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Biomedical subjects

R F Smith

Publications and source records attributed to R F Smith.

At least 73 records · Page 4Linked to original sources
PubMed1995

Behavioral and developmental changes associated with prenatal opiate receptor blockade.

Pregnant Long-Evans hooded rats were dosed with 1, 5, or 10 mg/kg per day naloxone from gestational day 7 (GD7) through GD20. The control groups included both uninjected animals and injected animals pairfed to the 10-mg dose animals. At birth, all litters were culled to four males and four females, and fostered to undosed surrogate dams. Prenatal naloxone exposure produced changes in body weight development, pain sensitivity, and motor behavior in the offspring. Five and 10 mg/kg naloxone increased adult body weights in females only, as did the pairfeeding condition. The 10 mg/kg naloxone altered pain sensitivity (in males only) as measured by the tail flick test. Animals in the 1 mg/kg dose condition habituated more rapidly than uninjected (UN) subjects in the open field, and showed less activity than UNs as they matured. Bar pressing rates were reduced in the 10 mg/kg dose males in a visual discrimination task, while 10 mg/kg males and females showed reduced bar pressing rates on differential reinforcement of low rates of responding (DRL). These findings confirm that prenatal exposure to naloxone alters some aspects of neurobehavioral development in the rat, and are consistent with the hypothesis that 1 mg/kg prenatally may increase opiate function in offspring, while 10 mg/kg prenatally may decrease opiate functioning in the offspring.

Animals↗
PubMed1995

Identification of new members of a carbohydrate kinase-encoding gene family.

In a sequence database search using the human glycerol kinase-encoding sequence (HUMGLYKINB) as a query, we identified six previously unidentified carbohydrate kinase sequences. Five of the six newly identified sequences appear to be known types of carbohydrate kinases, four are glycerol kinases and one is a gluconokinase. The sixth newly identified sequence, the Caenorhabditis elegans gene, CER08D7.7-CEF59B2.1, shows similarity to the family of carbohydrate kinases including other glycerol kinases, xylulokinases, gluconokinases, ribulokinases, rhamnulokinases, and fucokinases. A phylogenetic comparison of this newly identified Caenorhabditis elegans gene with the other members of the carbohydrate kinase family demonstrated that this sequence cannot be assigned to one of the known classes of carbohydrate kinases.

Amino Acid Sequence↗
PubMed1995

BEAUTY: an enhanced BLAST-based search tool that integrates multiple biological information resources into sequence similarity search results.

BEAUTY (BLAST enhanced alignment utility) is an enhanced version of the NCBI's BLAST data base search tool that facilitates identification of the functions of matched sequences. We have created new data bases of conserved regions and functional domains for protein sequences in NCBI's Entrez data base, and BEAUTY allows this information to be incorporated directly into BLAST search results. A Conserved Regions Data Base, containing the locations of conserved regions within Entrez protein sequences, was constructed by (1) clustering the entire data base into families, (2) aligning each family using our PIMA multiple sequence alignment program, and (3) scanning the multiple alignments to locate the conserved regions within each aligned sequence. A separate Annotated Domains Data Base was constructed by extracting the locations of all annotated domains and sites from sequences represented in the Entrez, PROSITE, BLOCKS, and PRINTS data bases. BEAUTY performs a BLAST search of those Entrez sequences with conserved regions and/or annotated domains. BEAUTY then uses the information from the Conserved Regions and Annotated Domains data bases to generate, for each matched sequence, a schematic display that allows one to directly compare the relative locations of (1) the conserved regions, (2) annotated domains and sites, and (3) the locally aligned regions matched in the BLAST search. In addition, BEAUTY search results include World-Wide Web hypertext links to a number of external data bases that provide a variety of additional types of information on the function of matched sequences. This convenient integration of protein families, conserved regions, annotated domains, alignment displays, and World-Wide Web resources greatly enhances the biological informativeness of sequence similarity searches. BEAUTY searches can be performed remotely on our system using the "BCM Search Launcher" World-Wide Web pages (URL is < http:/ /gc.bcm.tmc.edu:8088/ search-launcher/launcher.html > ).

Amino Acid Sequence↗
PubMed1995

Stress and reproduction in farm animals.

