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D C Johnson

Publications and source records attributed to D C Johnson.

At least 181 records · Page 10Linked to original sources
PubMed1986

Pharmacology of the bipyridines: amrinone and milrinone.

The cardiovascular bipyridines amrinone and milrinone are positive inotropic agents with vasodilator properties. When their effects on the heart and circulation were studied in both isolated cardiac tissues and anesthetized animals, milrinone was found to be 30 times more potent than amrinone. The inotropic response of isolated atria and papillary muscles to the bipyridines was characterized by increases in isometric tension and in the rates of tension development and relaxation. In the anesthetized dog, amrinone (1.0 mg/kg iv) and milrinone (0.03 mg/kg iv) caused significant increases in left ventricular dP/dtmax, cardiac output, and heart rate, significant decreases in pulmonary arterial pressure, and no change in systemic blood pressure. Studies to elucidate the mechanism(s) of action of the bipyridines indicated that Ca++ and cyclic AMP (cAMP) play important roles. The inotropic response to milrinone was modified by changes in the rate of stimulation and the concentration of extracellular Ca++ and by depolarization with high K+ or pretreatment with a calcium-channel blocker. Reduction of the extracellular Na+ concentration of 75% of normal potentiated the inotropic response of papillary muscles to low concentrations of milrinone, suggesting possible activation of the Na+-Ca++ exchange mechanism. These results suggest that milrinone may stimulate the influx of Ca++ into the cardiac cell. The bipyridines are phosphodiesterase inhibitors that increase cardiac cAMP levels. However, a time-course analysis of the changes in cAMP levels during the inotropic response to the bipyridines indicated that the increase in isometric tension development preceded the increase in cAMP. Our data suggest that more than one mechanism may be involved in the initiation and maintenance of the inotropic response to the bipyridines.

Acetylcholine↗
PubMed1986

Acute and long term effect of nifedipine on pulmonary hypertension secondary to chronic obstructive airways disease.

To determine whether Nifedipine reduces pulmonary artery pressure and pulmonary vascular resistance in patients with hypoxic pulmonary hypertension, we have studied ten clinically stable patients with chronic obstructive airways disease following acute administration of sublingual Nifedipine 20 mg and also after three months long term treatment with Nifedipine tablets 20mg bd. In the acute study, Nifedipine significantly raised mean pulmonary artery pressure from 30.32 +/- 13.07 mm Hg to 34.15 +/- 14.33 mm Hg (p less than 0.001) and pulmonary wedge pressure from 6.15 +/- 5.09 mm Hg to 7.6 +/- 3.39 mm Hg (p less than 0.1). There was a significant fall in mean systematic artery pressure from 99.06 +/- 12.05 mm Hg to 89.47 +/- 10.04 mm Hg (p less than 0.005) and a rise in heart rate from 79 +/- 9.7 beats/minute to 85.45 +/- 13.46 beats/minute (p less than 0.5). There was a significant change in cardiac index from 2.96 +/- 0.76 l/min/m2 to 3.2 +/- 0.51 l/min/m2 p(less than 0.1). There was no statistically significant change in pulmonary vascular resistance from 5.06 +/- 3.45 mm Hg/l/min to 4.92 +/- 3.10 mm Hg/l/min. In the long term study, no statistically significant differences over the base line values were found in measurements of mean pulmonary artery and pulmonary wedge pressures, mean systemic artery pressure, cardiac index and PO2. There was a greater fall in pulmonary vascular resistance in comparison with the acute study. The pulmonary vascular resistance fell from 5.06 +/- 3.45 mm Hg/l/min to 4.24 +/- 2.31 mm Hg/l/min but did not achieve statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Shattered silence.

Explore the source record for details and available documents.

Communication↗
PubMed1985

Altered hypothalamic-pituitary function in the adult female rat with streptozotocin-induced diabetes.

