Search PubMed⌕ Search

Biomedical subjects

J R Porter

Publications and source records attributed to J R Porter.

At least 55 records · Page 3Linked to original sources

Dietary and hypothalamic changes in delta 4-androstenedione-treated Zucker rats.

Dehydroepiandrosterone (DHEA) has been shown to alter hypothalamic monoamines and reduce energy intake (EI) in Zucker rats (ZRs). We hypothesized that a metabolite of DHEA, delta 4-Androstenedione (delta 4), may mediate these effects. Male lean and obese ZRs (LZR, OZR) were fed control chow (CC) for 7 days, during which basal EI was recorded, various concentrations of delta 4 for 7 days, during which 0.6 and 0.3% delta 4 reduced EI significantly, and CC for 7 days, which resulted in a return of EI to basal levels. After delta 4 administration, neurotransmitter contents of various hypothalamic areas were determined. Serotonin (5-HT) has been shown to be correlated with feeding inhibition, and we have shown DHEA to increase lateral hypothalamic 5-HT synthesis; however, after 1 day and 7 days of delta 4, the OZR exhibited an increased metabolism, not synthesis, of 5-HT in the lateral and paraventricular hypothalamus, respectively, delta 4 was compared to DHEA in a macronutrient self-selection study with female OZRs. One group was injected intraperitoneally (IP) with sesame oil (control), another with DHEA (100 mg/kg), and another with delta 4 (100 mg/kg). Previous studies have shown that DHEA decreases both EI and % calories from fat. In this study, delta 4 decreased % calories from fat, but did not decrease total EI. Contrary to DHEA's effect of reducing serum insulin through 28 days of treatment, delta 4 in chow reduced insulin only acutely (1 day). We conclude, based on these differences, that DHEA has unique effects not mediated by its metabolite, delta 4-Androstenedione.

Androstenedione↗

Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor.

In this study, we describe the activity of CT1746, an orally-active synthetic MMP inhibitor that has a greater specificity for gelatinase A, gelatinase B and stromelysin than for interstitial collagenase and matrilysin, in a nude mouse model that better mimics the clinical development of human colon cancer. The model is constructed by surgical orthotopic implantation (SOI) of histologically-intact tissue of the metastatic human colon tumor cell line Co-3. Animals were gavaged with CT1746 twice a day at 100 mg/kg for 5 days after the SOI of Co-3 for 43 days. In this model CT1746 significantly prolonged the median survival time of the tumor-bearing animals from 51 to 78 days. Significant efficacy of CT1746 was observed on primary tumor growth (32% reduction in mean tumor area at day 36), total spread and metastasis (6/20 treated animals had no detectable spread and metastasis at autopsy compared to 100% incidence of secondaries in control groups). Efficacy of CT1746 could also be seen on reducing tumor spread and metastasis to individual organ sites such as the abdominal wall, cecum and lymph nodes compared to vehicle and untreated controls. We conclude that chronic administration of a peptidomimetic MMP inhibitor via the oral route is feasible and results in inhibition of solid tumor growth, spread and metastasis with increase in survival in this model of human cancer, thus converting aggressive cancer to a more controlled indolent disease.

Amides↗

Traumatic posterior urethral injury and early realignment using magnetic urethral catheters.

PURPOSE: We determined the success of early urethral realignment using magnetic urethral catheters. MATERIALS AND METHODS: We retrospectively reviewed the records of 13 patients with complete urethral disruption treated with endourological realignment 0 to 11 days after injury using coaxial magnetic urethral catheters. RESULTS: Urethral realignment was established in 11 of the 13 patients (85%) using magnetic urethral catheters. Of the 10 patients for whom followup was available urethral strictures developed in 5 (50%) a mean of 6.1 months after realignment, necessitating a mean of 1.4 corrective procedures per patient. Impotence was noted in 1 of 7 patients (14%) and no urinary incontinence developed after realignment. CONCLUSIONS: Urethral realignment within 2 weeks of injury using magnetic urethral catheters is a safe and simple technique with minimal morbidity. The stricture formation, impotence and incontinence rates of this technique are comparable to those reported for delayed urethroplasty. We advocate early realignment using magnetic urethral sounds as an alternative treatment for traumatic urethral disruption.

Adolescent↗

A paradoxical elevation of brain cyclo(His-Pro) levels in hyperphagic obese Zucker rats.

