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Biomedical subjects

A Perkins

Publications and source records attributed to A Perkins.

At least 37 records · Page 2Linked to original sources
PubMed1998

Production and secretion of thioredoxin from transformed human trophoblast cells.

Thioredoxin is a redox active protein which has been implicated in reproductive processes. In this study we investigated the intracellular production and extracellular secretion of placental thioredoxin by human cytotrophoblast cell lines which were used as in-vitro model systems. Results clearly demonstrated that thioredoxin is not only synthesized by these cells but is also secreted and that while the intracellular thioredoxin is present only as a 12 kDa form, it would appear that the extracellular thioredoxin is present in two forms, a predominant 12 kDa form accompanied by a lower amount of a 10 kDa form. The observed localization and possible secretion of thioredoxin at the feto-maternal interface suggest important roles for this protein during pregnancy. Intracellular thioredoxin may be involved in the prevention of cellular damage due to oxidative stress whereas extracellular thioredoxin may act to integrate the actions of the cytokine network operating at the feto-maternal interface thereby assisting with implantation and the successful establishment of pregnancy.

Blotting, Western↗
PubMed1998

Interpreting risk-adjusted length of stay patterns for VA hospitals.

OBJECTIVES: The Veterans Health System must become more competitive with the private sector in terms of efficiency of care. Studies have shown significantly longer lengths-of-stay (LOS) in facilities operated by the Department of Veterans Affairs (VA) compared with private sector facilities. Most comparisons, however, have not controlled well for casemix differences or have involved small numbers of patients. The aims of this study were: (1) controlling for casemix, to accurately measure the degree by which average length of stay in Veterans Affairs facilities exceeds that of private sector hospitals and (2) to demonstrate a methodology with which individual VA facilities can identify clinical and demographic subgroups of patients associated with the higher length-of-stay averages. METHODS: Subjects of the study were Veterans Health System patients hospitalized during 1991-1993 and veteran respondents to the 1991 National Hospital Discharge Survey. Hospitals' mean length of stay adjusted for patients' diagnosis related groups, severity, demographics, and travel distances were measured. RESULTS: Veterans Affairs medical centers' average risk-adjusted length of stay was 36% higher (8.9 days compared with 6.5 days) than that of the private sector. For individual hospitals, relative length-of-stay efficiency typically varied by condition. Among 14 hospitals in the VA's midwest region, none were high risk-adjusted length-of-stay outliers in all conditions studied, and four were high outliers for some conditions and low outliers for others. CONCLUSIONS: Controlling for differences in patient demographic and clinical factors, Veterans Affairs medical centers consumed significantly more days of care than private sector hospitals. Veterans Affairs medical centers will be able to improve efficiency by identifying specific subgroups of patients whose clinical treatment should be examined.

Comorbidity↗
PubMed1997

The impact of complications after vascular surgery in Veterans Affairs Medical Centers.

The impact of perioperative complications on clinical outcomes and resource utilization was assessed for 8702 veterans who, during fiscal years 1991-1994, underwent vascular surgery procedures in DRGs 110 and 111, which include aortic and peripheral aneurysm repairs as well as renal artery and some peripheral vascular reconstructions. In-hospital mortality rate was 6.2% (537/8702). Mortality was 9.8% with any ICD-9-CM-coded complication vs 4.9% without (P < 0.001). Mortality was 28.9% in those with both cardiac and pulmonary complications, 11.0% with either cardiac or pulmonary complications, and 3.7% with neither cardiac nor pulmonary complications. Length of stay (LOS) was 25.8 +/- 21.9 days with any ICD-9-CM-coded complication vs 18.9 +/- 14.1 days without (P < 0.001). Further, RIS (Resource Intensity Scale), a measure of intensity of resource utilization, was greater in those with (3.01 +/- 0.81) vs without (2.76 +/- 0.70; P < 0.001) a complication. Pulmonary complications impacted LOS and RIS more adversely than cardiac. A logistic regression model of mortality indicated that increasing age [odds ratio (OR) 1.065], arrhythmia (OR 1.31), pneumonia (OR 2.52), surgical complications of the heart (OR 2.8), respiratory insufficiency (OR 4.75), stroke (OR 5.48), MI (OR 5.78), and acute renal failure (ARF, OR 9.58) were associated with increasing likelihood for death, whereas treatment in the largest, academically affiliated VAMCs (RPM 5) was associated with reduced mortality (OR 0.795). Increasing age, treatment in the largest affiliated (RPM 5) hospitals, arrhythmia, MI, CHF, any ICD-9-CM-coded complication, acute renal failure, respiratory insufficiency, pneumonia, and stroke progressively increased LOS by linear regression analysis, whereas surgical complications of the heart and postoperative death reduced LOS. Complications after vascular surgery have an adverse impact on perioperative mortality, length of stay, and utilization of resources.