Infertility associated with anovulation and loss of regular oestrous cyclicity is a consequence of diabetes mellitus in the rat. In an attempt to define loci of altered function, studies were undertaken to examine various aspects of hypothalamic-pituitary function in rats treated with streptozotocin. Medial basal hypothalamic fragments from adult female diabetic rats contained the same amount of gonadotrophin-releasing hormone but, with depolarization, released slightly but insignificantly (p greater than 0.05) more than did those from control animals. Furthermore, release of luteinizing hormone from pituitaries exposed to hypothalamic gonadotrophin-releasing hormone was not altered by diabetes. Removal of the negative feedback effect of gonadal steroids upon the hypothalamic-pituitary axis produced an increase in luteinizing hormone and follicle stimulating hormone concentrations in the serum of normal rats within 6h (p less than 0.05), whereas 24h were required for similar increases in diabetic rats. However, the same concentrations of gonadotrophins were found in diabetic and control animals 120 h after ovariectomy. The inhibitory action of oestradiol benzoate on the secretion of gonadotrophins was more pronounced in ovariectomized diabetic than in control rats. A 74% depression in serum luteinizing hormone (p less than 0.01) was produced by 0.5 microgram oestradiol benzoate per day in diabetic rats, while 5 micrograms was required in control animals. Similar reductions in follicle stimulating hormone concentrations (50%, p less than 0.05) were obtained by injecting 5 micrograms of the oestrogen into diabetic or 50 micrograms into control rats. Increases in serum prolactin were greater in the control animals however.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Inhibition by potential metabolic inhibitors of in vitro adipose tissue lipogenesis.

To study the pathway of lactate utilization as a carbon source for fatty acid synthesis, the effect of (-)-hydroxycitrate, agaric acid, sodium oxamate, 2-n-butyl malonate and alpha-cyano-4-hydroxycinnamate on the rate of in vitro conversion of lactate, acetate and glucose to fatty acids was measured in bovine and rat adipose tissues. Sodium oxamate and hydroxycitrate caused less fatty acid to be synthesized from lactate in bovine adipose tissue. Hydroxycitrate depressed fatty acid synthesis from glucose in rat adipose tissue. alpha-Cyano-4-hydroxycinnamate was an effective inhibitor of lipogenesis from all substrates and may act as a specific inhibitor in adipose tissue. Although the inhibitors were absorbed poorly into adipocytes, the results indicate that conversion of lactate to fatty acids probably occurs by way of the citrate cleavage pathway.

Acetates↗
PubMed1985

Curative surgery for atrioventricular junctional ("AV nodal") reentrant tachycardia.

A new surgical approach was studied prospectively in 10 consecutive patients with atrioventricular (AV) junctional reentrant tachycardia. The aim was to abolish tachycardia yet preserve normal AV conduction. On the basis of electrophysiologic study before operation, patients were classified as type A (ventriculoatrial [VA] intervals during tachycardia less than or equal to 40 ms) (seven patients) or type B (VA intervals greater than 40 ms) (three patients). Dual AV junctional pathways were demonstrable with single extrastimulus testing in seven patients before operation. Endocardial mapping during tachycardia at surgery revealed earliest atrial activation anteromedial to the AV node in type A patients and posterior to the node in the type B patients. The perinodal atrium in the region of earliest atrial activation during tachycardia was carefully disconnected from the AV node. After operation, AV junctional reentrant tachycardia was not inducible at comprehensive electrophysiologic study in any patient, and no clinical recurrences have occurred during a follow-up period of 2 to 14 months (mean 8 +/- 4). Normal AV conduction was preserved in all cases. Anterograde slow AV junctional pathway conduction was abolished in five of seven cases. Retrograde His to atrium conduction time was prolonged in type A patients but the capacity for retrograde VA conduction remained excellent. Retrograde His to atrium conduction was interrupted or severely compromised in the type B patients. These data show that there are at least two types of AV junctional reentry. Perinodal atrium appears to be part of the reentrant circuit in human AV junctional reentry. Although the most consistent effect of surgery was on the retrograde limb of the circuit, anterograde slow pathway conduction was also modified. AV junctional reentry is surgically curable with a high success rate.

Adult↗
PubMed1985

Intracellular transport of herpes simplex virus gD occurs more rapidly in uninfected cells than in infected cells.

