (SCH 33844; 7-N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-(S)-alanyl-1,4-dithia- 7-azaspiro[4,4]-nonane-8(S)-carboxylic acid) is a new angiotensin-converting enzyme (ACE) inhibitor. SCH 33844 diacid inhibited hydrolysis of hip-his-leu by rabbit lung ACE in a potent (Ki = 0.74 nM), selective, and noncompetitive fashion. SCH 33844 (0.03-1 mg/kg p.o.) produced dose-related inhibition of angiotensin I (AI) pressor responses in conscious rats with a duration of 24 h at the higher dose. SCH 33844 (0.3-30 mg/kg p.o.) reduced blood pressure in a dose-related manner in conscious SHR with a 24-h duration. Antihypertensive activity was enhanced in the presence of hydrochlorothiazide. The drug (1-10 mg/kg p.o.) also lowered blood pressure in conscious hydrochlorothiazide-treated normotensive dogs. In anesthetized dogs, SCH 33844 (1 mg/kg i.v.) reduced blood pressure and total peripheral vascular resistance and slightly increased cardiac output and stroke volume. These results suggest that peripheral vasodilation is the primary mechanism of the antihypertensive action. The metabolic profile of SCH 33844 was evaluated in dogs and rats. The compound was absorbed in a dose-proportional manner and excreted primarily as the diacid form. In contrast to captopril and enalapril, most of the drug (67%) was excreted into the feces following i.v. dosing. Chronic toxicological evaluation in dogs and rats demonstrated that the drug was relatively devoid of toxicity at oral doses as high as 400 and 450 mg/kg/day, respectively. Slight decreases in heart weight (rats) and increases in granularity of the juxtaglomerular apparatus were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Antihypertensive, hemodynamic and autonomic profile of a new angiotensin converting enzyme inhibitor, SCH 33844 (spirapril).

SCH 33844 is a new, potent and long-acting inhibitor of angiotensin converting enzyme (ACE). Antihypertensive, hemodynamic and autonomic actions of SCH 33844 were examined in the present series of experiments. Oral administration of 0.3-30 mg/kg reduced blood pressure of spontaneously hypertensive rats. The magnitude of the response was significantly enhanced by pretreatment of the animals with hydrochlorothiazide. Blood pressure remained significantly depressed 24 hr following doses of 3 and 10 mg/kg. Administration of SCH 33844 (3 mg/kg) twice daily to nonpretreated rats or once daily to diuretic-pretreated animals for 5 days resulted in a progressive decrease in blood pressure. The compound did not reduce blood pressure in nephrectomized rats demonstrating the dependence of its action on renal renin. SCH 33844 (1-10 mg/kg orally) also produced dose-related decreases in pressure in diuretic-pretreated conscious normotensive dogs. However, only a small fall in pressure occurred in non-pretreated dogs. Hemodynamic actions were examined in anesthetized dogs. SCH 33844 (1 mg/kg i.v.) reduced blood pressure, increased cardiac output and caused a large fall in peripheral resistance. Autonomic actions were assessed in pithed rats. The compound (10 mg/kg orally) tended to decrease pressor responses to sympathetic activation and to i.v. norepinephrine. This profile is probably due, at least in part, to vasorelaxation following suppression of angiotensin II generation. In conclusion, SCH 33844 is a potent, long-lasting antihypertensive agent which reduces peripheral vascular resistance and possesses only slight autonomic effects.

Adrenergic Agonists↗

Angiotensin converting enzyme inhibitory activity of SCH 33844 (spirapril) in rats, dogs and monkeys.

SCH 33844 is a new non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor. SCH 33844 diacid inhibited hydrolysis of the synthetic substrate hippuryl-histidyl-leucine by rabbit lung ACE in vitro with an IC50 (concentration inhibiting enzyme by 50%) of 0.81 nM. The ester was 83 times less active. Intravenous administration of SCH 33844 and its diacid inhibited pressor responses to angiotensin I (AI) in anesthetized rats with calculated ID50's of 16 and 8 micrograms/kg, respectively. Oral administration of SCH 33844 (0.03-1 mg/kg) inhibited AI pressor responses in conscious rats with a duration of 24 hr at the highest dose. The diacid was inactive. Intravenous administration of SCH 33844 (100-1000 micrograms/kg) or its diacid (30 micrograms/kg) to anesthetized dogs inhibited AI pressor activity and potentiated the depressor response to bradykinin. SCH 33844 inhibited AI responses in conscious dogs following oral administration of 0.3-3 mg/kg. Oral administration of SCH 33844 (1 mg/kg) to conscious monkeys inhibited AI pressor responses for the 4 hr duration of study. In conclusion, SCH 33844 is a potent, orally effective ACE inhibitor in rats, dogs and monkeys.

Angiotensin I↗

Analysis of vascular responses in rat hindquarters arterial resistance vessels and veins in situ.

