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Biomedical subjects

L Rhodes

Publications and source records attributed to L Rhodes.

At least 37 records · Page 2Linked to original sources

5 alpha-Androstan-3 alpha,17 beta-diol is a hormone: stimulation of cAMP accumulation in human and dog prostate.

5 alpha-Androstan-3 alpha, 17 beta-diol (3 alpha-diol) is a well known metabolite of dihydrostestosterone (DHT) and the concentration of its glucuronide in serum is looked upon as a marker of DHT activity in skin and prostate. The data in this communication show that 3 alpha-diol is a potent agonist of the human and canine prostatic SHBG-[SHBG receptor]. It causes a robust rise in intracellular cAMP within minutes; the 1/2 max. response occurs at a concentration equal to its concentration in male plasma. Estradiol is the only other agonist in this system. All other steroids that bind to SHBG are antagonists.

Androstane-3,17-diol↗

Benefit-cost analysis of community residential versus institutional services for adults with severe mental retardation and challenging behaviors.

A benefit-cost analysis was conducted to compare services in community residences versus an institution for 11 individuals with severe mental retardation and challenging behaviors who had been moved from an institution to a community setting. Effects that were not readily quantifiable in economic terms also were examined. Overall, the community-based program costs represented slight public savings over costs of the state institution. However, community living netted significant increases in variables such as resident's social networks, opportunities for integrated activities, and income.

Activities of Daily Living↗

The role of physicians' personal knowledge of the patient in clinical practice.

BACKGROUND: Primary care physicians' personal knowledge of their established patients has not been investigated systematically, and its role in clinical practice has not been characterized empirically. METHODS: A qualitative study used an iterative, grounded theory method for thematic analysis of transcribed, semistructured long interviews. Subjects were family physicians in stable employment and in continuous clinical practice for at least 2 years at a staff-model health maintenance organization. RESULTS: Personal knowledge of the patient clearly influenced the use of time in the examination room, the recognition of changes in baseline status, and the ability to verbalize medical information in terms that have unique meaning for particular patients. Personal knowledge fostered a sense of predictability in personal interactions; facilitated the creation of trust; served as an organizing scheme for data collection, recall, and interpretation; counterbalanced impersonal professional principles such as compulsiveness, duty, and responsibility; shaped ability to communicate effectively about issues related to quality of life and functional status; influenced choices of consultants; but also had the potential to interfere with diagnosis or with patient presentation of new information. CONCLUSIONS: Personal knowledge of patients was an important influence on physicians' daily clinical practice in this setting.

Adult↗

Effect of inhibiting 5 alpha-reductase activity on the ability of testosterone to inhibit luteinizing hormone release in male sheep.

The extent to which inhibitory effects of testosterone (T) on LH secretion in the ram are mediated by its metabolite dihydrotestosterone (DHT) is unknown. Our objective was to determine the effect of inhibiting 5 alpha-reductase activity on pulsatile patterns of LH release in castrated, T-treated male sheep. Nine Dorset and six Hampshire castrated male sheep were allocated equally to one of three treatment groups: 1) infusion of T (768 micrograms/kg/day), 2) infusion of the reductase inhibitor (RI) L-651,723 (0.6 mg/kg/day), and 3) T+RI infusion. Treatments were continuously infused for 3 days. Blood samples were collected via an indwelling jugular catheter at 10-min intervals for 4 h immediately prior to (Day 0) and during the final 4 h of infusion (Day 3). Changes in mean LH, LH pulse amplitude, LH interpulse interval (IPI), T, 17 beta-estradiol (E), and DHT were derived for each animal by subtracting values for Day 0 from Day 3. Data were subjected to one-way analysis of variance. The increase in T and E after infusion of T was similar (p > 0.10) in T- and T+RI-treated males and greater (p < 0.01) than in RI-treated males. The increase of DHT was greater (p < 0.01) in T-treated than either T+RI- or RI-treated males whereas the change was similar (p > 0.10) for T+RI- and RI-treated males. T decreased mean LH more (p < 0.01) than RI. T+RI suppressed mean LH more (p < 0.01) than RI but not as much (p < 0.01) as T alone.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗

The effects of finasteride (Proscar) on hair growth, hair cycle stage, and serum testosterone and dihydrotestosterone in adult male and female stumptail macaques (Macaca arctoides).

