Organic movement reveals a shift in the social position of science.
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Agriculture↗
Biomedical subjects
J R Porter
Publications and source records attributed to J R Porter.
Enantioselective synthesis of arylamines through Zr-catalyzed addition of dialkylzincs to imines. Reaction development by screening of parallel libraries.
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Amines↗
A sixteen-channel multiplexing upgrade for single channel receivers.
With the increasing interest in phased arrays in magnetic resonance imaging, imaging system receivers capable of acquiring larger number of parallel signals are needed. Suggested techniques for rapid imaging propose the use of arrays with as many as 128 elements. While simply duplicating the number of receiver chains as needed is a viable technique, it quickly becomes both cumbersome and expensive. Time domain multiplexing offers an alternative solution to this problem. By using RF multiplexing switches, a single receiver can be upgraded to an array receiver capable of multi-channel data acquisition giving users array capability. Additionally, it can be used to dramatically increase acquisition capability of multiple receiver systems. This paper reports results from a multiplexing system upgrade, which converts a single channel standard clinical imaging system to a 16-channel array system. The upgrade includes both the RF multiplexing front-end and an external data acquisition system with image processing capability. Issues concerning the implementation of high channel-count multiplexers are also discussed.
Equipment Design↗
Effects of dehydroepiandrosterone and quinapril on nephropathy in obese Zucker rats.
BACKGROUND: The obese Zucker rat exhibits insulin resistance, develops nephropathy at an early age, and may be a model of diabetic nephropathy. Dehydroepiandrosterone (DHEA) may ameliorate many of the factors that contribute to diabetic nephropathy, while angiotensin-converting enzyme inhibitors are known to be effective. One marker of nephropathy is the expression of alpha-smooth muscle actin. METHODS: We studied the effect of DHEA on the expression of alpha-smooth muscle actin in obese Zucker rats and compared the changes with those in a control group, a group given quinapril, and a group on a low-calorie diet. DHEA (0.6%) added to plain chow, quinapril (0.3 mg/kg) added to drinking water, and a low-calorie diet based on pair-feeding were administered to obese rats from age 4 to 20 weeks. Immunohistochemical expression of alpha-smooth muscle actin, a marker of interstitial and glomerular fibrosis and an early indicator of nephropathy, was measured semiquantitatively in glomeruli, cortical interstitium, and medullary interstitium on a scale of 0 to 4 and was reported as mean +/- SEM. RESULTS: When compared with the obese control group, quinapril exhibited a marked reduction in alpha-smooth muscle actin staining in glomeruli, cortical interstitium, and medullary interstitium (P < 0.0005); DHEA reduced alpha-smooth muscle actin staining in cortical interstitium and medullary interstitium (P < 0. 005), and a low-calorie diet reduced alpha-smooth muscle actin staining in cortical and medullary interstitium (P < 0.005), which was similar to the effects of DHEA. CONCLUSIONS: DHEA was similar to a low-calorie diet in reducing the immunohistochemical staining of alpha-smooth muscle actin in obese Zucker rats. However, quinapril exerted a marked protective effect on the development of fibrosis, as indicated by alpha-smooth muscle actin staining, which was significantly less than that of DHEA at the doses studied.
Actins↗
Dehydroepiandrosterone alters Zucker rat soleus and cardiac muscle lipid profiles.