Transport of post-partum cows or sheep before an oestradiol-induced LH surge delayed gonadotrophin secretion possibly by affecting hypothalamic activity but not via an opioid mediated mechanism as the effect could not be reversed by naloxone. In addition, reduced LH responses to GnRH were observed in cattle during transport. In sheep, adrenocorticotrophic hormone (ACTH) also diminished the LH response to GnRH, but only when GnRH was administered 3 h after ACTH, not after 0.5 h. This finding suggests that very early suppression of LH secretion by stressors is not mediated by ACTH action at the pituitary but that immediate activation of the sympathetic nervous system may be involved. In ewes during the breeding season, repeated exposure to GnRH at intervals of 2 h during transport resulted in lower LH responses to the second and third injections. When anoestrous ewes were treated with oestradiol and GnRH while being restrained and isolated, the onset of the LH surge was delayed. The effects of hypothalamus-pituitary-adrenal hyperactivity on LH release may involve suppression of GnRH receptor activity, a reduction in releasable LH, or both factors. Studies in vitro with perifused ovine pituitaries showed that ACTH or corticotrophin releasing hormone markedly suppressed LH secretion in response to the second of two exposures to GnRH. This occurred with pituitaries obtained from anoestrous ewes irrespective of prior treatment with oestradiol, suggesting that compounds from the hypothalamus-pituitary-adrenal do not exert effects on the oestradiol-sensitizing mechanisms on the pituitary. In conclusion, stressors affect reproductive function via actions at the hypothalamus as well as impairing pituitary LH release induced by GnRH.

Adrenal Glands↗
PubMed1995

Aspiration of free blood from the peritoneal cavity does not mandate immediate laparotomy.

The objective was to establish the relationship between the aspiration of free blood (+ASP) versus diagnostic peritoneal lavage (DPL), abdominal injury severity, hemodynamic instability, and the need for immediate operative intervention. We prospectively compared the significance of +ASP to +DPL in our level I trauma center. Consecutive patients received sequential needle tap, catheter aspiration (ASP), and DPL. If gross blood was withdrawn during the tap or ASP, it was returned to the peritoneal cavity before completing the DPL. The DPL was considered positive if there were > 100,000 RBCs for blunt injuries or anterior abdominal stab wounds, or > 10,000 RBCs for other penetrating injuries. During a 12-month period, 566 patients fulfilled the study criteria; they were 50 per cent blunt and 50 per cent penetrating trauma. There were 70 patients with both +ASP/+DPL, 30 with -ASP/+DPL and 4 with +ASP but -DPL. Exploratory laparotomy was performed on these 104 patients (18.4%), 22 of which were considered nontherapeutic. The ATI was statistically higher in the +ASP patients (14.9 +/- 12.9 versus 8.5 +/- 8.2, P < 0.05) but was not clinically different. Overall injury severity and hemodynamic stability were not different in the two groups. The sensitivity of DPL at detecting intra-abdominal injury was higher than the ASP group (98% versus 72%), but the specificities were equal (98%). Because +ASP patients are not more critically injured or unstable than +DPL patients, and because DPL is more accurate in detecting the need for operative intervention, aspiration should be abandoned as part of the DPL procedure in patients with abdominal trauma.

Abdominal Injuries↗
PubMed1994

Acute aortic occlusion. A 40-year experience.

OBJECTIVE: To review a large experience with acute aortic occlusion (AAO) to better define the cause, clinical presentation, treatment, prognostic variables, and outcome. DESIGN: Retrospective review of 46 consecutive patients with AAO during a 40-year period. SETTING: A large urban tertiary care referral center in Detroit, Mich. PATIENTS: Adult patients with arteriographic and/or operative confirmation of acute occlusion of the abdominal aorta plus signs and symptoms of acute ischemia. INTERVENTION: Operative and nonoperative treatment of AAO. MAIN OUTCOME MEASURES: Mortality, morbidity, and long-term survival. Other variables measured included cause, risk factors, and effects of duration and severity of ischemia and treatment methods on outcome. RESULTS: Two primary causes were identified--embolism (65%) and thrombosis (35%). Heart disease and female gender were risk factors for embolism, while smoking and diabetes were risk factors for thrombosis. Severity of ischemia on presentation correlated better with outcome than duration of ischemia. The hospital mortality rate was 35% and morbidity, 74%, with no difference between the two groups. Recurrent arterial embolism occurred in 43% of patients with embolic AAO. Seventy-two percent of AAO survivors were alive 5 years after therapy. CONCLUSIONS: Acute aortic occlusion remains a serious vascular surgical emergency with significant morbidity and mortality, even when recognized promptly and treated appropriately. Nevertheless, survivors have a reasonable long-term outcome. Permanent anticoagulation is suggested in patients with embolic AAO to minimize a high incidence of recurrent arterial embolism.