Acute Kidney Injury↗
PubMed1997

Uroguanylin is expressed by enterochromaffin cells in the rat gastrointestinal tract.

BACKGROUND & AIMS: Guanylin and uroguanylin are recently discovered intestinal peptides. Identifying the type of cell that synthesizes and secretes each peptide is an important step toward defining their physiological functions. However, the site of uroguanylin expression has not been identified, and the site of guanylin expression remains controversial (some studies implicate goblet cells, whereas others implicate enterochromaffin cells). The aim of the present study was to identify cellular sites of uroguanylin expression in the rat gastrointestinal tract and resolve the guanylin localization controversy. METHODS: Polyclonal antibodies against two independent regions of the uroguanylin prohormone were raised and used to evaluate prouroguanylin expression by Western blotting and immunohistochemistry. In parallel, uroguanylin mRNA was localized by in situ hybridization. RESULTS: Uroguanylin propeptide expression is high in proximal small intestine, low in stomach and distal small intestine, and almost undetectable in large intestine. Uroguanylin-expressing cells are identified as a subpopulation of enterochromaffin cells. CONCLUSIONS: Previous results showing guanylin expression in enterochromaffin cells appear to be a consequence of antibody cross-reactivity for epitopes conserved between proguanylin and prouroguanylin. Expression of uroguanylin in enterochromaffin cells is consistent with the hypothesis that uroguanylin is secreted both apically (into the lumen) and basolaterally (into the circulation).

Animals↗
PubMed1997

An approach to diagnosing the acute sore throat.

Sore throat is a common presenting complaint. Although patients often are concerned that they may have group A beta-hemolytic streptococcal (GABHS) pharyngitis, most sore throats are not caused by this infection. A number of illnesses and conditions present as sore throat. After life-threatening conditions are excluded, efforts to identify and treat patients with GABHS pharyngitis are appropriate. Efforts should include a directed history and physical examination, looking for exudative pharyngitis with fever, adenopathy and lack of cough or other respiratory symptoms. These findings predict a positive GABHS culture rate of 50 percent or more. The rapid Streptococcus test has a high positive predictive value, but it has a lower sensitivity rate. Treatment strategies for patients with sore throat are based on epidemiologic factors, signs and symptoms, and results of laboratory tests.

Acute Disease↗
PubMed1996

Abdominal aortic aneurysm repair in Veterans Affairs medical centers.

PURPOSE: This study was performed to define outcomes after abdominal aortic aneurysm (AAA) repair in Veterans Affairs (VA) medical centers during fiscal years 1991 through 1993. METHODS: With VA patient treatment file data, patients were selected from diagnosis-related groups 110 and 111 and were then classified in a patient management category. In the categories of repair of nonruptured and ruptured AAA, mortality and postoperative complication rates were defined for patients who underwent AAA repair in VA medical centers during the 3-year study period. RESULTS: Hospital mortality rates were 4.86% (166 of 3419) after repair of nonruptured AAA and 47.0% (126 of 268) after repair of ruptured AAA (p<0.001). Of 292 deaths after AAA repair, 136 (43.2%) followed repair of ruptured AAA, even though ruptured AAA comprised only 7.3% of total AAA surgical volume. AAA repairs were performed at 116 VA medical centers, with 31.8+/-23.1 (range, 1 to 140) procedures performed at each center. Although many lower-volume centers had excellent results, centers that performed >or=32 AAA repairs tended to have lower in-hospital mortality rates after repair of nonruptured AAA than those that performed <or=31 procedures (4.2%+/-3.5% compared with 6.7%+/-7.8%;p<0.05). Poisson regression analysis revealed an inverse relationship between the volume of AAA repairs and individual hospital mortality (p=0.001) and a direct relationship between illness severity and hospital mortality (p=0.008). The proportion of ruptured AAAs treated in a hospital was also directly related to individual hospital mortality rates (p<0.005). Postoperative complications were associated with an increased hospital mortality rate (11.7% with complication compared with 6.5% without; p<0.0001) and length of stay (23.6+/-17.1 days compared with 18.0+/-12.4 days; p<0.0001). In a logistic regression model, increased mortality rates after AAA repair were associated with hospital type (adjusted odds ratio [OR]=0.6), increasing age (OR=1.1), patient management category severity score (OR=2.2), hemorrhage (OR=2.3), myocardial infarction (OR=2.6), disseminated intravascular coagulation (OR=4.7), AAA rupture (OR=6.0), postoperative shock (OR=10.7), cardiopulmonary arrest (OR=15.4), central nervous system complications (OR=16.0) and urologic complications (OR=2.4). CONCLUSIONS: Mortality rates after AAA repair in VA hospitals were comparable with those previously reported in other large series. Outcomes for veterans with AAA may improve by referring patients eligible for elective repair to VA medical centers with a greater operative volume or to lower-volume centers that have had excellent results.

