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Biomedical subjects

R D Smith

Publications and source records attributed to R D Smith.

At least 415 records · Page 23Linked to original sources
PubMed1982

Serologic evidence of Anaplasma marginale infection in Illinois white-tailed deer.

A total of 175 deer and 54 cattle from Crab Orchard National Wildlife Refuge in southern Illinois were tested for antibody to Anaplasma marginale, using the capillary tube agglutination test. A total of 12 (6.9%) deer and 7 (13%) cattle were serologically positive. Serologic prevalence in deer increased from 0 at 6 months of age to 14% at 2 1/2 or more years of age. Cattle less than approximately 1 year of age were not seropositive.

Anaplasmosis↗
PubMed1982

Paganini's hand.

Explore the source record for details and available documents.

Hand↗
PubMed1982

Elevated blood pressure following LHRH antagonists in rats.

LHRH and three potent antagonistic analogs: z-[Gln1, des-His2,D-Pse6,des-Gly10]-LHRH ethylamide, where D-Pse = threo-D-phenylserine; z-[Gln1,des-His2,D-Phe6,des-Gly10]-LHRH ethylamide; and Boc-[Ser(Bzl)1,des-His2,D-Trp6]-LHRH; were studied for their effects on blood pressure and heart rate in chronically catheterized conscious normotensive and hypertensive rats. All three analogs caused acute increases in blood pressure in normotensive male Sprague-Dawley rats; the z-Gln-Phenylalanine derivative also raised blood pressure in spontaneously hypertensive rats of Kyoto-Wistar origin. LHRH itself had no effect in either normotensive or hypertensive animals. The antagonistic analogs were also associated with acute toxicity. It is concluded that the antagonist analogs of LHRH, unlike LHRH itself, have significant acute cardiovascular effects in rats. Although the mechanism of these effects is not known nor is it known whether they occur in other species, the present data emphasize the need to define further the pharmacological profiles of these potent, biologically active materials.

Animals↗
PubMed1982

Angiotensin converting enzyme inhibitors: modifications of a tripeptide analogue.

Modified nonhydrolyzable tripeptide analogues of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline (1), designed to impart oral angiotensin converting enzyme (ACE) inhibitory activity, were made and evaluated in vivo and in vitro. The N-methyl and C5-methyl analogues of 1 were inactive. Insertion of heteroatoms (O, S, NH) into the C--C chain of 1 gave a series of compounds with high in vitro activity in the guinea pig serum ACE assay. The O-analogue was the most potent with an IC50 = 4.4 x 10(-9) M compared to 1 with an IC50 = 3.2 x 10(-9) M. The structure-activity relationships in this series of compounds lead one to speculate that the heteroatom provides an additional binding site to the surface of the enzyme; however, these compounds were inactive when tested for antihypertensive activity in the renal hypertensive rat at 30 mg/kg by the oral route (captopril is active at 1.0 mg/kg po).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline: effect of changes at positions 2 and 5 of the hexanoic acid portion.

Several derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and tested for converting enzyme inhibition activity and blood pressure lowering effects in rats. One compound, 5(S)-benzamido-2(R)-methyl-4-oxo-6-phenylhexanoyl-L-proline (2a), had and I50 against angiotensin converting enzyme of 1.0 x 10(-9) M and is the most potent inhibitor prepared thus far in this class of compounds. Testing of 2a orally at 30 mg/kg for inhibition of the angiotensin I induced blood pressure increase in conscious normotensive rats gave 100% inhibition that required 143 min before the angiotensin I blood pressure response returned to 70% of the pretreatment control response. In the conscious renal hypertensive rat, 2a given orally at a dose of 3 mg/kg caused a lowering of blood pressure that reached its maximum of 40 mmHg 8 h following drug administration.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

'Routine' stains on osmicated resin embedded hepatic tissue.

The recently described modification of the osmium tetroxide method for demonstrating lipid can be used on liver biopsies taken for diagnostic purposes. An unstained section is used for the quantitation of the lipid and sequential sections can be stained by all the 'routine' liver stains.

Animals↗
PubMed1982

Cyclic sequential compression of the lower limb in prevention of deep venous thrombosis.