Finasteride, a 5 alpha-reductase inhibitor, was administered orally (1 mg/kg.day) for 6 months to six male and five female stumptail macaques. Vehicle was given to five male and five female animals over the same period of time. Hair weights in a defined 1-in.2 area of frontal scalp were measured periodically every 1-2 months, and serum was collected for measurement of testosterone and dihydrotestosterone. In addition, scalp biopsies were taken before and 6 months after treatment to evaluate the micromorphometry of hair follicles. Results showed that both male and female serum dihydrotestosterone levels were significantly reduced (60-70%) by finasteride treatment. Both males and females showed statistically significant increases in mean hair weight over the treatment period compared to controls (P = 0.034). In addition, there was a statistically significant increase in mean follicle length (measured histologically in scalp biopsies) compared to baseline in the finasteride-treated animals (P = 0.028). These data show that an inhibition of 5 alpha-reductase in the stumptail macaque can reverse the balding seen with age in both the male and female animals.

Animals↗

Comparison of finasteride (Proscar), a 5 alpha reductase inhibitor, and various commercial plant extracts in in vitro and in vivo 5 alpha reductase inhibition.

Human prostate was used as a source of 5 alpha reductase. Compounds were incubated with an enzyme preparation and [3H]testosterone. [3H]-dihydrotestosterone production was measured to calculate 5 alpha reductase activity. IC50 values (ng/ml) were finasteride = 1; Permixon = 5,600; Talso = 7,000; Strogen Forte = 31,000; Prostagutt = 40,000; and Tadenan = 63,000. Bazoton and Harzol had no activity at concentrations up to 500,000 ng/ml. In castrate rats stimulated with testosterone (T) or dihydrotestosterone (DHT), finasteride, but not Permixon or Bazoton, inhibited T stimulated prostate growth, while none of the three compounds inhibited DHT stimulated growth. These results demonstrate that finasteride inhibits 5 alpha reductase, while Permixon and Bazoton have neither anti-androgen nor 5 alpha reductase inhibitory activity. In addition, in a 7 day human clinical trial, finasteride, but not Permixon or placebo, decreased serum DHT in men, further confirming the lack of 5 alpha reductase inhibition by Permixon. Finasteride and the plant extracts listed above do not inhibit the binding of DHT to the rat prostatic androgen receptor (concentrations to 100 micrograms/ml). Based on these results, it is unlikely that these plant extracts would shrink the prostate by inhibiting androgen action or 5 alpha reductase.

5-alpha Reductase Inhibitors↗

Prostaglandin receptors coupled to adenylyl cyclase in the iris-ciliary body of rabbits, cats and cows.

Stimulation of adenylyl cyclase by prostaglandin (PG) receptor agonists was examined in the iris-ciliary body of rabbits, cats and cows. Iris-ciliary bodies were incubated with or without agonists in Krebs pyruvate buffer containing protease and cyclooxygenase inhibitors. The formation of cAMP in a 15-min period in response to the agonists was measured. In the rabbit iris-ciliary body, all PG receptor agonists at concentrations of 0.062-10.0 microM with the exception of sulprostone stimulated adenylyl cyclase. In this species, 17-phenyl trinor PGE2 and PGF2 alpha stimulated adenylyl cyclase but only at high concentrations (> 5 microM). The order of potency of the agonists was dimethyl PGE2 > PGE2 > 11-deoxy PGE1 = PGD2 > iloprost > PGF2 alpha. The DP receptor antagonist BWA868C had no effect on EP agonist responses, indicating that PGE2, dimethyl PGE2 and 11-deoxy PGE1 were not stimulating DP receptors. In the cat, PGE2, dimethyl PGE2 and 11-deoxy PGE1, were all equally potent in stimulating adenylyl cyclase. The order of potency in the cow was PGE2 > dimethyl PGE2 > 11-deoxy PGE1. However, PGD2, iloprost, 17-phenyl trinor PGE2 and PGF2 alpha were inactive in this species. The results of this study indicate that EP receptor agonists stimulate adenylyl cyclase in the iris-ciliary body of the three species; stimulation by other agonists depends on the species. In the rabbit, the EP2 receptor subtype appears to predominate; such a predominance of EP2 receptors was not observed in the cat and cow.