Age Factors↗
PubMed1996

Endocrine correlates of partner preference behavior in rams.

We studied a unique group of rams that would not mate with estrous ewes during extensive testing for sexual behavior. The same rams courted males in preference to females in 30-min sexual preference tests and were classified as male-oriented (n = 6). We compared the following endocrine profiles: systemic steroid concentrations, the capacity of the testes to biosynthesize 17 alpha-hydroxyprogesterone and testosterone from 3H-progesterone in vitro, and the levels of brain aromatase activity (AA) in male-oriented rams vs. rams that were proven breeders and designated as female-oriented (n = 7). After the last behavioral test, sera were collected, and males in each experimental group were killed. Brains and testes were obtained for subsequent determinations of AA and measurements of steroidogenic enzyme activity. All dissections and subsequent assays were performed without knowledge of experimental group assignments. Serum concentration of testosterone (T), dihydrotestosterone (DHT), androstenedione, estrone (E1), and estradiol-17 beta (E2) were determined by RIA. AA was quantified by a 3H2O assay validated for neural tissue of the ram. We studied frontal, parietal and cingulate cortex, cerebellum, hippocampus, olfactory bulb, septum, amygdala, infundibulum-median eminence, and preoptic area (POA). Serum T, E1, and E2 concentrations of female-oriented subjects were significantly higher (p < 0.05) than those in male-oriented subjects (SEM: 1559 +/- 228, 46 +/- 2, and 15 +/- 3 pg/ml vs. 874 +/- 196, 40 +/- 2, and 8 +/- 1 pg/ml serum, respectively). DHT and androstenedione concentrations in the systemic circulation did not differ between groups. Likewise, biosynthesis of labeled T and 17 alpha-hydroxyprogesterone from 3H-progesterone by testicular homogenates in vitro was significantly higher (p < 0.05) in female-oriented than in male-oriented subjects (28.8 +/- 8.1 vs. 12.1 +/- 2.3 mumol.h-1.mg protein-1 for T and 416.9 +/- 100.8 vs. 186.3 +/- 30.7 mumol.h-1.mg protein-1 for 17 alpha-hydroxyprogesterone). The highest level of AA was found in the POA, which was significantly greater in female-oriented than in male-oriented rams (472 +/- 34 vs. 296 +/- 24 fmol 3H2O.h-1.mg protein-1, p < 0.05). AA in other brain areas did not differ between experimental groups. Our data suggest that the testes of the male-oriented ram have reduced capacity for T production. In other species, T controls in situ estrogen formation not only by providing substrate for aromatization but also by up-regulating P450arom mRNA in the POA. Because the POA is part of a neural circuitry that mediates male sexual behavior in many species, we hypothesize that the capacity for aromatization influences sexual orientation of these rams.

17-alpha-Hydroxyprogesterone↗
PubMed1996

Isolation and characterization of the cDNA encoding BKLF/TEF-2, a major CACCC-box-binding protein in erythroid cells and selected other cells.

CACCC boxes are among the critical sequences present in regulatory elements of genes expressed in erythroid cells, as well as in selected other cell types. While an erythroid cell-specific CACCC-box-binding protein, EKLF, has been shown to be required in vivo for proper expression of the adult beta-globin gene, it is dispensable for the regulation of several other globin and nonglobin erythroid cell-expressed genes. In the work described here, we searched for additional CACCC-box transcription factors that might be active in murine erythroid cells. We identified a major gel shift activity (termed BKLF), present in yolk sac and fetal liver erythroid cells, that could be distinguished from EKLF by specific antisera. Through relaxed-stringency hybridization, we obtained the cDNA encoding BKLF, a highly basic, novel zinc finger protein that is related to EKLF and other Krüppel-like members in its DNA-binding domain but unrelated elsewhere. BKLF, which is widely but not ubiquitously expressed in cell lines, is highly expressed in the midbrain region of embryonic mice and appears to correspond to the gel shift activity TEF-2, a transcriptional activator implicated in regulation of the simian virus 40 enhancer and other CACCC-box-containing regulatory elements. Because BKLF binds with high affinity and preferentially over Sp1 to many CACCC sequences of erythroid cell expressed genes, it is likely to participate in the control of many genes whose expression appears independent of the action of EKLF.