High levels of serum free fatty acids (FFA) and lower proportions of polyunsaturated (PU) FAs, specifically arachidonic acid (AA), are common in obesity, insulin resistance (IR), and type 2 diabetes mellitus. Dehydrepiandrosterone (DHEA) decreases body fat content, dietary fat consumption, and insulin levels in obese Zucker rats (ZR), a genetic model of human youth onset obesity and type 2 diabetes. This study was conducted to investigate DHEA's effects on lean and obese ZR serum FFA levels and total lipid (TL) FA profiles in heart and soleus muscle. We postulated that DHEA alters serum FFA levels and tissue TL FA profiles of obese ZR so that they resemble the levels and profiles of lean ZR. If so, DHEA may directly or indirectly alter tissue lipids, FFA flux, and perhaps lower IR in obese ZR. Lean and obese male ZR were divided into six groups with 10 animals in each: obese ad libitum control, obese pair-fed, obese DHEA, lean ad libitum control, lean pair-fed, and lean DHEA. All animals had ad libitum access to a diet whose calories were 50% fat, 30% carbohydrate, and 20% protein. Only the diets of the DHEA treatment groups were supplemented with 0.6% DHEA. Pair-fed groups were given the average number of calories per day consumed by their corresponding DHEA group, and ad libitum groups had 24-h access to the DHEA-free diet. Serum FFA levels and heart and soleus TL FA profiles were measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared to lean (approximately 0.6 mmol/L) ZR, regardless of group. In hearts, monounsaturated (MU) FA were greater and PU FA were proportionally lower in obese compared to the lean rats. In soleus, saturated and MU FA were greater and PU FA were proportionally lower in the obese compared to the lean rats. DHEA groups displayed significantly increased proportions of TL AA and decreased oleic acid in both muscle types. Mechanisms by which DHEA alters TL FA profiles are a reflection of changes occurring within specific lipid fractions such as FFA, phospholipid, and triglyceride. This study provides initial insights into DHEA's lipid altering effects.
Adjuvants, Immunologic↗
Discovery and evaluation of potent, cysteine-based alpha4beta1 integrin antagonists.
Acyclic, disulphide derivatives of cysteine have been identified as moderately potent antagonists of alpha4beta1-mediated leukocyte cell adhesion to VCAM. This communication describes how they were discovered from a simple L-cystine derivative and using the structure-activity data of C*DThioPC* related cyclic peptides.
Cysteine↗
Discovery and evaluation of potent, tyrosine-based alpha4beta1 integrin antagonists.
Using disulphide cysteine-based inhibitors as lead structures, this communication describes our strategy for identifying more stable, potent antagonists of the alpha4beta1 integrin. These studies ultimately discovered potent, low molecular weight inhibitors based on D-thioproline-L-tyrosine.
Animals↗
Patent confusion in law on new plant varieties.
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Biotechnology↗
Dehydroepiandrosterone alters lipid profiles in Zucker rats.
High free fatty acid (FFA) levels are common in obesity and in diseases such as diabetes that are associated with the obese state. Dehydroepiandrosterone (DHEA) decreases dietary fat consumption, body fat content, and insulin levels in the obese Zucker rat (ZR), a genetic model of human youth-onset obesity and type 2 diabetes mellitus. This study was conducted to investigate the effects of DHEA on lean and obese ZR serum, adipose, and hepatic tissue fatty acid (FA) profiles and serum FFA levels. Because DHEA is known to decrease fat consumption and body fat, we postulate that DHEA may also alter FA profiles and FFA levels of the obese ZR such that they more closely resemble the profiles and levels of their lean siblings. In this study there was a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. The diet of the treatment groups was supplemented with 0.6% DHEA, and PF groups were given the same average calories consumed by their corresponding DHEA group for 30 d. Fasted animals were sacrificed, and FA profiles and FFA levels were measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared to lean rats (approximately 0.6 mmol/L). After 30 d of DHEA treatment, FFA levels were lower (P < 0.05) in both lean and obese groups. Although several significant differences in FA profile of serum, hepatic, and adipose lipid components were observed between lean and obese ZR, DHEA-related changes were only observed in the serum phospholipid (PL) and liver PL and triglyceride fractions. The slight but significant decrease in serum FFA levels may be reflected by changes in serum PL FA profiles. Specific hepatic FA profile alterations may be related to DHEA's known effects in inducing hepatic peroxisomes. We speculate that such FA changes may give insight into a mechanism for the action of DHEA.
Adipose Tissue↗
Dehydroepiandrosterone-mediated decrease in caloric intake by obese Zucker rats is not due to changes in serum entrostatin-like immunoreactivity.
