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Biomedical subjects

J R Porter

Publications and source records attributed to J R Porter.

At least 73 records · Page 4Linked to original sources

Immunoassay of podophyllotoxin.

The purpose of our research was to design and develop a sensitive immunoassay for the natural Podophyllum lignan, podophyllotoxin [1], which is the precursor of the anti-cancer drugs etoposide [2] and teniposide [3]. In order to obtain a specific antiserum, bovine serum albumin and keyhole limpet hemocyanin conjugates of succinyl-podophyllotoxin [5] were prepared as antigenic hapten carrier proteins. These antigens were used to develop polyclonal antibodies to 1 in rabbits. The antisera were used for the development of an immunoassay for the detection of 1 and its 4'-demethyl derivative 4. As little as 0.16 nmol of 1 is detectable with this ELISA. The assay was applied to the direct analysis of 1 in plants for the screening of potential drug plants which allowed quantitation in less than 0.2 mg of plant tissue.

Animals↗

MR flow measurement using RF phase gradients in receiver coil arrays.

Radio frequency (RF) phase gradients in the receiver coil field pattern can encode flow velocity information in magnetic resonance (MR) images in the form of phase variations. These phase variations are not readily observed in MR images because they are relatively small compared to phase variations caused by static magnetic field (B0) inhomogeneities, susceptibility variations, and other sources. However, the phase contributions from these other sources are independent of the receiver coil. Therefore, the RF phase gradient encoded flow information can be recovered by subtracting images obtained simultaneously using arrays of independent receiver coils and a multiple channel receiver. This flow velocity information can be extracted retrospectively from standard imaging sequences, including flow-compensated sequences. No additional time is required for the flow study as the flow measurements are made using sequences chosen for optimal imaging, and the images from each coil are obtained simultaneously. Initial results indicate that sufficient sensitivity is obtained to make flow measurements in the range of velocities commonly found in the carotid arteries and other major vessels. In principle, the method works with only two receiver coils. However, additional elements provide additional phase measurements that can be used to increase accuracy, remove ambiguities in flow direction or velocity calculations, and increase the region over which velocity measurements can be accurately made.

Artifacts↗

Effect of dehydroepiandrosterone on neurotransmitter levels and appetite regulation of the obese Zucker rat. The Obesity Research Program.

The obese Zucker rat is a model of youth-onset obesity associated with hyperphagia. In this study, dehydroepiandrosterone's effect at decreasing food intake and body weight in the obese Zucker rat was investigated. Rats were treated with a dehydroepiandrosterone-supplemented diet (0.0, 0.06, 0.15, 0.3, or 0.6%) for 7 days. The 0.3 and 0.6% treatment groups showed a dramatic decrease in daily food intake, which was evident the 1st day. In addition to the reduction in food intake, body weight changes also were affected significantly in the high-dose treatment groups. The possibility that these dehydroepiandrosterone-induced changes were correlated to perturbations in central neurotransmitter levels associated with appetite control was investigated. The hypothalamus, frontal cortex, striatum, and hippocampus of dehydroepiandrosterone-treated animals were assayed for neurotransmitters known to have inhibitory or stimulatory effects on feeding behavior (serotonin, dopamine, norepinephrine, and epinephrine). Significant differences from steroid-free controls were noted only in the levels of hypothalamic serotonin in animals treated with dehydroepiandrosterone. Serotonin in the hypothalamus has been shown to decrease feeding behavior. The magnitude of dehydroepiandrosterone's effect on hypothalamic serotonin correlated with its effect on feeding behavior. Thus, dehydroepiandrosterone may reduce hyperphagia by altering hypothalamic levels of serotonin.

Androgens↗

Dehydroepiandrosterone: antiglucocorticoid action in mice.

The acute effect of dehydroepiandrosterone (DHEA) and its conjugate, DHEA-sulfate (DHEA-S) on glucocorticoid action was tested in vivo using male Swiss-Webster mice. The authors found that DHEA and DHEA-S significantly inhibited induction of hepatic tyrosine aminotransferase activity, although the former was more potent. This inhibition was dose- and time-dependent and was not demonstrable with other steroids. The same inhibitory effect of DHEA was seen with kidney tyrosine aminotransferase induction, as well as with liver and kidney ornithine decarboxylase enzyme activity, another glucocorticoid-induced enzyme. The conclusion is that DHEA acts acutely as an antiglucocorticoid and exerts its effect in different glucocorticoid-sensitive systems.