Amino Acid Sequence↗
PubMed1995

A comparison of LH secretion and brain estradiol receptors in heterosexual and homosexual rams and female sheep.

This study examined endocrine components of sexual orientation of male sheep. Sexual orientation of adult rams was identified through standardized sexual performance tests. Four rams that copulated with ewes, four rams that never mounted females and copulated with males, and eight ewes were used in the experiments. Exogenous estradiol benzoate (50 micrograms, i.m.) stimulated (P < .05) a preovulatory-like LH surge 16-22 hr after administration to females. Estradiol did not (P > .05) affect LH release of heterosexual or homosexual rams. Thirty days after the estradiol challenge, sheep were euthanized and areas of the amygdala (AMY), hypothalamus (HYP), anterior pituitary (AP), and preoptic area (POA) of the hypothalamus were collected. Occupied and unoccupied content of estradiol receptors (ER) was determined. The content of ER in the amygdala of both homosexual rams and ewes was similar, but less than (P < .05) the content of ER in heterosexual rams. The ER content measured in other brain regions did not differ by sex or orientation. In summary, results from these data show that the preovulatory LH surge mechanism that is a characteristic of the female does not occur in either homosexual or heterosexual rams. Conversely, the ER content of the AMY of homosexual rams is similar to that of ewes and differs from the heterosexual male. Differences in ER content between heterosexual and homosexual rams imply that the amygdala serves as a link for input from potential mates. These data suggest that the amygdala not only plays a role in sexual behavior but may be involved in sexual orientation of rams.

Animals↗
PubMed1994

Effect of morphine and naloxone on LH response and sexual behavior of rams (Ovis aries).

Effects of the opiate agonist, morphine, and antagonist, naloxone, on LH release, courtship behavior and ejaculation frequency of mature, sexually active or sexually inactive rams were investigated. Plasma LH concentrations were monitored from blood samples collected every 15 min for 10 hr (0800 to 1800 hr) from eight rams that were isolated from or in contact with estrous females. Plasma LH concentration was higher (P < .05) in sexually active rams exposed to receptive females compared with hormone concentration of rams isolated from ewes. Intravenous infusion of morphine sulphate (1 mg/kg) into rams 4 and 6 hr after exposure to ewes reduced (P < .05) plasma LH concentration as compared to rams given saline. Morphine did not affect (P > .05) courtship behavior (investigatory sniff, mount attempt, foreleg kick, flehmen, vocalization) but diminished (P < .05) number of ejaculations. In another trial, LH concentrations were higher (P < .05) in seven sexually active rams given naloxone iv or when given to three rams through an intracerebroventricular cannula (icv) as compared to LH response of sexually inactive rams. LH did not differ (P > .05) in seven sexually inactive rams before or after administration of naloxone. Investigatory sniffs by sexually active rams were increased (P < .03) after treatment with the opiate antagonist. Four of the seven sexually active rams had more ejaculations after naloxone compared with the pretreatment period, but mean ejaculation frequency after treatment did not differ (P = .31). Naloxone did not stimulate courtship behavior of sexually inactive males.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The behavioral component of the ram effect: the influence of ram sexual behavior on the induction of estrus in anovulatory ewes.

The objective of this study was to test whether the sexual behavior of the ram affects the ram effect. Rams exhibiting either high (HP) or low (LP) levels of sexual performance (on the basis of serving capacity tests) were exposed to 89 anestrous ewes for 28 d. Thirty-two anestrous ewes were not exposed to rams. The objective of this study was to compare the efficacy of estrus induction by HP (n = 4) vs LP (n = 4) rams. Plasma progesterone concentration was used as an index of ovarian activity. Groups of ewes were exposed to either an HP or an LP ram in a .32-ha pasture. Courtship behaviors of rams were recorded for 6 h on the initial day of exposure and for 30-min periods on alternate days thereafter. A greater percentage of ewes exposed to HP rams ovulated (95%) compared with ewes exposed to LP rams (78%) (P < .02). On the 1st d of exposure, the HP rams exhibited more courtship behavior and spent more time near the ewes (P < .04). The HP rams spent more time within 1 m of ewes during the 28-d exposure. There were no differences in the amount of contact with rams (LP or HP) between rise in progesterone indicate of ovulation tended to occur earlier (P = .06) in ewes penned with HP rams. A greater percentage of ewes exposed to LP rams (P = .03) had early elevations of progesterone with no concurrent sexual behavior. These data imply that in addition to a pheromone the sexual behavior of the ram may be important in initiating ovarian cycle activity.

