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Biomedical subjects

D A Porter

Publications and source records attributed to D A Porter.

At least 55 records · Page 3Linked to original sources
PubMed1988

Magnetic resonance spectroscopy in vivo.

Nuclear magnetic resonance (NMR) has become an important non-invasive investigative technique in medicine and biology. The most recent development has been the ability to perform magnetic resonance spectroscopy (MRS) in selected regions within the human body. Such volumes can be selected by techniques which fall into the following broad categories: surface coil methods, surface coils with depth selection, volume selection and chemical shift mapping. The latter two methods use magnetic field gradients, present on magnetic resonance imaging systems, to select the volume. MRS can be used to measure phosphorus and proton metabolites and hence study tissue biochemistry in-vivo.

Brain Chemistry↗
PubMed1986

Dependence of GnRH action on Na+, K+, and Ca2+ in the frog, Rana pipiens, pituitary.

The roles of K+, Ca2+, and Na+ ions in the mechanism of gonadotropin releasing hormone (GnRH) action on frog (Rana pipiens) hemipituitaries were studied using an in vitro superfusion system. The effects of elevated K+ alone or in combination with Ca2+-depleted medium, tetrodotoxin (TTX), or with 100 ng/ml GnRH were examined. The involvement of K+ was also studied indirectly through the use of tetraethyl ammonium chloride (TEA). The importance of Ca2+ was established by the loss of responsiveness to GnRH in Ca2+-depleted medium, or in the presence of the Ca2+ competitor CoCl2. The absence of a major dependence of GnRH on Na+ was revealed by the continued gonadotropin secretion after addition of 1 microM TTX to medium containing GnRH or 36.3 mM KCl, or by replacement of NaCL with choline chloride. High (10 X normal) KCl (36.3 mM) stimulated gonadotropin--both LH and FSH--secretion, but the response was more gradual than for GnRH. The inclusion of TEA (to block K+ efflux) in medium with GnRH accentuated the effect of GnRH, and the effects of elevated (36.3 mM) KCl and 100 ng/ml GnRH (a relatively high dose) were additive. Responses to high K+, like GnRH, were abolished by removal of Ca2+ from the medium. Overall, the roles of K+, Ca2+, and Na+ ions in the mechanism of GnRH action are very similar between mammals and frogs; Ca2+ apparently serves a critical function in the mechanism of GnRH action, while Na+ appears not to be involved. K+ can induce gonadotropin secretion, but it is not clear that it plays a direct role in the mediation of the action of GnRH.

Animals↗
PubMed1986

The cellular basis of the calcium dependence of GnRH-stimulated gonadotropin release from frog, Rana pipiens, pituitaries.

An in vitro superfusion system was used in an attempt to identify the cellular systems involved in the Ca2+ dependence of gonadotropin-releasing hormone (GnRH) actions in the frog, Rana pipiens. Superfusion with 5 microM A23187 (a calcium ionophore) or phorbol myristate acetate (an analog of diacylglycerides) caused marked increases in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Exclusion of Ca2+ from the medium prevented the stimulatory effects of PMA. The potent stimulator of adenylate cyclase, forskolin, caused only slight stimulation of LH and FSH secretion, which was also prevented by removal of Ca2+. The cytoskeletal disruptive agents colchicine, nocodazole, and cytochalasin B, and the calmodulin inhibitors, trifluoperazine and pimozide, had no significant effects on the action of GnRH. Overall, these results indicate that the major mechanisms of Ca2+ involvement in the response to GnRH by the frog pituitary are similar to that of mammals, with the possible exceptions of lesser roles for calmodulin and the cytoskeleton in the frog. The study suggests that polyphosphatidyl-inositol-diacylglyceride metabolism may be critical in understanding the mechanism of GnRH action in frogs.

Animals↗
PubMed1986

Effects of temperature and mode of delivery on responses to gonadotropin-releasing hormone by superfused frog pituitaries.

An in vitro superfusion system was used to examine the effects of temperature on the responsiveness of frog, Rana pipiens, hemipituitaries to chronic superfusion with gonadotropin-releasing hormone (GnRH). The effects of pulsatile as opposed to continuous delivery of GnRH on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion were also studied at 30 degrees. Secretion of both gonadotropins (FSH and LH) increased significantly in a dose-dependent manner in response to a brief exposure to 0.1-1000 ng/ml (nM) GnRH at both 18 and 32 degrees, but the magnitude of response at each dose was temperature dependent. Moreover, the temporal pattern of the chronic response to a standard dose of GnRH (100 ng/ml) also varied markedly between 10 and 32 degrees: Hemipituitaries superfused at 10 or 18 degrees showed greatly attenuated responsiveness to GnRH after the first hour of GnRH treatment, whereas responsiveness was maintained or even continued to increase for many hours at higher temperatures. These temperature effects may be related to seasonal changes in reproductive activity. Pulsatile administration of GnRH was more effective in inducing elevated gonadotropin (GtH) secretion during the first few hours of superfusion, but continuous superfusion with GnRH was more effective at maintaining elevated GtH levels over long periods. The results support and extend previous studies by indicating that, unlike the situation in many mammals and birds, the frog pituitary is highly resistant to desensitization by even high doses of GnRH, and in fact, self-priming and maintained responsiveness to GnRH is better supported by chronic treatment than by pulsatile delivery of GnRH.