Several studies suggest a role for endogenous cyclo(His-Pro) or CHP in appetite regulation. In the present study, we have examined the regional brain distribution of CHP in hyperphagic obese Zucker rats and their lean littermates. The data show a significant elevation in the levels of CHP in many brain regions, including hypothalamus of the obese rat. Within the hypothalamus, the lateral hypothalamic (LH) nucleus of obese rats had significantly higher levels of CHP when compared to that of the lean littermates. Administration of dehydroepiandrosterone, a steroid hormone known to decrease food intake and body weight gain, to obese rats led to decrease in the levels of CHP in the LH. These data further suggest a role for the endogenous CHP in attenuating food intake.

Animals↗

Design of matching networks for low noise preamplifiers.

This paper discusses matching networks that minimize inductive coupling between the antennas within an array while simultaneously insuring minimum noise contributions from preamplifiers. Typical low noise preamplifier designs require a strong mismatch between the source impedance and the amplifier input impedance (reflection coefficient close to one) to achieve optimal noise performance. This is in contrast to the familiar impedance match known from communication theory where input and source impedances have complex conjugate values for maximizing the power transfer from source to amplifier. The high input reflection coefficient of low noise amplifiers can be exploited to reduce antenna currents by using lossless impedance transformations to create a high impedance at the coil terminals while simultaneously maintaining a low noise figure for the amplifier. The networks presented here constitute an improvement over previous work because they give additional freedoms regarding the values of the network components and the amplifier input impedance. The technique has been formalized and coded in MathCad, making the design of realizable networks a simple process.

Magnetic Resonance Imaging↗

Dehydroepiandrosterone and macronutrient selection by obese Zucker rats (fa/fa).

The effect of dehydroepiandrosterone (DHEA) on the macronutrient preference and total energy intake of lean and obese female Zucker rats was studied. Introduction of DHEA led to a rapid decrease in the consumption of fat, protein and total calories by the obese rat. DHEA treatment of the lean rat caused a change neither in its total energy consumption nor in its fat consumption, but did cause a distinct expression of preference for carbohydrate over protein. Both lean and obese animals gained weight rapidly during the steroid-free weeks and lost weight while consuming the DHEA-supplemented diet. The difference in weight changes seen with the obese rats between the DHEA-free and DHEA-supplemented periods could be accounted for by differences in caloric intake. Lean rats, however, did not change their total energy intake during DHEA-treatment periods; therefore, DHEA caused weight loss in the lean rat probably by altering energy metabolism. It is concluded that in the obese, young, female Zucker rat, DHEA alters macronutrient preference as well as caloric intake. In the lean rat, DHEA has a more subtle effect on relative macronutrient preference and not on total energy consumption.

Animals↗

The effect of DHEA given chronically to Zucker rats.

Dehydroepiandrosterone (DHEA) has been reported to exert antiglucocorticoid activity. When administered to obese, hypercorticosteronemic Zucker rats, it causes a diminution of food intake and a reduction in their rate of weight gain. This experiment was conducted to evaluate whether this biologic effect could be ascribed to chronic adrenal insufficiency. Obese and lean Zucker rats were treated with DHEA as a food supplement for 28 days. Upon sacrifice, organ weights and serum chemistries were measured, along with neurotransmitter levels in regions of the hypothalamus. Results showed that although the obese animals gained weight more slowly, had lower insulin levels, and ate less, their serum glucose, corticosterone, and ACTH levels were not different from control. Hypothalamic neurotransmitters in the obese rat were unaffected by chronic DHEA treatment. We concluded that, although DHEA clearly affects Zucker weight gain, it does not induce chronic adrenal insufficiency.

Adrenal Glands↗

The effect of discontinuing dehydroepiandrosterone supplementation on Zucker rat food intake and hypothalamic neurotransmitters.

OBJECTIVE: Dehydroepiandrosterone (DHEA) decreases body weight and food intake of the obese Zucker rat, a model of youth-onset obesity associated with hyperphagia. The effects of discontinuing DHEA treatment on these parameters, however, has not been investigated. This question was studied in rats that had been maintained on DHEA-supplemented (0.0%, 0.06%, 0.15%, 0.3% or 0.6%) diets for 7 days. METHOD: The results were correlated with regional levels of hypothalamic neurotransmitters in rats treated with 0.6% DHEA for 7 days in a separate experiment. Neurotransmitter changes were evaluated after Day 0 (7 days of treatment), and Day +1 and Day+2 post-DHEA. RESULTS: Upon removing dietary DHEA, rats immediately (+1 day) consumed significantly more food than while on the DHEA-supplemented diet. Indeed, they consumed even more food than the group that had always been on the DHEA-free diet. This intake above control lasted for as long as +9 days post-DHEA treatment. After 7 days of DHEA treatment, lateral hypothalamic (LH) serotonin (5-HT) and dopamine (Dpm) were elevated significantly (P < 0.05) immediate changes in 5-HT and Dpm returned to baseline by day 2 of post-DHEA treatment. No significant changes occurred in either the ventromedial hypothalamus (VMH) or the paraventricular nucleus (PVN). CONCLUSIONS: These observations suggest that there is a possible relationship between increases of LH 5-HT and Dpm with 0.6% DHEA treatment. Both are inhibitory to food intake and DHEA at the 0.6% dose causes hypophagia after 7 days of treatment (i.e. 0 days). Subsequent decreases of these monoamines occurred during the post-DHEA period at both +1 and +2 days. Return of these inhibitory monoamines to baseline could be responsible for reversal of the hypophagia, however, they do not rule out the production of a separate stimulator of food intake.