Acute Disease↗
PubMed1994

Behavioral sensitivity of rats to extremely-low-frequency magnetic fields.

Work in our laboratory has revealed autonomic and/or behavioral sensitivity of mice, rats, and a domestic fowl to extremely-low-frequency (ELF) or nominally static magnetic (B) fields at flux densities between 250 and 1700 microT (rms). To extend our work, an automated exposure and data-acquisition system was used with the technique of conditional suppression to assess behavioral sensitivity to time-varying B fields. Each of five rats was exposed aperiodically to a B field during 3 min warning periods that terminated in a brief electric shock. The difference between rates of lever pressing during B-field warning periods and rates during immediately antecedent, 3 min control periods was analyzed at frequencies of 7, 16, 30, 60, and 65.1 Hz. To produce equivalent induced voltages in the rat at each frequency, graded flux densities were established that ranged from 1900 microT at 7 Hz to 200 microT at 65.1 Hz. Analysis of differences in lever-pressing rates revealed that in a given session of testing the rats would increasingly suppress responding when exposed to a B field, but this trend was independent of frequency. This experiment provides evidence of behavioral sensitivity by a mammal to an ELF magnetic field.

Analysis of Variance↗
PubMed1994

Turbine flow sensor for volume-flow rate verification in MR.

A turbine flow sensor for MR flow experiments has been evaluated using reference volume-flow rate measurements obtained using an electromagnetic (EM) flow meter measurements and simultaneous phase contrast (PC) MR acquisitions. After calibration, the device was found to have accuracy (compared with the EM flow meter), linearity, and precision of better than +/- 1%, +/- 3.5%, 3.5%, respectively, in constant flow mode (0 to 30 ml s-1). The frequency response of the flow sensor was flat (within +/- 10%) up to 13.9 Hz. Volume-flow rate measurements on constant and simulated physiologic flow waveforms were in close agreement with both the electromagnetic (EM) flow meter and the gated MR PC estimates.

Calibration↗
PubMed1994

Mutational trends in V3 loop protein sequences observed in different genetic lineages of human immunodeficiency virus type 1.

Highly variable international human immunodeficiency virus type 1 envelope sequences can be assigned to six major clades, or phylogenetically defined subtypes, designated A through F. These subtypes are approximately equidistant in terms of evolutionary distance measured by nucleotide sequences. This radiation from a common ancestral sequence may have been in step with the spread of the pandemic. In this study, V3 loop protein sequence relationships within these major clades are analyzed to determine how the different lineages might be evolving with respect to this biologically important domain. The V3 loop has been shown to influence viral phenotype and to elicit both humoral and cellular immune responses. To identify patterns in V3 loop amino acid evolution, we cluster the sequences by a phenetic principle which evaluates protein similarities on the basis of amino acid identities and similarities irrespective of evolutionary relationships. When phenetic clustering patterns are superimposed upon phylogenetic subtype classifications, two interesting mutational trends are revealed. First, a set of identical, or highly similar, V3 loop protein sequences can be identified within two otherwise dissimilar genetic subtypes, A and C. Second, the D subtype sequences are found to possess the most radically divergent set of V3 loop sequences. These and other patterns characteristic of the V3 loop reflect the acquisition of specific biological properties during the apparently recent evolution of the human immunodeficiency virus type 1 lineages.

Amino Acid Sequence↗
PubMed1994

Further comments on the measurement of carotid stenosis from angiograms. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group.

BACKGROUND AND PURPOSE: Three different methods for estimating the percentage of reduction in the diameter of the internal carotid artery (ie, stenosis) have been proposed in the literature. Further comparisons of the methods were carried out with the intent of recommending a current standard for determining the percentage of stenosis from angiograms. METHODS: Angiograms from 112 patients were obtained. For each angiogram, stenosis was estimated in the manner of the European Carotid Surgery Trial (ECST method), the North American Symptomatic Carotid Endarterectomy Trial (NASCET method), and by a method using the common carotid artery lumen diameter (CC method). RESULTS: Although there is much discrepancy among the estimates of stenosis arising from the three different methods for any particular patient, it is possible to predict (on average) the percentage of stenosis from one method to another. The relationship between the NASCET and CC methods is linear, with a mean ratio of distal internal carotid artery to common carotid diameter of 0.62 (SD of 0.11). The variability in the diameter of the common carotid artery lumen stabilizes only beyond 2.5 common carotid diameter units (approximately 20 to 30 mm by conventional angiography) proximal to the bifurcation. Unexpectedly, the relationships between both the ECST and NASCET methods and ECST and CC methods were parabolic (P < .001). The reasons underlying these departures from linearity are uncertain. CONCLUSIONS: The comparability of our results with those reported in the literature regarding the CC and NASCET methods provides further evidence of the reproducibility of methods measuring anatomic features that can be visualized on an angiogram. Disease of the internal carotid artery is one of the important causes of ischemic symptoms. Measuring the narrowest portion of the internal artery relative to the normal portion of the same artery, well beyond the bulb, is a logical method. Moreover, benefits of carotid endarterectomy for patients with 70% to 99% stenosis as determined by the NASCET method have been well established in a clinical trial. Converting from the NASCET method to the CC method, given that the CC method is neither superior nor easier to calculate, is not recommended.