Adrenalectomy↗

Is there a role for the adrenals in the development of hypercholesterolemia in Zucker fatty rats?

We tested the hypothesis that hypercorticosteronemia causes the hypercholesterolemia in young developing "fatty" rats. Obesity induced increases in corticosterone. Insulin, glucose, body weight, average daily food intake, plasma triglyceride, plasma phospholipids, liver weight, liver triglyceride, various adipose tissue parameters, and liver hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity were all ameliorated by adrenalectomy. Adrenalectomy exacerbated the hypercholesterolemia in obese animals and induced it in lean rats. Changes or lack of change in hepatic microsomal cholesterol, HMG-CoA reductase, and 7 alpha-hydroxylase, combined with the adrenalectomy-induced curtailment of tissue storage of cholesterol in adipose tissue, all contribute to the hypercholesterolemia caused by adrenalectomy. We suggest a mechanism whereby this may be related to elevated hepatic very low-density lipoprotein secretion rates. The elevated HMG-CoA reductase activity in obese rats results from the lower liver microsomal free cholesterol content. We conclude that the absence of glucocorticoids does not directly reduce plasma cholesterol in obese Zucker rats. The surprising elevation of cholesterol by adrenalectomy is due to other prevailing mechanisms in liver and adipose tissue, which curtail their capacity to store cholesterol.

Adipose Tissue↗

Antiglucocorticoid action of dehydroepiandrosterone in young obese Zucker rats.

Dehydroepiandrosterone (DHEA) reduces weight gain in the hypercorticosteronemic Zucker fatty rat, an animal model of genetic obesity. However, the mechanism of action of DHEA is still unclear. We propose that DHEA acts as an antiglucocorticoid in the Zucker fatty rat. To test this hypothesis we examined DHEA's ability to block the activation of the glucocorticoid-inducible enzymes tyrosine aminotransferase (TAT) and ornithine decarboxylase (ODC) by dexamethasone (i.p. 5 micrograms/100 g body weight) in hepatic tissue of 6-10 week old Zucker rats. Injections of DMSO, the vehicle, served as a control. DHEA alone did not affect TAT, but when DHEA (500 micrograms/100 g b.w.) was administered simultaneously with dexamethasone, activation did not occur. Similar results were seen using a second tissue (kidney). We conclude that DHEA can act acutely as an antiglucocorticoid in the young obese Zucker rat and hypothesize that its chronic anti-obesity effect may reflect, at least in part, a chronic antiglucocorticoid activity.

Analysis of Variance↗

Racial variation in reaction to physical stigma: a study of degree of disturbance by vitiligo among black and white patients.

The effect of race on reaction to impaired appearance is explored in a sample of 158 patients with vitiligo, a disfiguring skin disease. Blacks and Whites do not differ in degree of disturbance by the disorder. Psychological coping resources and variables related to negative labeling of the stigma are associated with variation in degree of disturbance. Self-esteem and perceived stigmatization are associated significantly with degree of disturbance among both Blacks and Whites. Gender, age, and visibility of the condition are not related to difference in degree of disturbance within either race, although there is some evidence that they may have an indirect relationship to degree of disturbance. Importance of appearance is associated with degree of disturbance for Whites only, because of the threat of the depigmentation induced by vitiligo to the racial identity of Blacks. The implications of these findings for theory and practice are discussed.

Adaptation, Psychological↗

The effect of vitiligo on sexual relationships.

To study the effect of vitiligo on interference with sexual relationships, we surveyed 158 patients by questionnaire. Although a majority of patients reported a negative impact on sexual relationships, most patients felt embarrassment when showing their body or meeting strangers. The majority of patients who reported a negative impact on sexual relationships attributed the problems to their embarrassment. Those who were particularly affected were those with low self-esteem, men, those to whom appearance is important, and single persons. Dermatologists should be especially alert to the effects of disfigurement and should attempt to assist patients with this problem.

