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Biomedical subjects

D A Porter

Publications and source records attributed to D A Porter.

At least 19 recordsLinked to original sources

Familial periodic cerebellar ataxia: a problem of cerebellar intracellular pH homeostasis.

Six affected members of two families with familial periodic cerebellar ataxia were relieved of their symptoms with oral acetazolamide. Phosphorus 31 (31P) nuclear magnetic resonance spectroscopy showed abnormal intracellular pH levels in the cerebellum of all subjects when they were not treated. These levels returned to normal with treatment. Cerebral pH values were also measured in one family and were normal before and after treatment. An additional 3 patients with similar attacks, but without a family history, had normal untreated pH values in the cerebellum and cerebrum.

Acetazolamide

Nucleotide sequence of the cDNA encoding the common alpha subunit of the chicken pituitary glycoprotein hormones.

Recombinant cDNA clones that encode the alpha subunit of the chicken pituitary glycoprotein hormones were isolated from a pituitary library. The longer of the two cDNA clones that were sequenced was 754 bp in length. It contained 81 nucleotides of the 5'-untranslated region (UTR), an open-reading frame of 360 bp that encoded a 24 amino acid leader polypeptide sequence as well as the 96 amino acid mature alpha subunit, and 268 nucleotides of the 3'-UTR, followed by a 45 bp poly(A) tract. There was 69-79% homology between the nucleotide sequence of the coding region for the chicken and mammalian alpha-subunit cDNAs. Northern blot analysis revealed that the steady-state levels of an approximately 800 bp alpha-subunit specific transcript increased quantitatively when dispersed chicken pituitary glands were treated in culture with chicken gonadotrophin-releasing hormone-I.

Amino Acid Sequence

D-value determinations are an inappropriate measure of disinfecting activity of common contact lens disinfecting solutions.

Determination of a D value for specific test organisms is a component of the efficacy evaluation of new contact lens disinfecting solutions. This parameter is commonly defined as the time required for the number of surviving microorganisms to decrease 1 logarithmic unit. The assumption made in establishing a D value is that the rate of kill exhibits first-order kinetics under the specified conditions. Such exponential kill rates are seen with thermal contact lens disinfection system. A comparison of the death rate kinetics for a variety of chemical contact lens disinfecting solutions was undertaken to ascertain the suitability of D-value determination for these chemical disinfectants. The active agents of these different solutions included hydrogen peroxide, thimerosal, chlorhexidine, tris(2-hydroxyethyl)tallow ammonium chloride, thimerosal, polyaminopropyl biguanide, and polyquaternium-1. The solutions were challenged with 10(6) CFU of either Pseudomonas aeruginosa, Serratia marcescens, or Staphylococcus hominis per ml, and survival rate was determined. This study clearly demonstrates the nonlinear nature of the inactivation curves for most contact lens chemical disinfecting solutions for the challenge organisms. D-value determination is, therefore, an inappropriate method of reporting the biocidal activity of these solutions.

Contact Lenses

Low-velocity knee dislocation.

Complete knee dislocation is an uncommon but potentially devastating injury with a reported high rate of neurovascular injury. Treatment of this ligamentous injury is controversial. The operative (repair of all ligaments) and nonoperative management of ligament injuries appears to result in a stiff knee (decreased range of motion [ROM]), and/or a significant incidence of clinical instability and pain. We report our data on low-velocity knee dislocations and present a treatment plan of noninvasive assessment of the vascular status, a stabilizing procedure centered on posterior cruciate ligament reconstruction (PCL) and an aggressive rehabilitation program that can result in improved ROM, acceptable stability, and a more optimal functional outcome.

Adolescent

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

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

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

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

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

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

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

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

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

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

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