Angiography↗
PubMed1994

Opioids and suckling in relation to inhibition of oestradiol-induced LH secretion in postpartum ewes.

The effects of time postpartum and suckling status on the oestradiol-induced LH surge in ewes and some of the possible mechanisms involved were investigated. Lambs were removed from nonsuckled ewes at parturition (day 0) and the ewes hand-milked 12 and 48 h later to prevent discomfort. Nonsuckled ewes on day 1, 7, 14 or 28, and suckled ewes on day 7 or 28 postpartum were injected i.m. with 50 micrograms oestradiol benzoate (hour 0). A further eight suckled ewes were given oestradiol on day 1 (as above), and four were also given naloxone (1 mg kg-1 h-1) from 10 until 14 h after administration of oestradiol benzoate. There was no LH surge in response to oestradiol on day 1. In nonsuckled ewes the onset of the LH surge was significantly (P < 0.05) delayed when oestradiol was administered on day 7 (17.4 +/- 1.5 h), compared with when it was injected on days 14 and 28 postpartum (14.4 +/- 1.7 and 14.0 +/- 1.4 h). The LH surge was also delayed (P < 0.05) when oestradiol was administered on day 7 (18.0 +/- 2.8 h) in suckled ewes. There was no difference in the duration or amplitude of the LH surge with time postpartum in nonsuckled ewes. Suckling significantly (P < 0.05) reduced the amplitude of the LH surge on both day 7 (21.0 +/- 2.4 versus 26.4 +/- 2.3 ng ml-1) and day 28 (23.6 +/- 3.2 versus 28.8 +/- 2.9 ng ml-1), but had no effect on the onset or duration of the surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Transport stress delays the oestradiol-induced LH surge by a non-opioidergic mechanism in the early postpartum ewe.

The present study was designed to investigate whether transport, a mild environmental stressor, could affect the oestradiol-induced LH surge in postpartum ewes and, if so, the mechanism involved. Welsh Mountain ewes, with lambs removed at parturition (day 0) and hand-milked 12 and 48 h later, were given 50 micrograms oestradiol benzoate intramuscularly at various times postpartum. Blood samples were taken via an indwelling jugular venous catheter every 2 h from 8 to 24 h after oestradiol injection. All results are given as means +/- S.D. On day 1 oestradiol was unable to induce an LH surge in any ewe. Transport (10-14 h after oestradiol) delayed the onset of the oestradiol-induced LH surge on day 14 (17.5 +/- 1.7 vs 14.4 +/- 2.0 h, n = 5 each; P < 0.05), but not on day 28 (14.9 +/- 2.0 vs 14.0 +/- 2.4 h, n = 5 out of 7). Transport had no effect on the amplitude of the surge on either day. Naloxone treatment (1 mg/kg per 2 h) was unable to prevent the delay caused by transport (18.0 +/- 1.1 vs 17.5 +/- 1.7 h, n = 8 each), and did not affect the amplitude of the surge (28.4 +/- 5.3 vs 28.1 +/- 2.3 ng/ml, n = 8 each).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Repair of pararenal abdominal aortic aneurysms. An analysis of operative management.