Adolescent↗

The metabolic clearance rate of corticosterone in lean and obese male Zucker rats.

The obese Zucker rat is an animal model of human juvenile-onset obesity. These rats exhibit numerous endocrine and metabolic abnormalities. Adrenalectomy of obese rats has been shown to reduce or reverse several of these abnormalities, thereby implying that corticosterone may contribute to the expression of obesity in this animal. Furthermore, it has been shown that the circadian rhythm of plasma corticosterone is disturbed in obese Zucker rats resulting in elevated morning plasma corticosterone concentrations in obese rats as compared to lean rats. In a effort to better elucidate the mechanism of the elevated morning levels of plasma corticosterone, the metabolic clearance rate of corticosterone was determined in the morning for lean and obese male Zucker rats (12 to 20 weeks). Additionally, the biliary and urinary excretion of labeled corticosterone and/or its metabolites were determined. The metabolic clearance rate of corticosterone was significantly greater in obese rats than in their lean counterparts. Both the metabolic clearance rate and the volume of compartments significantly correlated with body weight. No correlation was found between body weight and the elimination rate constant. The increased metabolic clearance rate of obese rats appeared to be due to an increase in the physiologic distribution of corticosterone and not to an alteration in the enzymes responsible for corticosterone metabolism. It appears that the metabolic clearance rate of corticosterone in obese Zucker rats does not contribute to elevated morning concentrations of plasma corticosterone previously observed in these animals. It suggests that the adrenal corticosterone secretion rate must actually be greater than one would expect from the plasma corticosterone concentrations alone.

Animals↗

Decreased [3H]-naloxone binding and elevated dynorphin-A(1-8) content in Zucker rat brain.

We have previously reported that female obese Zucker rats are hypersensitive to painful stimuli and are resistant to the analgesic effects of morphine. In continuation we hypothesized that these phenomena are possibly the result of diminished population of opioid receptors, or an overabundance of dynorphin interfering with morphine analgesia. We now report that female obese Zucker rats have decreased concentrations of mu opioid receptors in whole brain and elevated levels of Dynorphin A(1-8) (DYN) in a brain area known to be associated with responses to nociceptive stimuli.

Animals↗

Responsiveness of isolated adrenocortical cells from lean and obese Zucker rats to ACTH.

Morning plasma corticosterone concentrations have been reported to be elevated in obese Zucker rats compared with lean rats. The aim of this study was to determine if differences in adrenal sensitivity or maximal responsiveness to adrenocorticotropic hormone (ACTH)-(1-24) could account for this disparity. Serum and adrenal glands were collected from lean and obese, male and female Zucker rats (10-13 wk old) between 10:00 and 11:00 A.M. Adrenocortical cells were isolated and challenged with ACTH-(1-24). The serum corticosterone and ACTH concentrations were significantly greater in obese males compared with lean males (45.3 +/- 10.3 vs. 23.2 +/- 1.45 ng/ml and 156.6 +/- 15.3 vs. 113.3 +/- 9.4 pg/ml, respectively). Although serum corticosterone concentrations were similar in female rats, serum ACTH concentrations tended (P = 0.07) to be lower in obese female rats than in lean female rats (67.6 +/- 9.3 vs. 103.5 +/- 15.1 pg/ml, respectively). The median effective concentration (EC50) and the maximal corticosterone response per microgram of DNA of dose-response curves derived from lean and obese rats were not significantly different. Additionally, a morphometric evaluation of adrenal tissue from lean and obese rats suggested that cells of the zona glomerulosa were smaller in obese rats than in lean rats. Our data confirm that morning serum corticosterone concentrations are elevated in 10- to 13-wk-old male Zucker rats. This difference does not appear to be due to differences in the sensitivity or maximal secreting capacity of adrenocortical cells to ACTH.

Adrenal Cortex↗

Interaction of temperature with other environmental factors in controlling the development of plants.