Androstenedione↗

Central effects of dehydroepiandrosterone in Zucker rats.

OBJECTIVES: To investigate whether dehydroepiandrosterone (DHEA), an adrenal/gonadal androgen, can act centrally to reduce energy intake in a model of genetic obesity, the Zucker fatty rat. To investigate a possible mechanism of action. DESIGN: Two experiments were performed in lean and obese female Zucker rats. In the first experiment, 24 h following administration of i.p. DHEA (200 mg/kg), three hypothalamic regions [lateral hypothalamus (LH), ventromedial nucleus (VMH), and paraventricular nucleus (PVN)] were analyzed for monoamine neurotransmitter concentrations. In the second experiment, DHEA (50 micrograms) was administered by i.c.v. injection. Energy intake for the following day was measured. MEASUREMENTS: In the first experiment, concentrations of norepinephrine (NE), epinephrine (EPI), dopamine (DA), serotonin (5HT), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured. Ratios of 5HT/5HIAA were calculated. In the second experiment, kilojoules consumed per 24 h were calculated. RESULTS: All LH monoamines, and PVN DA, displayed lower concentrations in obese than lean control rats. DHEA treatment reversed these reductions in obese rats without affecting lean rats. DHEA increased VMH EPI in obese rats only. DHEA increased PVN NE in both lean and obese rats. I.C.V. DHEA decreased energy intake in obese but not lean rats. CONCLUSION: The i.c.v. results suggest that DHEA exerts a phenotype specific, centrally mediated inhibitory effect on food intake. In addition, in doses previously shown to reduce energy intake in obese but not lean rats, i.p. DHEA reversed reduced concentrations of many monoamines, particularly in the LH, in obese animals only. These latter changes provide indirect evidence to suggest that these central neurotransmitters may play an important role in the antiobesity effect of DHEA in the Zucker fatty rat.

Animals↗

A four-channel time domain multiplexer: a cost-effective alternative to multiple receivers.

The concept of simultaneous image acquisition as originally conceived by Hyde has been implemented by Roemer et al. using a multiple receiver system. This article describes an alternative technique that uses time domain multiplexing (TDM) to acquire simultaneous images using a single receiver channel. This method requires few modifications to the existing receiver and has been shown to be equivalent to a true four channel receiver in most applications. The multiplexing technique was implemented and tested on a standard commercial scanner that has also been equipped with a four channel receiver. Signal-to-noise results demonstrate that four independent images can be multiplexed through a single receiver channel with no degradation in image quality. Additionally, spine images that were obtained from a normal volunteer with both a multiplexed single channel receiver and a true four channel receiver system are presented.

Cost-Benefit Analysis↗

Does taste aversion play a role in the effect of dehydroepiandrosterone in Zucker rats?

Dehydroepiandrosterone (DHEA) reduces food intake in obese Zucker rats. To study the role of taste aversion on this process, we used two approaches. First, we presented increasing concentrations of DHEA in chow to lean and obese Zucker rats, either in competition with unadulterated chow, or alone. Second, we examined energy intake following parenteral DHEA administration. Both lean and obese rats always preferred nonadulterated chow to DHEA-supplemented chow. However, lean rats required a higher DHEA concentration (0.06%) than obese rats (0.015%) to achieve the same degree of aversion. When DHEA-supplemented chow was presented alone, only high concentrations (0.3 and 0.6% DHEA) decreased food intake. Rats given DHEA by IP injection (200 mg/kg/day) also decreased their energy intakes. The results demonstrate that although DHEA can cause taste aversion at low concentrations in Zucker rats, it does not alter energy intake until high concentrations are given. In addition, nonoral DHEA also decreases energy intake in these animals. These results suggest that DHEA's antiobesity effect is not mediated by taste aversion.

Administration, Oral↗

Toluene removal from air by Dieffenbachia in a closed environment.