The venous compartment plays a critical role in circulatory control. The present series of experiments was conducted to assess simultaneously effects of vasoactive drugs on arterial resistance and venous capacitance vessels of the rat hindquarters perfused with physiological salt solutions (SS). Retrograde infusion of SS into rat hindquarters via the vena cava resulted in an increase in hindquarters venous pressure (Pv). The range of mean volumes required to increase Pv to 20 and 30 mm Hg was 1.7 +/- 0.1 to 2.9 +/- 0.4 and 3.8 +/- 0.3 to 6.9 +/- 0.3 ml, respectively, in various groups of rats during a control period. Perfusion of the hindquarters with an SS containing 80 mM K+ reduced the volume required to increase Pv to 20 and 30 mm Hg to 47 +/- 2 and 42 +/- 2% of control, respectively, indicating venoconstriction. K+ (80 mM) SS also increased aterial perfusion pressure (Pa; measured from a sidearm off of the inflow catheter) to 141 +/- 9 mm Hg, indicating arterial vasoconstriction. Arterial and venous responses to 80 mM K+ were attenuated markedly by perfusion with SS containing zero Ca and 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, indicating dependence on extracellular Ca. Phentolamine (10(-5) M) attenuated the arterial and venous response to 80 mM K+, indicating an alpha adrenergic contribution. Arterial responses to 80 mM K+ were attenuated markedly by the Ca entry blockers nifedipine (10(-6) and 10(-5) M) and verapamil (10(-6) and 10(-5) M). In contrast, venous responses were not affected by nifedipine and were reduced slightly only at the high concentration of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

AGEPC, a vasodilator phospholipid with profound circulatory actions.

Acetyl-glyceryl-ether-phosphoryl-choline (AGEPC) is a potent platelet activating factor which induces profound circulatory changes. AGEPC is synthesized in a variety of cell types including platelets, neutrophils, macrophages, basophils and endothelial cells. Biological responses include platelet activation, neutrophil activation, release of arachidonic acid metabolites and systemic anaphylaxis. Circulatory responses to AGEPC were evaluated in the present investigation. Intravenous administration of AGEPC (30 micrograms/kg/min) to anesthetized dogs reduced blood pressure, cardiac output, myocardial contractile force, renal blood flow and glomerular filtration. Intracoronary administration of AGEPC (0.3-3 micrograms) reduced blood pressure, coronary blood flow, and myocardial contractile force. Administration of AGEPC into the femoral vascular bed increased femoral artery blood flow. The data suggest that the circulatory response to AGEPC in the dog is complex and depends on the site of administration. The predominant response is hypotension mediated at least in part through myocardial depression. Intramuscular injection of AGEPC (10-30 micrograms/kg) to conscious spontaneously hypertensive rats (SHRs) reduced systemic blood pressure and increased heart rate. In pithed rats, AGEPC decreased pressor responses to sympathetic stimulation, angiotensin II and phenylephrine. Chronotropic responses were unchanged. Thus, antihypertensive doses of AGEPC reduced pressor responsiveness nonspecifically, but do not affect pre- or post-junctional adrenergic mechanisms. High concentrations of AGEPC (100 microM) relaxed phenylephrine contracted rabbit aortic rings. Relaxation was dependent on an intact endothelium. Lyso-GEPC produced similar actions. In light of the low potency of AGEPC and the activity of lyso-GEPC, physiological significance to endothelium dependent relaxation by AGEPC in rabbit aortic rings is unlikely. The physiological role of AGEPC in circulatory homeostasis is unclear at present. AGEPC may play a hypotensive role in some forms of experimental hypertension. In addition, AGEPC may mediate part of the circulatory derangements associated with cardiac anaphylaxis. Lastly, AGEPC may be involved in circulatory control during states of platelet and/or neutrophil activation such as myocardial ischemia and shock.

Animals↗

Comparative effects of SCH 19927 and timolol on intraocular pressure of conscious rabbits and relative systemic beta-blockade resulting from topical administration.

SCH 19927, the RR isomer of labetalol, has been shown to possess beta-blocking and vasodilator properties. It was compared to timolol for ability to lower intraocular pressure (IOP) in conscious rabbits. Its potential for systemic beta-blockade after topical administration was also assessed. Dose-related reductions in IOP followed topically applied SCH 19927 (0.1-1.0%). Timolol in concentrations less than 0.5% was not effective in lowering IOP. Timolol (0.1 and 0.5%) strongly inhibited tachycardia induced by iv isoproterenol. A 1.0% concentration of SCH 19927 was less effective than 0.5% timolol in inhibiting the isoproterenol-induced tachycardia; 0.1% SCH 19927 caused only minor inhibitory actions. Thus, not only is SCH 19927 at least as potent in lowering IOP in conscious rabbits, its topical administration results in less systemic beta-blockade than does timolol.

Animals↗