Development is the ordered sequence of changes in plant form and phenology that occurs through time. As such it is distinguished from that of growth and includes the succession of ontogenetic stages as well as the initiation of leaves, shoots and roots. It is more useful to look at rates of development as functions of environmental influences rather than, for example, total number of days to a given stage. It is often found that linear, or close to linear, relationships are found between rates and temperature, photoperiod and the duration of cold temperatures. These ideas are treated theoretically and illustrated with data from an experiment where wheat was grown at ten sites in Britain. We conclude that temperature is the most important factor governing differences in developmental rates between sites and sowing dates, especially for later stages of development. Variation in the timing of earlier stages depends on either exposure to photoperiods of different lengths or on the degree of vernalization of the plants. Calculation is made of the maximum effectiveness of these environmental factors in shortening the vegetative phases in a range of wheat cultivars and the basis of their interaction is also explored. For wheat it seems that they act multiplicatively in their effect on developmental rate. The rate at which plants produce their leaves is important in canopy development. The sensitivity of the rate of leaf emergence, measured in thermal time, has been linked to the rate at which daylength changes (d phi/dt). A possible mechanism may involve plants responding to the ratio of light in the red (R, ca 660 nm) and far-red (FR, ca 730 nm) wavebands (R/FR). This ratio decreases when d phi/dt is becoming more negative and vice versa. Linkage can be found between the change in R/FR at twilight and commensurate changes in calculated phytochrome photoequilibria. Thus, the possibility exists that phytochrome may be involved in modulating the leaf production rate in response to different sowing dates. Alternatively, variation in rate of leaf production may be through changes in the base temperature, in response to the 'spectrum' of temperatures the plants experience during development. Thus, any involvement of photoperiod in this response may be spurious. Controlled environment studies of leaf emergence tend to support this latter interpretation as does analysis of experiments from three European sites.

Edible Grain↗

Nociception and opioid-induced analgesia in lean (Fa/-) and obese (fa/fa) Zucker rats.

Previous research indicates a possible interrelationship between the endogenous opioids (EO), nociception and food-intake. We therefore considered the hyperphagic obese Zucker rat a good candidate for abnormal responses to nociceptive stimuli. Pairs of lean and obese sisters were tested for latency of response to nociceptive stimuli by tail-flick and tail-pinch methods. Obese rats exhibited shorter latencies in each test, (tail-flick, p less than 0.05 and tail-pinch, p less than 0.001). Dose/response curves for morphine analgesia indicate that morphine is less potent in obese than in lean rats (ED50's = 4.87 +/- 0.62 mg/kg and 3.12 +/- 0.41 mg/kg respectively, p less than 0.05). These data suggest a defect in the EO systems of obese Zucker rats.

Animals↗

Psychosocial effect of vitiligo: a comparison of vitiligo patients with "normal" control subjects, with psoriasis patients, and with patients with other pigmentary disorders.

To ascertain the psychosocial effects of vitiligo, patients with vitiligo were compared with control subjects without skin diseases who were matched for age, sex, race, educational level, and marital status. Vitiligo patients were also compared with a matched sample of psoriasis patients and a matched sample of patients with other pigmentary disorders involving discoloration. The vitiligo patients scored lower on the Coopersmith Self-Esteem Inventory than did the "normal" control subjects. Vitiligo patients exhibited better adjustment to their disorder and experienced less social discrimination than did psoriasis patients, although the two groups did not differ on overall self-esteem. Patients with vitiligo did not differ significantly from those with other pigmentary disorders on any measure.

Adaptation, Psychological↗

Adenohypophyseal response to hypophysiotropic hormones in male obese Zucker rats.