Higher plants are likely to play a major role in bioregeneration systems for food, air and water supplies. Plants may also contribute by the removal of toxic organic substances from the air of a closed environment. Dieffenbachia amoena plants were exposed to 0 to 1.2 x 10(6) micrograms toluene m-3 at light intensities of 35 and 90 micromoles m-2 s-1 in sealed chambers. Toluene removal, photosynthesis and respiration were measured. An increased light intensity increased the rate of toluene removal five-fold over the rate at the lower intensity; the kinetics suggest active regulation by the plant. The removal rate saturated at 2700 micrograms toluene h-1 at the lower intensity and failed to saturate at the higher intensity. Toluene exposure inhibited photosynthesis and respiration only transiently and without correlation to toluene concentration. These plants can act as efficient scavengers of toluene in a contaminated environment.

Air Conditioning↗

The effect of a racially consonant medical context on adjustment of African-American patients to physical disability.

The effect of a racially consonant medical context on reaction to physical handicap stemming from disease is explored in a sample of 90 African-American patients with vitiligo, a disfiguring skin disorder. The adjustment of sixty-nine patients in a predominantly black hospital setting is compared to that of twenty-one patients in a predominantly white hospital setting. The patients in the predominantly black clinic, where the physicians, staff, and clientele are African-American, show significantly better adjustment than do African-American patients in a medical context that is primarily white. Interviews with a random sample of one-third of the patients in each clinic show that patients are significantly more positive to black physicians and a black hospital setting and that other patients of the same race provide informal networks of support, as does the predominantly African-American community in which the hospital is located. Implications for both medical theory and practice are suggested on the basis of these findings.

Adult↗

Prostatic intraepithelial neoplasia and prostate-specific antigen.

Prostatic intraepithelial neoplasia (PIN) is a putative premalignant lesion of the prostate gland. PIN has been demonstrated to share morphologic and phenotypic similarities to invasive carcinoma of the prostate. In addition, PIN is spatially related to invasive carcinoma and occurs with greater frequency in men whose prostates harbor carcinoma. Prostate-specific antigen (PSA) is a glycoprotein produced by the prostatic epithelium. For PSA to be detected in the serum, it must traverse several tissue layers to reach the circulatory system. PSA levels associated with PIN are intermediate between those of benign and malignant prostate tissue. Spatially associated occult carcinoma, disruption of the basal cell layer, and increased vascularity may account for elevated PSA values in PIN.

Humans↗

Divergent effect of dehydroepiandrosterone on energy intakes of Zucker rats.

Oral dehydroepiandrosterone (DHEA) causes weight loss in the obese Zucker rat. To study this process, we fed lean and obese female Zucker rats either control chow diets alone or diets containing 0.6% DHEA for 4 weeks. DHEA treatment led to a significant increase in the caloric intake of lean-treatment rats and a significant decrease in obese-treatment rats compared to their respective controls. These phenotype-specific divergent effects began acutely and were sustained. The energy intake changes with DHEA treatment were significant after correcting for body weight. Divergent effects of DHEA were also observed in body weight changes and in the food efficiency ratios of the animals; DHEA affected obese rats but not lean ones. The results of the present study suggest that the appetite component of DHEA's antiobesity effect in the Zucker fatty rat cannot be discounted.

Animals↗

Dehydroepiandrosterone regulation of the hepatic glucocorticoid receptor in the Zucker rat. The obesity research program.

Dehydroepiandrosterone (DHEA) decreases the activity of hepatic tyrosine aminotransferase (TAT), a glucocorticoid-inducible enzyme, in the obese, hypercorticosteronemic Zucker rat. To investigate the mechanism of this antiglucocorticoid action, the effect of exogenous DHEA on hepatic glucocorticoid receptor (GC) number and affinity was quantitated. Food supplementation with DHEA (0.6% w/w) for 1 or 7 days had no effect on either receptor number or affinity in obese Zucker rats. After 28 days, however, DHEA treatment resulted in a nearly 40% decrease in cytosolic hepatic receptor content (Bmax; fmol/mg cytosolic protein) without any change in affinity (Kd) in both lean and obese rats. DHEA treatment for 28 days also resulted in an increased liver size and cytosolic protein content. When the hepatic GC receptor content was normalized based on the change in liver size and protein content, the apparent number of GC binding sites per liver was not affected by DHEA treatment. This observation suggests that DHEA's effect on GC receptor content may not be a specific action and that downregulation of the GC receptor is not the mechanism of DHEA action on GC induced TAT activity. This is supported by the effect of DHEA on obese rat TAT activity in the same experiment where the greatest inhibition occurred after only 1 day of treatment. From these experiments it is concluded that although long-term DHEA treatment may decrease the relative concentration of GC receptors in rat liver, this change is not the mechanism through which DHEA mediates its acute antiglucocorticoid action.

Animals↗