Adenylyl Cyclases↗

Prostaglandin E2 and F2 alpha binding sites in the bovine iris ciliary body.

PURPOSE: To determine the regional distribution and selectivity of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) specific binding sites in membrane preparations from bovine iris ciliary body. METHODS: Bovine eyes were obtained fresh from a local abattoir. Whole irides were separated into sphincter muscle, ciliary body, and remaining iris tissue then homogenized in 50 mM tris buffer, pH 7.5, containing cyclooxygenase, protease, and soybean trypsin inhibitors. Membranes were obtained after three-stage high-speed centrifugation then reconstituted in buffer. Aliquot portions were incubated with 3H-PGE2 or 3H-PGF2 alpha at 37 degrees C for 30 min in a final volume of 500 microliters. Competition studies were performed in the presence of up to 1000-fold excess unlabeled ligand. At the end of a 30-min incubation period, free and membrane bound ligand were separated by rapid filtration through a type HA millipore filter preequilibrated with buffer. The radioactivity bound to the membranes retained on the filter was quantitated in a scintillation counter. RESULTS: The equilibrium dissociation constant and maximum number 3H-PGE2 saturable binding sites were determined by Scatchard analysis. The data best fit to a single binding site model for all three membrane preparations. The majority of the 3H-PGE2 specific binding sites were in sphincter muscle (65%), followed by iris (17%), and ciliary body (18%). 3H-PGE2 alpha binding sites were not measurable in either iris or ciliary body and PGF2 alpha was less competitive than PGE2 in all tissues. The rank order of potency for agonist displacement by both 3H-PGE2 and 3H-PGF2 in sphincter muscle membrane was PGE2 > PGF2 alpha > PGD2 > Iloprost. It was determined that 3H-PGE2 and 3H-PGF2 alpha binding in the bovine sphincter was primarily to EP not FP, DP, or IP prostaglandin receptor types. CONCLUSIONS: The characteristics of PGE2 and PGF2 alpha specific binding sites in the bovine sphincter correlate with its in vitro contractile response to these prostanoids. The inability of PGF2 alpha to effectively compete with PGE2 for specific binding sites in the sphincter and lack of high affinity PGF2 alpha specific binding sites in the iris and ciliary body suggests that this prostaglandin may exert its in vivo effects through PGE2 specific binding sites.

Animals↗

Prostaglandin E2 binding site distribution and subtype classification in the rabbit iris-ciliary body.

The distribution and characteristics of specific binding sites for tritium labeled prostaglandin E2 (3H-PGE2) were examined in membrane preparations from rabbit iris-sphincter, iris and ciliary body. The majority of 3H-PGE2 specific binding sites were found in the ciliary body (46%) followed by the iris (37%) and the iris-sphincter muscle (5%). Scatchard analysis of saturable 3H-PGE2 binding sites in the ciliary body indicated a single binding site with a Kd of 2.81 nM and Bmax value of 84 fmoles bound/mg protein. Competition by agonists selective for the EP1, EP2 and EP3 receptor subtypes of the EP (PGE2) prostanoid receptor indicated that the majority of rabbit ciliary body 3H-PGE2 binding sites are of the EP2 subtype. Incomplete displacement of labeled 3H-PGE2 from its binding sites by the EP2 selective agonist 11-deoxy PGE1 suggests the presence of additional EP or non-EP binding sites. There was essentially no binding to EP1 receptor sites as defined by the displacement of 3H-PGE2 by 17-phenyl-trinor PGE2. A weak displacement of 3H-PGE2 by the EP3/EP1 specific agonist, sulprostone, may account for the presence of a small number of EP3 specific binding sites in this tissue. The predominant distribution of PGE2 binding sites in the ciliary body and their identification as EP2 selective, supports recent functional studies where topical application of prostanoids with EP2 but not EP1 or EP3 agonist activity resulted in breakdown of the blood-aqueous barrier.