Description of the recessive, homozygote obese Zucker rat (fafa) includes disorders of growth and reproduction. The aim of this study was to compare responsiveness of adenohypophyseal cells, obtained from male fafa rats and from their lean siblings, to growth hormone-releasing factor (GRF) and to luteinizing hormone-releasing hormone (LHRH). Pituitary cells were cultured for 4 days and were then challenged with either GRF-29 (the NH2-terminal 29 amino acid GRF peptide that expresses full biological activity of its parent 44 amino acid molecule) or [D-Trp6]LHRH (LHRH-A, an LHRH agonist). Medium was assayed for growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by radioimmunoassay. Dose-response curves were compared using the computer program ALLFIT. The median effective GRF-29 concentration (EC50) computed for hypophyseal cells cultured from lean animals (0.30 +/- 0.01 fM; means +/- SE of 4 experiments) was less (P less than 0.01) than that calculated for cells obtained from fafa rats (15.8 +/- 6.7 fM). In contrast, cells derived from lean littermates required a larger (EC50) concentration of LHRH-A than did gonadotrophs cultured from obese rats [58.2 +/- 1.2 vs. 10.7 +/- 1.2 pM (P less than 0.01) and 59.4 +/- 10.4 vs. 15.7 +/- 7.6 pM (P less than 0.05)] to secrete LH and FSH, respectively. Our data describe an attenuated pituitary response to GRF-29 and an enhanced response to LHRH-A in the fafa.

Animals↗

Malnutrition and oxygen at high pressure: influence on collagen synthesis in lung and heart of the newborn rat.

Rat dams were divided into a malnourished group fed 6% protein and a control group fed 25% protein. Newborns were selected from the two groups for injection with 14C-proline. Half of those injected were exposed to oxygen averaging 60 psig. Malnutrition impaired collagen synthesis in the lung as early as day 10 and in the heart at day 5. At day 20 and 30, pups from malnourished dams showed less severe convulsion than did the controls. Malnourished group displayed less adverse effect on lung and heart relative to body weight than did controls. Lung and heart collagen content in the malnourished group at days 15 and 10, respectively, were less than the controls. Between day 5 and day 20, OHP does not affect the metabolism of the lung and heart connective tissues, but it does by day 30. Malnutrition affects collagen metabolism of the heart earlier than it does the lung.

Animals↗

The effect of prenatal protein-energy malnutrition on the development of mandibles and long bones in newborn rats.

To evaluate the role of gestational protein-energy malnutrition on fetal hard-tissue growth and metabolism, we measured several variables in the growth centres of mandibles and long bones of newborn rats. Control pups and pups of malnourished dams had approximately the same extent of reduction in body-weight, mandibular weight and long-bone weight. The malnourished group had more cells in the mandible although cell size was the same as that of controls. In contrast, in the long bones, the malnourished group had fewer cells than did controls whereas cell size was unchanged. Calcium content was the same in long bones of both groups, but was less in the mandibles of pups from malnourished dams. Ca metabolism as measured by 45Ca uptake was unchanged in the long bones, but was increased in the mandibles of the malnourished group shortly after birth. Calcification patterns at birth in these bones correlated well with alkaline phosphatase (EC 3.1.3.1) activity. These findings indicate that the mandibles and long bones of offspring are affected differently by protein-energy malnutrition during the mother's gestation. Prenatal nutritional stress resulted in a disturbance of the pituitary-adrenal system. Increased adrenal corticosterone could possibly be related to the different observed changes in bone metabolism.

Animals↗

Influence of cholecystokinin on hypothalamic-stalk median-eminence-extract stimulation of ACTH output from isolated pituitary cells.

The influence of cholecystokinin 33 (CCK33) on CRF-like stimulation of ACTH output was tested in vitro using isolated pituitary cells. ACTH was assayed using isolated adrenal cell preparations. The CRF-like material was contained in a crude acetic-acid extract of hypothalamic stalk median eminence (HSME). CCK33, in doses of 1 U, 10(-3) U, and 10(-6) U/ml cell suspension had no influence on basal or ACTH-stimulated corticosterone output from isolated adrenal cells. Isolated pituitary cells responded in a dose-related fashion of HSME extract, however, the absolute response to a given dose of HSME extract varied according to the basal (non-stimulated) output of a particular cell preparation. CCK33, in the dose range tested, had no influence on basal ACTH output. In contrast, 10(-3) U/ml oc CCK33, which corresponds to a concentration of 8 X 10(-11) M, significantly inhibited the output of ACTH from isolated pituitary cells stimulated by 0.2 equivalents of HSME. Higher concentrations of CCK33 had a variable effect. We conclude that cholecystokinin may have a role in the regulation of HSME-stimulated ACTH output from the pituitary.

Adrenocorticotropic Hormone↗