To understand the mechanism(s) of appetite modulation by DHEA, we have undertaken a series of studies to examine the effects of DHEA on neurotransmitters and neuropeptides known to affect appetitive behavior. Here, we report the effect of DHEA on serum enterostatin-VPDPR or E, a pentapeptide known to cause selective diminution in fat intake. Four-week-old lean (fa/+) and obese (fa/fa) Zucker rats were divided into control and treatment groups. DHEA-treated groups received powdered chow containing 0.6% DHEA ad lib for 16 weeks. Another group of obese rats was pair fed to match the intake of the obese DHEA-treated rats. At the end of this period, trunk blood was collected from fasted rats for assay of E-like immunoreactivity (E-LI) by ELISA. DHEA treatment caused a significant diminution in circulating E-LI in both lean (control: 2030 +/- 226; treated: 752 +/- 145 ng/mL; n = 10, p < 0.0001) and obese (control: 2489 +/- 391, n = 6; treated: 1123 +/- 185 ng/mL, n = 7; p = 0.0003) rats. Because DHEA treatment decreases caloric intake and body weight, we examined the effect of caloric intake and body weight on E-LI levels. Serum ELI levels were lower in the obese DHEA-treated group compared to that of obese pair fed (pair fed: 1589 +/- 313, n = 6; DHEA: 1123 +/- 185 ng/mL, n = 7), but the differences were statistically insignificant (p = 0.185). Also, both weight-matched lean and obese control rats had significantly (p < 0.008) higher E-LI than their DHEA-treated counterparts. To examine whether the decrease in serum E-LI following DHEA treatment could be due to increased peptide metabolism, the rate of disappearance of endogenous E-LI from serum (obese control and DHEA-treated) at 37 degrees C was evaluated. The results show an attenuation of peptide metabolism in serum from DHEA-treated rats, a finding contrary to our expectations. In summary, DHEA treatment lowers serum E-LI levels both in lean and obese Zucker rats. This decrement in peptide level is not secondary to changes in body weight or caloric intake due to DHEA, or due to altered serum peptide metabolism. Although DHEA appears to be a potent modulator of E-LI levels, the relationship between DHEA and E-LI in relation to appetitive behavior remains to be clarified.
Animals↗
Serum leptin, lipids, free fatty acids, and fat pads in long-term dehydroepiandrosterone-treated Zucker rats.
The obese Zucker rat has a genetically flawed leptin system and is a model of hyperphagia, obesity, hyperlipidemia, and markedly elevated leptin levels. Dehydroepiandrosterone (DHEA) administration reduces hyperphagia, hyperlipidemia, and obesity in Zucker rats. Since serum leptin levels are associated with body fat, we wondered what the effects of fat pad weight reduction from DHEA administration would have on leptin levels. This experiment investigated the effects of DHEA on intra-abdominal fat pads, serum lipids, and peripheral leptin in male lean and obese Zucker rats that were administered DHEA in their food from 4 weeks of age to 20 weeks. Lean and obese rats received plain chow or chow containing DHEA. Additional chow-fed groups of lean and obese weight-matched controls and obese pair-fed rats helped to control for the reduced body weight, food intake, and fat pad weights seen with DHEA administration. DHEA administration to lean Zucker rats reduced body weight and fat pad weights, but leptin levels showed a lower trend. Among obese rats, both DHEA treatment and pair-feeding reduced body weight and fat pad weights, but only DHEA lowered leptin levels. The weight-matched controls had reductions in fat pad weights similar to the DHEA-treated group, but with increased leptin levels. Thus, DHEA may exert a small, independent effect on leptin levels in this animal model, but the reduction is less than what would be expected.
Adjuvants, Immunologic↗
Diagnostic peritoneal lavage as sole indicator of intraperitoneal bladder rupture: case report.
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Adult↗
Computerized tomography cystography for the diagnosis of traumatic bladder rupture.