Animals↗

A multicentre randomized placebo-controlled double-blind study on the efficacy of Ketotifen in infants with chronic cough or wheeze.

The efficacy of Ketotifen was examined in the treatment of 113 infants between 6 and 36 months of age presenting with a history of cough and/or wheeze in a multicentre randomized placebo-controlled double-blind study. A 4 week no-medication baseline phase preceded the 16 week treatment phase in which infants took 2.5 mL twice daily of either placebo or Ketotifen (0.5 mg) syrup; this was followed by a 4 week wash-out phase. Diary card evaluation was performed by the parent or guardian for the duration of the study and recorded wheeze and cough twice daily as well as medication used. The percentage of symptom-free days decreased significantly in both groups (P < 0.005) with placebo-treated infants experiencing significantly more symptom-free days compared with the Ketotifen group (P < 0.01), although this difference was never more than 10% in any 4 week treatment period. Symptom severity scores and use of beta-agonist medication were also less in the placebo-treated infants but did not reach statistical significance. This study was unable to show a therapeutic advantage of Ketotifen over placebo in this group of infants with chronic cough and/or wheeze and the apparent statistical advantage of placebo is not a clinically relevant finding.

Child, Preschool↗

The ROX3 gene encodes an essential nuclear protein involved in CYC7 gene expression in Saccharomyces cerevisiae.

The ROX3 gene was identified during a hunt for mutants with increased expression of the heme-regulated CYC7 gene, which encodes the minor species of cytochrome c in the yeast Saccharomyces cerevisiae. The rox3 mutants caused a 10-fold increase in CYC7 expression both in the presence and absence of heme, had slightly increased anaerobic expression of the heme-activated CYC1 gene, and caused decreases in the anaerobic expression of the heme-repressed ANB1 gene and the aerobic expression of its heme-induced homolog. The wild-type ROX3 gene was cloned, and the sequence indicated that it encodes a 220-amino-acid protein. This protein is essential; deletion of the coding sequence was lethal. The coding sequence for beta-galactosidase was fused to the 3' end of the ROX3 coding sequence, and the fusion product was found to be localized in the nucleus, strongly suggesting that the wild-type protein carries out a nuclear function. Mutations in the rox3 gene showed an interesting pattern of intragenic complementation. A deletion of the 5' coding region complemented a nonsense mutation at codon 128 but could not prevent the lethality of the null mutation. These results suggest that the amino-terminal domain is required for an essential function, while the carboxy-terminal domain can be supplied in trans to achieve the wild-type expression of CYC7. Finally, RNA blots demonstrated that the ROX3 mRNA was expressed at higher levels anaerobically but was not subject to heme repression. The nuclear localization and the lack of viability of null mutants suggest that the ROX3 protein is a general regulatory factor.

Alleles↗

Chronic utero-ovarian vein catheterization with subsequent occlusion prolongs the estrous cycle and changes electromyographic activity in the myometrium of ewes.

The objective of our study was to determine the effect of chronic utero-ovarian vein catheterization in ewes on estrous cycle length, plasma progesterone (P) concentration, and myometrial electromyographic activity. Cyclic ewes with inferior vena cava catheters were used as controls. Estrus was synchronized in ten ewes and 10 to 12 d following estrus, the ewes were anesthetized, fitted with myometrial electromyograph leads and with utero-ovarian vein (n = 5) or inferior vena cava (n = 5) catheters. After surgery, ewes returned to estrus as expected (16 to 18 d interestrus interval). The second cycle of four of five ewes with utero-ovarian vein catheters were prolonged (40 to 58 d). The inferior vena cava catheterized ewes had normal length second cycles. Plasma P concentrations reflected the estrous cycles: low (</= 0.01 ng/ml) at estrus and 2 to 3 ng/ml at midcycle. The inferior vena cava catheterized ewes had decreased plasma P concentrations after luteolysis (Days 13 to 14) while four of five utero-ovarian vein catheterized ewes maintained elevated plasma P concentrations for 20 to 58 d. Catheterization affected the myometrial electromyograph; short events (16 to 180 sec) were increased on Days 5 to 13 in utero-ovarian vein as compared with inferior vena cava catheterized ewes (P < 0.05); long events (180 to 900 sec) tended to decrease from Days 1 to 15 in utero-ovarian vein ewes, but this was not statistically significant (P > 0.05).