Anestrus↗
PubMed1993

Site-directed mutagenesis of human thioredoxin. Identification of cysteine 74 as critical to its function in the "early pregnancy factor" system.

Thioredoxin has been identified as a key component of the "early pregnancy factor" system, a system of components present in pregnancy sera which expresses a lymphocyte modifying activity in an assay known as the rosette inhibition assay. Although thioredoxin alone is inactive, addition of thioredoxin to lymphocytes in combination with nonpregnancy sera or platelet-activating factor results in a positive response. We have changed several amino acids of human thioredoxin by site-directed mutagenesis to investigate the residues required for this cooperative function. Conversion of the two active site residues (cysteines 32 and 35) to serines results in a protein devoid of classical redox activity; however, this protein retained its ability to cooperate with non-pregnancy sera or platelet-activating factor in the rosette inhibition assay. Vertebrate thioredoxins contain an additional conserved pair of cysteine residues in the C-terminal portion of the protein. Changing both to serines resulted in no change in redox activity but completely abolished function in the rosette inhibition assay. Further study revealed this function was solely dependent on cysteine 74 as conversion of only cysteine 74 to serine abolished function, whereas replacement of only cysteine 70 with serine had no effect. The nonfunctional mutants counteracted the action of pregnancy serum in the assay strongly supporting the hypothesis that thioredoxin is an integral part of the early pregnancy factor system with residue cysteine 74 having an important role.

Amino Acid Sequence↗
PubMed1993

Hypothalamic and hypophyseal receptors for estradiol in high and low sexually performing rams.

Rams, characterized over a 3-year period as being high (n = 8) or low (n = 10) sexual performers, were euthanized to determine if differences in sexual behavior were associated with differences in hypophyseal and hypothalamic receptors for estradiol. Rams were exposed to estrous ewes and courtship behavior was recorded for 5 hr prior to tissue collection. Blood samples for determination of serum concentrations of luteinizing hormone (LH) were collected every 15 min during the behavior testing period. Hourly blood samples were analyzed for serum concentrations of estradiol (E) and testosterone (T). Rams characterized as high (HP) or low (LP) sexual performers had similar LH profiles; there were no differences noted in basal concentration, number of pulses, or pulse amplitude of LH. There were no differences in serum concentrations of T or E during the behavior testing period between HP and LP rams. Unoccupied receptors for E (moles E bound x 10(-15)) in the stalk-median eminence (SME) (P < 0.05) in HP rams (15.1 +/- 3.1) were greater than those in LP rams (4.6 +/- 1.9). Occupied receptors for E (moles E bound x 10(-15)) in the preoptic area (POA) (P < 0.1) in HP rams (6.0 +/- 0.8) tended to be greater than those in the LP rams (3.8 +/- 0.8). The proportion of total E receptors (occupied+unoccupied) in the POA that were occupied was greater (P < 0.05; 0.41 +/- 0.03 vs 0.23 +/- 0.04) for HP than for LP rams. In contrast, HP rams had less (P < 0.05) occupied E receptors (moles E bound x 10(-15)) in the anterior pituitary gland (AP) than LP rams (152.0 +/- 38.5 vs 337.3 +/- 51.7). The proportion (%) of E receptors that were occupied in the AP in HP rams also tended to be less (P < 0.06) than that in LP rams (8 +/- 2 vs 14 +/- 1). No differences were detected in occupied or unoccupied E receptors in the medial basal hypothalamus, medial amygdala, or stalk-median eminence. In conclusion, differences in occupied receptors for E in the POA and the AP, and unoccupied receptors for E in the SME, were associated with differences in ram sexual behavior.

Amygdala↗
PubMed1993

A comparison of after-hours telephone calls concerning ambulatory and nursing home patients.

BACKGROUND: This study documents the frequency and nature of after-hours telephone calls to a university-based family practice, with special attention to those calls from or about nursing home patients. METHODS: All after-hours telephone calls to a free-standing family practice training program that were made during the 6 months between July 1991 and January 1992 were recorded and classified. RESULTS: Of the 821 calls recorded, 81 included telephone calls from nursing home patients. Nursing home patients, who constitute about 1% of the practice, were responsible for 10% of the calls (P < .001). Nursing home patient calls were more likely to occur on weekends (P = .013) and were more likely to be for physician notification purposes (P < .001). CONCLUSIONS: Nursing home patients generate a disproportionately large number of after-hours calls. These calls are more likely to occur on weekends and less likely to require physician action. This is a considerable hidden practice burden that needs to be taken into account when planning practice coverage.

Alabama↗