A mouse L cell line which expresses the herpex simplex virus type 1 immediate-early polypeptides ICP4 and ICP47 was cotransfected with a cloned copy of the BglII L fragment of herpes simplex virus type 2, which includes the gene for gD, and the plasmid pSV2neo, which contains the aminoglycosyl 3'-phosphotransferase (agpt) gene conferring resistance to the antibiotic G418. A G418-resistant transformed cell line was isolated which expressed herpes simplex virus type 2 gD at higher levels than were found in infected cells. The intracellular transport and processing of gD was compared in transformed and infected cells. In the transformed Z4/6 cells gD was rapidly processed and transported to the cell surface; in contrast, the processing and cell surface appearance of gD in infected parental Z4 cells occurred at a much slower rate, and gD accumulated in nuclear membrane to a greater extent. Thus, the movement of HSV-2 gD to the cell surface in infected cells is retarded as viral glycoproteins accumulate in the nuclear envelope, probably because they interact with other viral structural components.

Animals↗
PubMed1985

Differences between CSF and plasma Na+ and K+ activities and concentrations.

[Na+] and [K+] determined by ion-selective electrodes (ISE) by direct potentiometric determination were compared with those obtained by flame photometry in plasma and in cisternal cerebrospinal fluid (CSF) obtained from pentobarbital-anesthetized dogs. Comparisons of pre- and postanesthesia values showed no change in plasma [Na+] but a 5% fall in plasma [K+]. CSF and plasma Na+ activities were identical, indicating that Na+ does not contribute to the potential difference between them. CSF K+ activity was 74% of that in plasma. The CSF-to-plasma molar and molal ratios differed from the activity (ISE) ratios. Concentrations of Na+ and K+ were also determined in an electrolyte solution and in the same solution with albumin added. Flame values differed from ISE values in plasma, CSF, and solutions. Albumin lowered flame values to a greater extent than ISE values. Bicarbonate lowered ISE values. ISE ratios, which equal activity ratios, rather than molar or molal ratios should be used in thermodynamic equilibrium equations, whereas molar concentrations should be used in electroneutrality equations or in determination of the strong ion difference.

Anesthesia↗
PubMed1985

Catechol oestrogen induced initiation of implantation in the delayed implanting rat.

In the rat oestrogen is essential for induction of implantation in a progesterone primed uterus. The ability of the catechol oestrogens, 4-hydroxy-oestradiol (4-OH-E2) and 2-hydroxy-oestradiol (2-OH-E2) to initiate the implantation process (blue reaction, indicative of increased endometrial capillary permeability at the location of the blastocyst) in hypophysectomized delayed implanting rats was compared to that of oestradiol-17 beta (E2). Delayed implantation was maintained by daily administration of 2 mg of progesterone. A single sc injection of 100 ng of E2 or 400 ng of 4-OH-E2 consistently initiated implantation in all animals. When delivered sc via osmotic minipumps at a constant release rate of 10 ng/microliters/h, implantation of a full complement of embryos was obtained with E2 given for 6 or 24 h. This dose 4-OH-E2 was ineffective when administered for 24 h. However, 25 ng/microliters/h for 24 h was effective. When the dose was increased to 50 ng/microliters/h implantation was evident in the majority of animals exposed to the hormone for 6 or 8 h; all animals implanted when this dose was given for 24 h. In contrast, 2-OH-E2 given at 50 ng/microliters/h for 24 h was totally ineffective. When the dose of the latter steroid was raised to 200 ng/microliters/h implantation was achieved in half of the animals when exposure was 24 h. The results suggest that when administered systemically, 4-OH-E2 is less potent than E2, but more potent than 2-OH-E2, for initiating implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Evidence for pituitary regulation of placental lactogen in the rat.