Patients undergoing operations on the hip for either replacement or fracture were chosen for this study. Fifty-two subjects received cyclic sequential compression as well as elevation of the lower limb while another fifty-two patients were treated with only elevation of the lower limb. No other method of prophylaxis for deep venous thrombosis was employed during the study period. Support stockings were used after removal of the compression device. Doppler ultrasound, phleborheography, and, when possible, radioiodinated fibrinogen scanning were used for identification and location of thrombi. A deep-vein thrombosis developed in ten patients (19 per cent) in the control group and in only one patient (2 per cent) in the group that was treated with compression. This difference is statistically significant (p less than 0.05).

Aged↗
PubMed1981

Bovine babesiosis: protection of cattle with culture-derived soluble Babesia bovis antigen.

Adult Hereford (Bos taurus) cattle were protected from severe reactions and death caused by the tick-borne protozoan hemoparasite Babesia bovis, 3 months after vaccination with a cell culture--derived immunogen. The immunogen consisted of filtered, freeze-dried supernatant fluid collected from long-term cultures of Babesia bovis in vitro. It was reconstituted with saponin adjuvant and injected twice subcutaneously at 2-week intervals. Serum collected from vaccinated cattle caused thickening of the merozoite surface coat, aggregation, and lysis of merozoites in vitro. This reaction was identical to that caused by serum from immune carrier cattle suggesting that the protective antigen present in culture fluids is merozoite surface coat antigen. No mortality occurred among vaccinated cattle, whereas mortality among unvaccinated cattle and Babesia bigemina--immune cattle was 62.5 percent indicating that immunity to bovine babesiosis is species-specific.

Animals↗
PubMed1981

Synthesis and angiotensin-converting enzyme inhibitory activity of 3-(Mercaptomethyl)-2-oxo-1-pyrrolidineacetic acids and 3-(Mercaptomethyl)-2-oxo-1-piperidineacetic acids.

A number of gamma- and delta-lactam derivatives were synthesized and their in vitro angiotensin-converting enzyme (ACE) inhibitory activities were compared. The structures of these compounds were designed to include many of the important features of captopril. The synthesis involved the preparation of a variety of novel 3-methylene-2-pyrrolidinones (3-5 and 16) and 3-methylene-2-piperidinones (3a-5a, 10-12, and 17). The key intermediate 3-methylenelactams 3 and 3a were obtained from 3-(hydroxymethyl)lactams 2 and 2a by a direct dehydration with dicyclohexylcarbodiimide using cuprous iodide as a catalyst. Introduction of the sulfhydryl group was accomplished by a Michael addition of these alpha, beta-unsaturated lactams. The compound with the highest in vitro activity was 3-(mercaptomethyl)-2-oxo-1-piperidineacetic acid (7a). The activity of the 7a both in vitro and in vivo (dog) was shown to be less than that of captopril by a factor of about 100.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1981

Antihypertensive activity of 6-arylpyrido[2,3-d]pyrimidin-7-amine derivatives.

A series of 51 6-arylpyrido[2,3-d]pyrimidin-7-amine derivatives was prepared and evaluated for antihypertensive activity in the conscious spontaneously hypertensive rat. A number of these compounds, notably 6-(2,6-dichlorophenyl)-2-methylpyrido[2,3-d]pyrimidin-7-amine (36), lowered blood pressure in these rats in a gradual and sustained manner to normotensive levels at oral doses of 10-50 mg/kg. Normalized blood pressure levels could then be maintained by single daily oral doses. The effect of structural variation in the 6-aryl group and in the 2 and 4 positions of the pyridopyrimidine ring on activity is reported and discussed.

Animals↗
PubMed1981

Novel synthesis of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline and analogues: potent angiotensin converting enzyme inhibitors.

