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Biomedical subjects

R D Smith

Publications and source records attributed to R D Smith.

At least 397 records · Page 22Linked to original sources
PubMed1984

Angiotensin-converting enzyme inhibitory and antihypertensive activities of pivalopril (RHC 3659-(S)).

Pivalopril (RHC 3659-(S); (S)-N-cyclopentyl-N-(2-methyl-3-pivaloylthiopropionyl) glycine) is a new compound with a hindered sulfur group that has been compared to captopril for oral angiotensin-converting enzyme (ACE) inhibition in rats and dogs and antihypertensive activity in rats. In separate groups of conscious normotensive rats, pivalopril (0.03-1.0 mg/kg, orally [p.o.]) produced a dose-related antagonism of angiotensin I (AngI)-induced pressor effects. The ED50 for pivalopril and captopril was 0.1 mg/kg. In conscious normotensive dogs, pivalopril (incremental doses of 0.01-1.0 mg/kg, p.o.) produced a dose-related antagonism of AngI pressor effects. The ED50 was 0.17 mg/kg for pivalopril and 0.06 mg/kg for captopril. At equieffective doses the two compounds had similar durations of action. In sodium-deficient, conscious spontaneously hypertensive rats (SHR), pivalopril (1-100 mg/kg, p.o.) produced a dose-related reduction in mean arterial pressure. The potency and duration were similar to those of captopril. In the sodium-replete SHR, 5 days of oral dosing with pivalopril, 100 mg/(kg . day), decreased mean arterial pressure more effectively than captopril, 100 mg/(kg . day). No tolerance developed to the antihypertensive effect of either drug. It is concluded that pivalopril is a potent, orally effective ACE inhibitor and antihypertensive agent.

Angiotensin I↗
PubMed1984

Antihypertensive profile of the angiotensin-converting enzyme inhibitors CI-906 and CI-907.

CI-906 and CI-907, new orally active nonsulfhydryl angiotensin-converting enzyme inhibitors, were examined for antihypertensive effects in unanesthetized hypertensive rats and dogs. In two-kidney, one-clip Goldblatt hypertensive rats, single oral daily doses (0.03-30 mg/kg) produced dose-dependent decreases in blood pressure; a single 3 mg/kg oral dose lowered blood pressure to normotensive levels. In spontaneously hypertensive rats, 30 mg/(kg X day) orally administered for 5 consecutive days achieved the same blood pressure decrease as that obtained on the first day in the renal hypertensive rats. In diuretic-pretreated renal hypertensive dogs, a 10 mg/kg oral dose decreased blood pressure by 25%. No adverse side effects were observed with CI-906 and CI-907 in any of the conscious animals. These studies indicate that CI-906 and CI-907 are potent, orally active antihypertensive agents without any apparent limiting side effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Macrocephaly and minor congenital anomalies in children with learning problems.

To determine whether existing data which indicate a significant prevalence of abnormal head circumference and minor congenital anomalies in referred learning disabled populations could be replicated in a nonreferred population, 75 children enrolled in learning disabilities resource programs in an elementary school district were compared with a matched group of 73 children. Macrocephaly (occipitofrontal head circumference of 2 or more SD above the mean) was noted significantly more often in resource than in control children (12 versus 3) (p less than 0.05). Macrocephalic resource children had significantly lower achievement scores than either normocephalic resource or control children (p less than 0.05). There were no significant differences between resource and control children for mean number of anomalies per child, frequency of individual anomalies per group, or evidence of recurring anomaly patterns in the resource children. The macrocephalic resource children revealed the same prevalence of anomalies as normocephalic resource and control children, with no evidence of recurring anomaly patterns. Resource children with four or more anomalies did not differ from those with three or fewer anomalies on any psychometric parameters. Clinical, familial, radiological, and psychometric investigation of several macrocephalic resource children indicated similar patterns of learning deficits and documented evidence of familial macrocephaly but did not show any recognizable CNS abnormalities. This study confirms a significant prevalence of macrocephaly in children with learning problems. It indicates the need for further research into the prevalance and patterns of learning deficits in children with familial macrocephaly. The results add to recent concerns about the psychoeducational criteria of specific learning disabilities.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Multiple↗
PubMed1984

Diagnostic criteria for an enzyme-linked immunosorbent assay for occult heartworm disease: standardization of the test system in naturally exposed dogs.