The present studies examined whether the pituitary hormones, particularly prolactin, have any role in the regulation of rat placental lactogen (rPL) secretion. Total rPL was measured using a lymphoma cell bioassay. Hypophysectomy on day 13 of pregnancy increased total serum rPL levels above those of intact control rats and delayed for 3 days the decline in rPL usually seen by day 14. To test the effect of early hypophysectomy on rPL secretion, a delayed implantation model was used. Hypophysectomy was carried out on day 3, progesterone (2 mg) was given daily until day 8 and oestrone (1.0 micrograms) was given on day 8. This initiated implantation on day 9, which is 4 days later than normal. Rats hypophysectomized on day 3 had high serum levels of rPL (10-13 mg/l) 7 days after initiation of implantation compared with control values of 2-3 mg/l, and these levels remained raised for the duration of the experiment. Termination of maintenance injections of steroids did not affect the high levels of rPL for several days, even though there was fetal and placental resorption. When a pair of anterior pituitaries was transplanted under the kidney capsule on day 13 (day 9 of development) of rats hypophysectomized on day 3, serum rPL levels still increased for the next 3 days. However, unlike similarly treated rats not receiving transplants, rPL levels fell rapidly thereafter and were only 5% of those in control animals 1 week later.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Ovarian C17,20-lyase: changes in intact and hypophysectomized immature rats treated with pregnant mare's serum gonadotropin.

The steroid C17,20-lyase activity of immature rat ovarian microsomal (105,000 g pellet), mitochondrial (10,000 g pellet) and combined fractions was measured using progesterone and 17-hydroxyprogesterone as substrates. Steroid 17 alpha-hydroxylase was measured, using progesterone as substrate, in some of the preparations for comparison. With progesterone about 3.5 times more product (acetic acid) was formed than with 17-hydroxyprogesterone as substrate. The half-time for lyase activity following hypophysectomy was 51.8 h, while that for 17 alpha-hydroxylase was 51.3 h. Following an intravenous injection of 20 iu of pregnant mare's serum gonadotropin (PMS) into immature hypophysectomized rats lyase activity decreased for 12 h followed by recovery during the next 12 h with a rapid increase between 24 and 72 h. In contrast, a subcutaneous injection of the same dose produced an initial rise in activity with a decline between 12 and 24 h, followed by a second large increase. In intact animals injection (s.c.) of PMS produced an initial fall in lyase activity followed by an increase beginning 12 h later. A dramatic decrease in activity occurred between 48 and 72 h concomitant with ovulation; hypophysectomy at 48 h not only prevented the decrease, but produced an increase in activity. The changes in ovarian C17,20-lyase activity following administration of PMS mimic those of 17 alpha-hydroxylase.

Aldehyde-Lyases↗
PubMed1984

Effect of furosemide on cerebrospinal fluid composition.

Electrolyte composition of the cerebral spinal fluid (CSF) is important in central respiratory drive. The relationship between [Cl-] and [HCO3-] is of particular interest in maintenance of electrolyte balance. Therefore, the effect of furosemide, an inhibitor of sodium-coupled chloride transport, on CSF electrolyte homeostasis was studied under conditions of normocapnia and hypercapnia in anesthetized dogs. The drug was given intravenously (IV) or in the lateral cerebral ventricles (CV). With normocapnia, there was no change in CSF or arterial PCO2, pH, [K+], [Cl-], or [HCO3-], while CSF [NA+] decreased 1.7 mM in dogs receiving IV furosemide. With 5% CO2 breathing and IV furosemide, CSF PCO2, pH, [K+], [Cl-], and [HCO3-] changed as has been reported for 5% CO2 breathing alone. 5% CO2 and CV furosemide, however, led to a greater reduction in CSF [Cl-] and no change in CSF [HCO3-]. Thus CV furosemide alters the CSF [Cl-] and [HCO3-] in hypercapnia, suggesting that sodium-coupled chloride transport plays a role in regulation of CSF acid-base homeostasis.

Acid-Base Equilibrium↗
PubMed1984

Studies on the temporal pattern of prostaglandin synthesis in the uterus of the delayed implanting rat with or without implantation inducing stimuli.