Journal Article↗

Interleukin 2 activation of natural killer cells rapidly induces the expression and phosphorylation of the Leu-23 activation antigen.

IL-2 potentiates both growth and cytotoxic function of T lymphocytes and NK cells. Resting peripheral blood NK cells can respond directly to rIL-2, without requirement for accessory cells or cofactors, and enhanced cytotoxicity can be measured within a few hours after exposure to this lymphokine. In this study, we describe an activation antigen, Leu-23, that is rapidly induced and phosphorylated after IL-2 stimulation of NK cells and a subset of low buoyant density T lymphocytes. Previously, it has been uncertain whether all NK cells or only a subset are responsive to IL-2. Since within 18 h after exposure to IL-2, essentially all NK cells express Leu-23, these findings indicate that all peripheral blood NK cells are responsive to stimulation by IL-2. The Leu-23 antigen is a disulfide-bonded homodimer, composed of 24-kD protein subunits with two N-linked oligosaccharides. Appearance of this glycoprotein on NK cells is IL-2 dependent and closely parallels IL-2-induced cytotoxicity against NK-resistant solid tumor cell targets.

Antigens, CD↗

Comparison of a controlled internal drug release device containing progesterone with intravaginal medroxyprogesterone sponges for estrus synchronization in ewes.

Intravaginal progestagens have been used for many years to synchronize estrus in ewes. This experiment compares two such treatments: 60 mg medroxyprogesterone (MAP) sponges and a controlled internal drug release (CIDR) device containing 366 mg natural progesterone. No pregnant mare serum gonadotropin (PMSG) was used. Treatments were given to groups of 10 to 20 ewes for 14 d at various times during breeding season. Rams were introduced 1 d after treatment removal, and day of mating was recorded. Rams were removed after 3 d. Pregnancy was checked with ultrasound 60 d later. There was no diffeence in rate of marking by rams (88%) or pregnancy rate (57%) between treatments. Ewes receiving CIDR devices showed estrus earlier and with closer synchrony (P < 0.01). The CIDR device is comparable to the MAP sponge for estrus synchrony during the breeding season, and reasonable fertility can be achieved without the use of PMSG.

Journal Article↗

Characteristics of subjects experiencing relaxation and relaxation-induced anxiety.

The purpose of this study was to determine the psychological characteristics of people who show a paradoxical increase in anxiety during relaxation training. Thirty-eight subjects who reported being anxious 50% or more of the day, were divided into two groups based on their scores on the Tellegen and Atkinson absorption scale. Half of each group was given progressive muscle relaxation training; the other half a meditational procedure. Separate regression analyses for each group showed that during meditational procedure 32% of the change in heart rate and 42% of the change in a subjective response measured by changes in the position of an "anxiety lever", could be predicted by the subjects' scores on the Tellegen absorption scale, the cognitive component of the state version of the Cognitive-Somatic Anxiety Questionnaire, and other psychological tests. Similarly, 49% of the heart rate changes during progressive muscle relaxation training were predicted by these and other measures. The multiple R for anxiety lever during progressive muscle relaxation training was not significant, however. Three of 18 meditational procedure subjects and two of 20 progressive muscle relaxation subjects showed increased heart rates during relaxation training. Two of the three meditational procedure subjects also showed an increase in subjective tension as measured by the anxiety lever.

Adolescent↗