The development of criteria for interpreting and reporting the results of an occult heartworm enzyme-linked immunosorbent assay to practitioners is described. The antigen is a saline extract of adult female Dirofilaria immitis. The cutoff absorbance A400 nm values were estimated, using 106 dogs free of infection. Any A400 nm value less than 0.526 is considered negative and values greater than or equal to 0.784 are positive. Intermediate A400 nm values are interpreted as suspect. Absorbance values for serum samples from 13 client-owned amicrofilaremic dogs revealed a bimodal distribution consistent with presumptive diagnosis based on clinical signs, which indicates that the test may be used to support a diagnosis of occult heartworm disease. The present serotest, however, is unable to distinguish microfilaremic dogs from noninfected dogs. Serum from dogs infected with other common helminths failed to crossreact with the D immitis antigen, with the exception of Dipetalonema reconditum.

Animals↗
PubMed1984

One department's experience with increasing the autopsy rate.

A strategy to increase the autopsy percentage at a university hospital included improving communications with the attending and resident staffs, promptly issuing initial diagnoses, and forwarding appropriate findings to a committee for potential revision of patient care practices. New autopsy permit forms included a list of all physicians interested in the case and a request that the next of kin could make for a summary of findings. These requests were subsequently filled by a summary letter from the pathologist to the family with a copy sent to the attending physician. In order to dispel certain misconceptions and improve attitudes among hospital personnel, a videotape emphasizing the purpose and potential value of the autopsy was made for viewing by nurses, social workers, clergy, and hospital administrators.

Attitude of Health Personnel↗
PubMed1984

Rates of diagnosis of six diseases of Holstein cows during 15-day and 21-day intervals.

The lactations of 3,172 Holstein dairy cows were divided into intervals of 15 and 21 days. The numbers of new diagnosis of metritis, cystic ovary, miscellaneous reproductive disorders, mastitis, left displaced abomasum, and milk fever in each interval were counted. The numbers of cows at risk in each interval were also counted. A cow was at risk if she was still milking, in the herd, and a diagnosis had not already been made for that condition in that lactation. A cow was also only at risk of a reproductive diagnosis if she was not pregnant. For each interval, the incidence rate of new diagnosis was calculated by dividing the number of new diagnoses by the number of cows at risk.

Abomasum↗
PubMed1983

High mobility group proteins: abundance, turnover, and relationship to transcriptionally active chromatin.

We have measured the abundance of high mobility group (HMG) proteins 14 and 17 in HeLa cell chromatin and their fractionation with respect to transcriptionally active sequences. HMG protein 17 constitutes 10-20% of the mass of an individual core histone; HMG 14 is approximately one-tenth the mass of HMG 17. The enrichment of HMG proteins, relative to bulk chromatin, is less than 2-fold in the chromatin fraction enriched 6-fold in active sequences. The digestion characteristics of HMG nucleosomes indicate that they are interspersed with H1 nucleosomes and other monomer species. The HMG monomers are quite resistant to degradation by micrococcal nuclease and can be resolved as distinct nucleoprotein entities after trimming of the DNA to core length. Turnover measurements showed that HMG proteins 14 and 17 are stable for at least 24 h. When nucleosome monomers are reconstituted with a 0.35 M NaCl nuclear protein extract, each nucleosome subtype can be reconstituted; however, this is a function of both the amount of extract added and the DNA length of the nucleosomes. When the kinetics of reconstitution of bulk vs. coding sequences were measured with cDNA, there was no significant enrichment of active sequences in the HMG-containing mononucleosomes of HeLa cells at any ratio of extract to monomer employed. In Friend cells, the abundance of sequences among mononucleosome species was the same for the transcribed beta-major globin gene, a transcriptionally inactive embryonic globin, and an inactive immunoglobulin gene. There was little correlation of HMG content with transcriptionally active chromatin, either native or reconstituted.

Chromatin↗
PubMed1983

Association of parturient hypocalcemia with eight periparturient disorders in Holstein cows.

The association between parturient hypocalcemia and 8 periparturient disorders (dystocia, retained fetal placenta, metritis, left displaced abomasum, foot problems, ketosis, mastitis, and coliform mastitis) was evaluated in 33 Holstein dairy herds (2,190 cows) that calved from March 1981 through February 1982. There were highly significant (P less than 0.0001) associations between parturient hypocalcemia and dystocia, retained fetal placenta, ketosis, and mastitis. The odds ratios (multiplicative increases in occurrence) for these associations were 6.5, 3.2, 8.9, and 8.1, respectively. There was a significantly (P less than 0.03) association between parturient paresis and coliform mastitis (odds ratio, 9.0). There was a tendency for association with left displaced abomasum (odds ratio, 3.4; P less than 0.06).

Abomasum↗
PubMed1983

Babesia bovis: computer simulation of the relationship between the tick vector, parasite, and bovine host.