The model of delayed implantation produced by injection of progesterone (P4) following hypophysectomy on day 3 of pregnancy, was used to study the temporal relationship between phospholipase A2 (PLA2) activity and endogenous concentrations and/or in vitro production of prostaglandins (PGs) in the rat uterus during the early phase of implantation. No definitive correlation between the endogenous concentration of uterine PGs and their in vitro production, or PLA2 activity, was found following various treatments. However, an interesting interaction between various treatments and PLA2 activity, as well as PG production, was evident within 0.5 h-4 h. The unaltered PLA2 activity and PG production in the uterus at 0.5 h and 4 h after the last injection of P4 only suggest that PLA2 is probably the limiting step in PG synthesis in the P4 dominated uterus. On the other hand, the depressed uterine PG production at 0.5 h, in the face of unaltered PLA2 activity, in P4-primed rats injected with an optimal dose of estradiol-17 beta (E2: 20 ng/rat, i.v.) suggests a reduction in PG synthetase activity with estrogen. Because PLA2 activity remained unchanged, the stimulation in PGE, and to some extent PGF, production at 0.5 h following superimposition of histamine on the E2 treatment appears to be mediated via stimulation of PG synthetase. The increase in PGE and PGF production at 4 h as compared to 0.5 h following E2 injection was accompanied by increased PLA2 activity. However, PGF production did not exceed that obtained with only P4. Addition of histamine to the P4 and E2 treatment potentiated the stimulation of PG production at 4 h without further elevation in PLA2 activity. A suboptimal dose of E2 (10 ng/rat, i.v.) failed to increase PLA2 activity and PG production, compared to those obtained with 20 ng/rat of E2. However, coadministration of histamine with the low dose of E2 increased PG production to the level found with the optimal dose of E2; this was achieved without a significant change in PLA2 activity. On the other hand, histamine did not reverse the inhibitory effect of dexamethasone on E2 stimulation of PLA2 activity and PG production. Taken together these results suggest that histamine induced potentiation of PG production in P4 and E2 treated rats is probably mediated via activation of PG synthetase activity. PLA2 activity was increased significantly at 8 h after the last injection of P4. However, this increase in activity was reflected in increased PGE, but not PGF production.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

The in vitro and in vivo effect of estradiol upon the 17 alpha-hydroxylase and C17,20-lyase activity in the ovaries of immature hypophysectomized rats.

The effect of a single injection of estradiol benzoate upon the activity of 17 alpha-hydroxylase and C17,20-lyase in the ovaries of hypophysectomized immature rats was investigated. Tritiated H2O from 17 alpha-[3H]progesterone and 14CH3COOH from 21-[14C]progesterone were the products measured to evaluate the hydroxylase and lyase activities respectively. Estradiol (E2) had no direct effect upon the activity of the enzymes in vitro even when present at twice the concentration of the substrate. However, when given in vivo, E2 reduced the activity of both enzymes. The ratio of the activities remained constant supporting the contention that both enzyme activities reside in one cytochrome P-450. Cycloheximide attenuated, but did not prevent, the reduction obtained with estrogen. Enzyme activities were reduced by E2 to a slightly lesser degree when the ovaries had been exposed in vivo to exogenous gonadotropin for 72 h. The results indicate that 17 alpha-hydroxylase and C17,20-lyase activities decrease when large doses of E2 are administered in vivo, that this effect is not directly on the enzymes, and that at least a part of this effect involves macromolecular synthesis.

Aldehyde-Lyases↗
PubMed1984

Evidence for translational regulation of herpes simplex virus type 1 gD expression.

We compared the rates of synthesis of herpes simplex virus type 1 glycoproteins C and D and quantitated the accumulation of translatable mRNA for each glycoprotein at various times after infection. The rate of synthesis of gD increased sharply early in the infection, peaked by 4 to 6 h after infection, and declined late in the infection. In contrast, the rate of synthesis of gC increased steadily until at least 15 h after infection. The levels of mRNA for both of these glycoproteins, as detected by hybridization and by translation in vitro, continued to increase until at least 15 or 16 h after infection. Synthesis of both gC and gD and their respective mRNAs was found to be sensitive to inhibition of viral DNA replication with phosphonoacetic acid. The finding that reduced amounts of gD were synthesized late in the replicative cycle, whereas gD mRNA continued to accumulate in the cytoplasm, argues that the synthesis of gD is regulated, in part, at the level of translation.

Animals↗