Animals↗
PubMed1986

Glucose feeding and exercise in trained rats: mechanisms for glycogen sparing.

This investigation studied the effect of an oral glucose feeding on glycogen sparing during exercise in non-glycogen-depleted and glycogen-depleted endurance-trained rats. The non-glycogen-depleted rats received via a stomach tube 2 ml of a 20% glucose solution labeled with [U-14C]glucose just prior to exercise (1 h at 25 m/min). Another group of rats ran for 40 min at higher intensity to deplete glycogen stores, after which they received the same glucose feeding and continued running for 1 h at 25 m/min. The initial 40-min run depleted glycogen in heart, skeletal muscle, and liver. In the non-glycogen-depleted rats the glucose feeding spared glycogen in the liver, primarily from the oxidation of blood-borne glucose in muscle. In the glycogen-depleted rats, muscle glycogen was repleted after the feeding, but sources other than the administered glucose also contributed to glycogen synthesis. The results suggest that glycogen depletion rather than the glucose feeding per se stimulates glycogen resynthesis in muscle during exercise in endurance-trained rats.

Animals↗
PubMed1985

Effects of gonadectomy and steroid treatment on plasma gonadotropins and the response of superfused pituitaries to gonadotropin-releasing hormone in the turtle Sternotherus odoratus.

Gonadectomized (gonadex) turtles, Sternotherus odoratus, had significantly elevated plasma FSH, but LH was less consistently affected. Estradiol (E2)-implants suppressed plasma FSH in gonadex females but not in males: testosterone (T) partially suppressed FSH in males. In contrast, E2-treatment markedly suppressed pituitary LH content and in vitro LH secretion in gonadex and intact turtles (inhibitory effects of E2 were less in intact than ovariectomized females). These steroid effects were relatively specific for gonadotropin; pituitary TSH content was not altered. In vitro, pituitary LH secretion responded to doses of GnRH greater than or equal to 1 ng/ml and LH output remained elevated for at least 3 hr of continuous superfusion with gonadotropin-releasing hormone (GnRH). In general, gonadectomy elevated pituitary responsiveness to GnRH while E2 and T suppressed this responsiveness; the effects of E2 are greater in gonadectomized than intact turtles. Thus, negative gonadal feedback appears to be involved in the secretion of gonadotropins in turtles, and steroidal actions may be partly due to suppression of pituitary hormone content and responsiveness to GnRH.

Animals↗
PubMed1985

In vivo and in vitro responses to gonadotropin releasing hormone in the turtle, Chrysemys picta, in relation to sex and reproductive stage.

In vivo and in vitro responsiveness to gonadotropin releasing hormone (GnRH) was studied in the turtle, Chrysemys picta, after manipulation of reproductive condition by temperature: Warm temperatures (28 degrees) induced testicular growth and ovarian regression compared to cold (17 degrees) treatment. Only males (and primarily from cold treatment) responded to GnRH injection (40 micrograms/100 g body wt intracardiac); correlated increases occurred in plasma LH and testosterone. Effects of GnRH (10 and 100 ng/ml) on LH and FSH secretion by hemipituitaries were studied in a superfusion system; tissues responded to between 0.1 and 1 ng/ml GnRH. Sex differences were evident in both acute and chronic effects of GnRH. Although both groups of females had significantly (sixfold) higher pituitary LH content, basal secretion rates of gonadotropins were similar, and LH and FSH secretion in males was more responsive to GnRH. Gonadotropin secretion rates by male glands showed high initial increments (approx four- to sevenfold) followed by an attenuation (especially LH) during 5 hr of GnRH superfusion. In contrast, tissues from warm-treated females showed a smaller initial response (approx twofold) followed by a progressive increase in output over time, and glands from cold-treated females did not respond to GnRH. Total LH secretion by superfused male hemiglands represented almost half the total LH recovered (secreted + stored); whereas, females secreted only 5% ("cold-treated") or 10% ("warm-treated") of total LH. Thus, the capacity of the pituitary to respond to GnRH is influenced by both sex and reproductive condition in the turtle. Secretion of both FSH and LH were similarly stimulated by GnRH, but thyrotropin (TSH) secretion was independent of GnRH.