OBJECTIVE: To analyze different operative approaches for repair of pararenal abdominal aortic aneurysm, to define factors associated with perioperative morbidity, particularly renal insufficiency, and to compare the results of pararenal abdominal aortic aneurysm repair with standard infrarenal repair. DESIGN: Case series review of all patients undergoing repair of nonruptured pararenal abdominal aortic aneurysms over 7 consecutive years at a tertiary care teaching hospital. PATIENTS: Fifty-three consecutive patients with nonruptured atherosclerotic pararenal abdominal aortic aneurysms undergoing operative repair. A comparison group of 65 patients randomly selected from a pool of 384 patients undergoing concurrent infrarenal abdominal aortic aneurysm repair. MAIN OUTCOME MEASURES: Operative morbidity and mortality, postoperative renal insufficiency, estimated blood loss, perioperative blood and fluid requirements, and length of hospital stay. RESULTS: Postoperative renal insufficiency was more likely when concomitant renal revascularization was performed (P = .007) or when any major intraoperative complication occurred (P = .008). Retroperitoneal abdominal aortic aneurysm repair was associated with lower estimated blood loss (P = .05) and less fluid requirement within the first 24 hours following operation than transperitoneal repair (P = .03). No differences in outcome measures were identified with regard to site of proximal aortic clamping (supraceliac vs suprarenal). Pararenal abdominal aortic aneurysms were larger and their repair was associated with greater estimated blood loss (P = .007), intraoperative blood replacement (P < .001), and a longer hospital stay (P = .02) than infrarenal abdominal aortic aneurysms. CONCLUSIONS: Pararenal abdominal aortic aneurysm repair is a technically challenging operation associated with significant morbidity. A retroperitoneal approach facilitates repair. The site of proximal aortic cross-clamping should be dictated by technical factors and not by any perceived outcome advantages.

Acute Kidney Injury↗
PubMed1993

Neoadjuvant cisplatin, methotrexate and vinblastine for muscle-invasive bladder cancer: long-term followup.

A total of 26 patients with locally advanced bladder cancer received chemotherapy consisting of cisplatin, methotrexate and vinblastine. Radical cystectomy was performed in 24 of 26 patients (92%) receiving neoadjuvant therapy, with a pathological complete response in 6 (23%) and pathological partial response in 1 (4%) for an overall response rate of 35% (95% confidence limits 17 to 56%). The overall median survival time is currently undefined. Of the patients 15 (58%) are alive with a median followup of 48.6 months. Response rates from this neoadjuvant chemotherapy appear to be similar to those reported with methotrexate, vinblastine, doxorubicin and cisplatin, and may represent a therapeutically equivalent regimen but neither may be curative in the majority of the patients.

Adult↗
PubMed1993

Functional capacity in heart failure. Comparison of methods for assessment and their relation to other indexes of heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Left ventricular (LV) dysfunction plays a primary role in the pathogenesis of congestive heart failure and correlates with prognosis, but a strong quantitative relation between exercise performance and indexes of LV function has not been demonstrated. We examined the relation between LV ejection fraction at rest, oxygen consumption at peak exercise (VO2), patient and physician assessments of clinical severity, and other clinical attributes in 804 patients with moderate heart failure. METHODS AND RESULTS: Ejection fraction correlated weakly with VO2, and mean ejection fraction was related to severity of symptoms. There was a statistical association between the patient's self-assessed quality of life questionnaire score and the physician-assigned New York Heart Association (NYHA) functional class; NYHA class was statistically associated with exercise performance. To identify other factors that might influence exercise capacity, comparisons of clinical attributes were made between patients grouped by VO2 within each stratum of LV function. Exercise performance was inversely related to plasma norepinephrine levels within the ejection fraction < 25% stratum. The percentage of patients reaching their anaerobic threshold was not different between groups, yet the peak heart rate increased with VO2 within all strata. Elevated venous pressure and cardiomegaly were inversely related to exercise performance. CONCLUSIONS: Clinical scales based on physician and patient assessment of symptoms were statistically associated with exercise capacity but do not accurately predict individual exercise performance. The strong association of heart rate response to exercise performance suggests that the variability of the chronotropic response to exercise contributes to differences in exercise capacity among patients with a similar degree of LV dysfunction.

Drug Therapy, Combination↗
PubMed1992

Transmission-blocking antibodies recognize microfilarial chitinase in brugian lymphatic filariasis.

Brugia malayi is a parasitic nematode that causes lymphatic filariasis in humans. The monoclonal antibody MF1, which mediates clearance of peripheral microfilaremia in a gerbil infection model, recognizes two stage-specific proteins, p70 and p75, in B. malayi microfilariae. cDNA coding for the MF1 antigen was sequenced, and the predicted protein sequence shows significant similarities to chitinases from bacteria and yeast. When microfilarial extracts and purified preparations of the MF1 antigen were tested for chitinase activity, strong bands of chitin-degrading activity comigrated in SDS/PAGE with p70 and p75 and showed a reduction-dependent mobility shift characteristic of the MF1 antigen. Thus, the MF1 antigen is microfilarial chitinase, which may function to degrade chitin-containing structures in the microfilaria or in its mosquito vector during parasite development and transmission.

Amino Acid Sequence↗