PURPOSE: We present our experience with computerized tomography (CT) cystography for diagnosing bladder rupture in patients with blunt abdominal and pelvic trauma, and compare the results of CT cystography with those of surgical exploration. MATERIALS AND METHODS: We identified all patients with blunt trauma diagnosed with bladder rupture from 1992 to September 1998. We reviewed the radiology computerized information system for all CT cystography performed to evaluate blunt trauma during the same period. We also reviewed the medical records and pertinent radiographic studies of patients with bladder rupture who underwent CT cystography as part of the hospital admission evaluation. Operative and radiographic findings were compared. RESULTS: CT cystography was performed in 316 patients as part of the initial evaluation of blunt trauma. Of the 44 patients with the ultimate diagnosis of bladder rupture CT cystography revealed bladder rupture in 42, while 23 of the 28 (82%) who underwent formal bladder exploration had operative findings that exactly matched the CT cystography interpretation in terms of the presence and type of rupture. In the 316 patients CT cystography detected bladder rupture with an overall sensitivity and specificity of 95% and 100%, respectively. For intraperitoneal rupture sensitivity was 78% and specificity was 99%. CONCLUSIONS: CT cystography provides expedient evaluation of bladder rupture due to blunt trauma and has accuracy comparable to that reported for plain film cystography. We recommend CT cystography over plain film cystography in patients undergoing CT for other injuries associated with blunt trauma.
Adolescent↗
Synergistic anorectic effect of dehydroepiandrosterone and d-Fenfluramine on the obese Zucker rat.
Fasted obese, female Zucker rats accustomed to eating a single high fat meal within 1 h a day were treated with intraperitoneal injections of dehydroepiandrosterone (DHEA) and dextrofenfluramine (d-fen), either individually or in combination. Caloric intake was measured over a 1-h period 2 h after drug administration, and results compared to that of vehicle-treated controls. At 50 mg/kg body weight, DHEA did not affect food intake. At doses of < or = 2 mg/kg d-fen did not affect food intake. Together, however, DHEA 50 mg/kg and d-fen < or = 2 mg/kg significantly decreased food intake. At doses of > or = 3 mg/kg d-fen diminished caloric intake by itself, and the addition of DHEA significantly augmented this effect. Neurotransmitter levels in select regions of the hypothalamus of animals treated using a similar drug protocol showed several changes in the levels of serotonin and its metabolite 5 hydroxyindole acetic acid (5-HIAA). It is hypothesized that DHEA augments the production of serotonin while d-fenfluramine enhances its release, and together these two actions may account for the synergistic action of DHEA and d-fenfluramine.
Analysis of Variance↗
Long-term oral administration of dehydroepiandrosterone has different effects on energy intake of young lean and obese male Zucker rats when compared to controls of similar metabolic body size.
AIM: The effects of dehydroepiandrosterone (DHEA) on appetite and weight in the Zucker rat have been examined by many investigators who have reported appetite suppression and metabolic effects. However, these studies compared the treated animals to controls of a similar age. Since animals of different sizes consume different amounts of food, perhaps the treated animals should be compared to controls of a similar size. We studied the effects of DHEA on energy intake and weight gain and analysed the effects by age and metabolic body size. METHODS: Lean (n = 21) and obese (n = 16) male Zucker rats were fed plain chow or chow containing 6 g DHEA/kg chow (0.6% wt/wt) from age 4 wk to 20 wk. Daily energy intakes and body weights were determined at least once weekly. RESULTS: As expected, the lean and obese rats given DHEA exhibited less daily energy intake (kJ/d) and less weight gain than their respective controls of the same age. The lean rats given DHEA did not exhibit any difference in daily energy intake when determined relative to body weight (b.w.) (kJ x d-1 x g b.w.-1) compared to lean controls of the same metabolic body size, while the obese rats given DHEA exhibited less daily energy intake relative to b.w. (kJ x d-1 x g b.w.-1) compared to obese control of the same metabolic body size. CONCLUSIONS: Though DHEA reduced total energy intake among the lean and obese Zucker rats, only the obese rats exhibited less energy intake relative to b.w. compared to controls of the same metabolic body size. Thus, DHEA may exert different effects on energy intake relative to b.w. in lean and obese Zucker rats and perhaps the lean Zucker rat is a better model for evaluating the metabolic effects of DHEA since it does not exhibit any effect on energy intake relative to b.w. compared to rats of the same metabolic body size.