Components contributing to the survival of Babesia bovis in its tick vector (Boophilus microplus) and bovine host were identified and their relationship simulated with an interactive BASIC computer program. Estimates for major independent variables (host-finding success, feeding success, filial infection rate, recovery rate) were derived from published laboratory and field data. Values for dependent variables (tick burden, inoculation rate, tick and bovine infection rates) were calculated during successive tick generations until equilibrium conditions were reached. The simulation was used to predict the effects of alternate disease control strategies. Babesiosis outbreaks were associated with simulated daily infestations of approximately two to eight engorged ticks. Below this range, B. bovis parasites disappeared, while above it all cattle were infected during the period of calfhood resistance (through 9 months of age). The babesial inoculation rate was most unstable over the above range due to instability in tick populations and tick infection rates. The risk of babesiosis outbreaks among older, less resistant cattle was also greatest over this range. The optimum daily infestation was eight to nine engorged ticks. This level would maintain herd immunity to babesiosis without causing significant physiologic stress to the bovine host. The difficulty in maintaining ecological and immunological stability at low infestation rates discourages "strategic dipping" as a means of maintaining herd immunity to babesiosis. Introduction of tick-resistant cattle provided a more effective means of reducing the risk of babesiosis outbreaks. The economic implications of computer-simulated babesiosis control alternatives should be analyzed. The validity of simulation parameters should be confirmed by field studies on the relationship between tick burdens and the babesial inoculation rate. These studies would be greatly facilitated by development of an assay system for the detection of babesiae in field-collected ticks.

Aging↗
PubMed1983

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

The effect of acylation with a variety of acids on the antihypertensive activity of 6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidine-7-amine (1) is reported, and structure-activity relationships are discussed. Although several of the compounds show good oral antihypertensive activity in the conscious, spontaneously hypertensive rat (SHR), their activity profile appears to differ from 1 in that the onset of action is shortened at comparable blood pressure lowering doses, and the magnitude of effect is considerably greater at higher doses. A variety of urea, thiourea, guanidine, and amidine analogues also were prepared. Although many of these derivatives showed some antihypertensive effects when dosed orally to SHR, this activity was weaker and of shorter duration than that obtained with 1. Aqueous solubilities and hydrolytic stabilities for four of the more active compounds were measured and suggest that these do not function as prodrugs of 1.

Animals↗
PubMed1983

Transcribed chromatin exhibits an altered nucleosomal spacing.

The nucleosomal repeat lengths of bulk chromatin and the chromatin of transcriptionally active and inactive genes were analyzed in two mouse cell lines and adult mouse spleens. The adult beta-globin gene exhibits a nucleosomal repeat length approximately 11 base pairs longer than (i) an inactive embryonic globin gene, epsilon y3; (ii) an immunoglobulin heavy chain gene, Cmu; and (iii) the bulk chromatin in murine erythroleukemia cell line DS19. The repeat length of the Cmu gene was approximately 14 base pairs longer than that of the adult beta-globin or epsilon y3 genes in the IgM-producing cell line M104E. The chromatin of several inactive genes had repeat lengths less than or equal to bulk chromatin. Individual genes were shown to vary in repeat length among the cell types examined. In addition, genes that exhibited an increased nucleosomal spacing were digested to mononucleosomes more rapidly than bulk chromatin or inactive genes with shorter repeats. Increased repeat length was also correlated with an increased sensitivity to DNase I. Thus, increased nucleosomal spacing may be a property of transcriptionally active genes or genes with the potential for transcription.

Animals↗
PubMed1983

A recombinant DNA plasmid which inhibits bacteriophage T7 reproduction in escherichia coli.

Escherichia coli plasmids carrying a DNA restriction fragment corresponding to the extreme right end of the T7 bacteriophage genome render cells incompetent to support reproduction of wild-type T7. Processing of intracellular concatemeric phage DNA and cell lysis are perturbed by one such plasmid, pRS148. The results are discussed with reference to the possibility that the right end of the T7 genome encodes a lysis-related function.

DNA Replication↗
PubMed1983

Calcium entry blockers: key issues.

Calcium entry blockers (CEBs) are of widespread interest because of the primary role of Ca2+ in excitation-contraction coupling in vascular smooth muscle and the probable involvement of Ca2+ in the etiology of hypertension. The role of CEBs in the chronic management of essential hypertension, however, has not been established. Key issues are the definition of CEB, mechanism of vasodilator action(s), tissue selectivity, quality of antihypertensive effects, other effects, and future developments. CEBs may have multiple intracellular and extracellular sites of action and may modify both energy production and excitation-contraction coupling in vascular smooth muscle. CEBs are not unique in their vasodilator-antihypertensive profile. Other effects, e.g., coronary vasodilator or cardioprotective effects, of CEBs and their tissue selectivity may, however, provide a favorable benefit/risk profile for their chronic use in essential hypertension. New CEBs may be called modifiers of calcium metabolism, may actually be curative in hypertension, and will most certainly be of major physiological and pharmacological interest.

Animals↗