Animals↗
PubMed1985

Pituitary responsiveness to superfused GnRH in two species of ranid frogs.

Dynamics of pituitary responsiveness to gonadotropin-releasing hormone (GnRH) as measured by LH and FSH secretion rates were examined for two species of ranid frogs in an in vitro superfusion system. The influence of sex was studied with juvenile bullfrogs, Rana catesbeiana, and responsiveness to long-term continuous superfusion with GnRH was examined in R. catesbeiana and R. pipiens. Female juvenile bullfrogs showed virtually no response to doses of GnRH up to 1000 ng/ml, whereas males responded to doses of GnRH as low as 10 ng/ml, and very large increments in LH and FSH were observed with 100 and 1000 ng/ml GnRH (responsiveness in the males was dependent on body size). Adult R. pipiens were more sensitive than bullfrogs to GnRH; 0.2 ng/ml GnRH was an effective dose. These data indicate that, relative to mammals, sensitivity to GnRH in frogs is higher than suggested by previous in vivo studies. As in mammals, "self-priming" in response to GnRH was evident; but unlike mammals, the "self-priming" occurred only after 7-12 hr of continuous superfusion with GnRH, and the R. pipiens glands were more resistant to desensitization during 48 hr of GnRH treatment. This study confirms that sex- and age-dependent differences in responsiveness to GnRH as well as "self-priming" found in previous in vivo studies are evidently dependent on properties of the anterior pituitary per se.

Aging↗
PubMed1985

LH secretion in response to gonadotropin releasing hormone (GnRH) by superfused pituitaries from two species of turtles.

A superfusion system was employed to study the dynamics of the responses of LH secretion to gonadotropin releasing hormone (GnRH) by anterior pituitary glands (quartered) from adult turtles, Pseudemys scripta and Chrysemys picta. Responsiveness was highly variable in both species, but in many cases, the tissues showed marked responses to relatively low doses (2-20 ng/ml) of GnRH. GnRH had no effect on LH secretion in five female P. scripta tested in the month of August, whereas it stimulated most glands tested in June and September; the few males tested were not as responsive as females in the same season. Female P. scripta invariably showed no or only very transient responses (less than 1 hr) to continuous GnRH superfusion, although glands recovered rapidly from this state of "desensitization" as evidenced by their ability to respond to subsequent stimuli. In some cases, pulsatile GnRH was effective in preventing this rapid desensitization. In contrast, glands from female C. picta were highly responsive in August. In March, they were similar to June P. scripta in showing a rapid desensitization to GnRH, whereas in August, the tissues of C. picta maintained full responsiveness to continuous GnRH for many hours. There was little evidence of GnRH "self-priming" in the turtles. The high individual variability in the magnitude of the response of LH to GnRH, the variable but often rapid desensitization to GnRH, as well as possible sexual, seasonal, and species differences in GnRH responsiveness may underlie the discrepancies previously observed among in vivo and in vitro studies in reptiles. However, the turtle is clearly not as unresponsive to mammalian GnRH as suggested by some previous studies.

Animals↗
PubMed1985

The effects of cycloheximide on in vitro response of Rana pipiens pituitaries to continuously superfused gonadotropin-releasing hormone.

An in vitro superfusion system was used to examine the effects of cycloheximide on the responsiveness of hemipituitaries from male Rana pipiens chronically treated with gonadotropin-releasing hormone (GnRH). Control hemipituitaries superfused with medium (DME) alone showed a rapid initial response to 100 ng/ml GnRH, and LH (luteinizing hormone) and FSH (follicle-stimulating hormone) levels remained above baseline throughout up to 13 h of treatment with GnRH. Subsequent to a 2-h rinse with DME alone following the initial treatment with GnRH, these control tissues showed a highly augmented increase in gonadotropin secretion in response to a final hour of GnRH superfusion, suggesting self-priming with as little as 5 h of initial GnRH treatment. Hemipituitaries treated with 71 microM cycloheximide showed a similar rapid initial response to 100 ng/ml GnRH, but levels declined to less than in control tissues within 3 h. Moreover, these tissues exhibited only slight responses when challenged with GnRH a second time. There were also no significant differences in response to GnRH by glands pretreated with cycloheximide for either 3 or 9 h. These results indicate the presence of a rapidly releasable pool of gonadotropin responsible for the initial response to GnRH that has minimal requirements for protein synthesis, and a second pool dependent upon protein synthesis that is involved in the maintenance of elevated gonadotropin secretion in response to chronically superfused GnRH, and for self-priming.

Animals↗
PubMed1976

Comparison of antibody responses and reactivity of "Alice" and WRL 105 strain live influenza vaccines.