Animals↗
The beta-subunit of human chorionic gonadotrophin exists as a homodimer.
The free beta-subunit of human chorionic gonadotrophin (hCGbeta) is well recognised as a product of many epithelial tumours. Recently, it has been shown that this ectopic production may have a functional relationship to tumour growth. The growth-promoting activity of hCGbeta may be explained by its structural similarity to a family of growth factors which all contain the same distinct topological fold known as the cystine-knot motif. Since the other members of this family all exhibit their activities as homo- and heterodimers, it is possible that the same may be true for hCGbeta. Using size-exclusion chromatography, low stringency SDS-PAGE and matrix assisted laser desorption/ionisation (MALDI) time-of-flight (TOF) mass spectrometry (MS) we have shown that pure preparations of hCGbeta contain hCGbetabeta homodimers. Size-exclusion chromatography revealed asymmetric elution profiles with a forward peak corresponding to the size-exclusion characteristic of a globular protein with an approximate mass of 44-54 kDa and a late shoulder centered around an elution position expected for a globular protein of approximately 29 kDa. Two immunoreactive hCGbeta species, of approximately 32 and 64 kDa, were clearly resolved by SDS-PAGE and Western blotting. When analysed by MALDI-TOF MS a |mf23 kDa monomer and a |mf46 kDa dimer were identified. Formation of hCGbetabeta homodimers is consistent with the behaviour of other cystine-knot growth factors and strengthens the inclusion of the glycoprotein hormones within this superfamily. It has yet to be determined whether it is this dimeric molecular species that is responsible for growth-promoting activity of hCGbeta preparations in tumours.
Blotting, Western↗
A 16-element phased-array head coil.
Volume-array coils offer increased signal-to-noise ratio (SNR) over standard volume coils near the array elements while preserving the SNR at the center of the volume. As the number of array elements is increased, the SNR advantage as well as the complexity of actually constructing the array increases also. In this study, a 16-channel receive-only array for imaging of the brain is demonstrated and compared to a circularly polarized (CP) head coil of similar shape and diameter. The array was formed from a 2 x 8 grid of square elements placed on a cylindrical form. Mutual coupling was minimized by a combination of overlapping element placement and current-reducing matching networks. Simultaneous data acquisition from the 16 individual elements was performed using a four-channel receiver system with each channel time domain multiplexed by a factor of 4. Theoretical and experimental comparisons between the array and a standard CP head coil show that the array offers an increase in SNR of nearly a factor of 3 near its surface while maintaining a comparable SNR to that of the CP head coil in the center of the region of interest.
Brain↗
The actions of exogenous dehydroepiandrosterone in experimental animals and humans.
Dehydroepiandrosterone (DHEA) is the major adrenal steroid of young adults; however, its physiologic functions, if any, are not known. The purpose of this review is to evaluate the current literature in which DHEA was administered to either humans or experimental animals to discern what these functions might be. Reports are divided into five areas: neurologic, immunologic, cardiovascular, oncologic, and metabolic. Particular attention is paid to the dosage and route of administration. This type of analysis shows that at the lowest doses, DHEA has effects on neurologic and immunologic tissues, suggesting that these two sites may be physiologic targets. DHEA also affects cardiologic and metabolic functions as well as tumor growth, but such actions require higher doses and may reflect 'pharmacologic' activities. It is proposed that DHEA's pattern of activity represents a new class of steroid hormones, the "Regnantoids." Further progress in the endocrinology of this family of steroids may only come when synthetic, long-acting analogs of DHEA are available for in vitro studies to allow correlations between hormone action and receptor binding.
Animals↗