A new approach was developed for the synthesis of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline (1) and 23 analogues. The delta-(acylamino)-gamma-keto acid intermediates were obtained by a modified Dakin--West reaction using 3-carbomethoxypropionyl chloride. Acylation of L-proline and recrystallization of the mixture of diastereomers gave the optically pure title compound in three reaction steps. The in vitro angiotensin converting enzyme (ACE) inhibitory activity of 1 was confirmed. Some of the novel analogues (6, 11, 13, and 17) were also found to be potent inhibitors of ACE in vitro with an IC50 of 1.4-8.8 x 10(-9) M (IC50 for captopril = 0.9 x 10(-8) M). In vivo these compounds (6, 11, 17, and 18) were much less active than captopril, especially by the oral route. Against angiotensin I (AI) challenge in normotensive conscious rats, 1 and 6 produced less than 50% inhibition at 30 mg/kg po but 57 to 82% inhibition at 3 mg/kg iv. Inhibition by both routes lasted less than 1 h. In renal hypertensive rats, 1 and 15 of its analogues failed to produce significant blood pressure lowering effects, in contrast to the marked effects of captopril. Near maximum inhibition of AI was achieved by continuous intravenous infusions of 1 and 20, suggesting that limited oral activity may by due to degradation and/or clearance.

Angiotensin II↗
PubMed1981

Effects of medroxyprogesterone acetate and caloric restriction on the distribution of serum and liver lipids and proteins in female rats.

The effects of a large dose (2 mg/100 g body weight) of medroxyprogesterone acetate (MPA), restricted feeding (50% of normal intake) and their interaction were investigated on the serum and liver lipid and protein distribution in female rats. MPA increased serum cholesterol and triglyceride levels in rats on ad libitum food intake without having any effect in the animals on restricted diet. There was no statistical difference in the total serum protein or albumin levels among the groups. The serum levels of alpha and gamma globulin were significantly lower in the underfed rats. MPA increased the concentration of gamma globulin in well nourished rats but interacted with dietary restriction to further reduce the level of this protein in the undernourished animals. There was no difference in the levels of hepatic phospholipids or free cholesterol among groups, However, cholesterol ester and triglyceride levels in liver were significantly elevated in the MPA-treated group fed ad libitum. A similar increase was not found in underfed rats. This study indicates that MPA exerts significant effects on the distribution of serum and hepatic lipids and serum globulin levels and that the effects are dependent upon the nutritional status of the subject.

Alpha-Globulins↗
PubMed1981

Abnormal head circumference in learning-disabled children.

The head circumferences of 73 learning-disabled children were compared with those of a matched control population of 71 children. Macrocephaly was noted in eight learning-disabled children but in only three controls, and microcephaly was present in seven learning-disabled children but in none of the controls. Abnormal head circumferences were noted in nine learning-disabled males but in only three control males. Since this study revealed an increased prevalence of both macrocephaly and microcephaly in children with learning disabilities, future studies of such children should include accurate measurements of head circumference. It may be found that abnormal head circumference, when accompanied by other signs, can be used to identify preschool children potentially at risk for learning disabilities.

Cephalometry↗
PubMed1981

Incorporation of leucine into phospholipids of Bacteroides thetaiotaomicron.

L-[4,5-3H]- or L-[U-14C]leucine was incorporated by Bacteroides thetaiotaomicron into acid-precipitable material even when the bacteria were treated with concentrations of tetracycline high enough to prevent growth. Similar results were obtained when L-[2,3,4-3H]valine or L-[4,5-3H]isoleucine was used instead of leucine. In bacteria which had been treated with tetracycline, the acid-precipitable label was not solubilized by treatment with protease, lysozyme, or deoxyribonuclease. However, virtually all of the label was extractable with chloroform-methanol, indicating that the label had been incorporated into membrane lipids. Since L-[1-14C]leucine was not incorporated into lipids, leucine was probably decarboxylated before incorporation. When a chloroform extract from bacteria which had been labeled with both [32P]phosphate and [3H]leucine was resolved into component phospholipids by two-dimensional thin-layer chromatography, 3H was incorporated into all of the phospholipids. When these phospholipids were deacylated, the 3H from leucine was associated with released fatty acids rather than with the head groups. Thus, it appears that B. thetaiotaomicron can utilize leucine and similar amino acids not only by incorporating them into protein but also by incorporating portions of these amino acids into membrane phospholipids.

Bacteroides↗