Groups of 45 adult volunteers were vaccinated intranasally with a single dose of either "Alice" or WRL 105 strain live influenza vaccines. Seroconversion rates against A/Scotland/840/74 were significantly greater following administration of WRL 105 but seroconversion rates against A/England/42/72, A/Port Chalmers/1/73, A/Finland/4/74, A/Victoria/3/75, and A/England/864/75 did not differ significantly between the two vaccines. Poor antibody responses were elicited by both "Alice" and WRL 105 strains against A/Victoria/3/75 and A/England/864/75. No severe reactions followed the administration of either vaccine.

Administration, Intranasal↗
PubMedDate not supplied

Visibility of phospholipids in 31P NMR spectra of human breast tumours in vivo.

The aims of this study were two-fold: to characterize the in vivo 31P NMR spectrum of human breast tumours by identifying the metabolites contributing to each peak; and to demonstrate changes in the detectability of the phosphodiester (PDE) peak at varying field strengths. This was achieved by obtaining 31P spectra from 23 patients in vivo at 1.5 T and also of 11 perchloric acid (PCA) extracts and 3 chloroform-methanol (CM) extracts of tumour biopsy samples at 9.4 T. In spectra acquired in vivo the percentage areas for each peak were: phosphomenoester (PME), 15%; Pi, 11%; PDE 35%; phosphocreatine, 5%; gamma-NTP, 11%; alpha-NTP, 11% and beta-NTP, 12% of the total spectral area. PCA extracts showed the PME peak to be greater than 70% phosphorylethanolamine whilst the PDE peak included almost equal proportions of glycerophosphorylethanolamine and glycerophosphorylcholine. CM extracts of tumours revealed additional metabolites in the PDE region suggesting that the large PDE peak observed in vivo could arise mainly from phospholipids. Spectra of human breast tumour xenografts examined in vivo at both 1.9 T and 9.4 T confirmed that the presence of a large PDE peak in vivo was a function of field strength. Further experiments with microsomal membranes from rat mammary tumours at 1.5 and 9.4 T demonstrated that phospholipids are more clearly visible at the lower field strength due to a substantial decrease in linewidth.

Animals↗
PubMedDate not supplied

Experimental characterization of the ISIS technique for volume selected NMR spectroscopy.

As clinical applications of MRS grow in number and complexity, there is a need for standardized methods for characterizing the performance of volume selection techniques. The results are presented of a thorough evaluation of a particular implementation of ISIS performed using a procedure which forms the basis of the method adopted by the European Community Concerted Action on MRS and MRI. We have found that ISIS localization is optimal when the volume of interest is slightly smaller than the region we wish to study. Contamination with extraneous signal has little T1 dependence so long as TR greater than T1 and the detection pulse angle is 90 degrees. However, a poorly optimized detection pulse results in T1-weighted contamination unless TR greater than 3T1. In the clinical context, this corresponds to a different degree of contamination for each peak in the spectrum. Adiabatic detection pulses were used in an attempt to overcome this problem without resorting to unacceptable TR values, but these were found to function less well than properly optimized rectangular pulses, even if the power was increased above the level determined by the system for B1 insensitivity. These detailed results pertain only to our system, but illustrate the importance of performing similar measurements as part of clinical spectroscopy programmes at other centres.

Evaluation Studies as Topic↗
PubMedDate not supplied

Anterior cruciate ligament-medial collateral ligament injury: nonoperative management of medial collateral ligament tears with anterior cruciate ligament reconstruction. A preliminary report.

We present the results of a series of patients who had nonoperative management of the medial collateral ligament with anterior cruciate ligament reconstruction. From February 1983 through December 1989, 84 of 90 consecutive patients were available for followup (minimum, 1 year; mean, 3.1 years) with a combined anterior cruciate ligament-medial collateral ligament injury (anterior cruciate ligament rupture and medial collateral ligament tear) received surgical management by the same physician. The last 68 of these 84 patients who met the inclusion criteria underwent patellar tendon graft for anterior cruciate ligament reconstruction, with concomitant nonoperative management of medial collateral ligament tears. Follow-up evaluation consisted of physical examination for medial laxity, range of motion, and isokinetic and KT-1000 testing. Brace use and postoperative level of competition were also recorded. In addition, the patients completed a subjective assessment questionnaire rating pain, swelling, and stability. They also rated overall activity level, and any changes in their ability to do the activities tested: walk, climb stairs, run, jump, or twist. Our results indicate that proper reconstruction of the anterior cruciate ligament, in conjunction with nonoperative management of tears of the medial collateral ligament in combined anterior cruciate ligament-medial collateral ligament injuries, can given excellent stability and good to excellent functional outcome in patients with combined anterior cruciate ligament-medial collateral ligament injuries.

Adolescent↗