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C R Ward

Publications and source records attributed to C R Ward.

33 records · Page 2Linked to original sources

Effect of intrathecal morphine on the fate of glucose. Comparison with effects of insulin and xanthan gum in mice.

The hypoglycemic effect of morphine (40 micrograms) injected intrathecally (i.t.) was studied with regard to disposition of i.v. [14C]glucose and [3H]2-deoxyglucose and was compared with the effects of two other hypoglycemic agents, insulin (1 IU/kg, s.c.) and xanthan gum (50 mg/kg, i.p.). Mice given i.t. morphine or s.c. insulin exhaled a greater amount of 14CO2 from i.v. [14C]glucose than did control mice given i.t. saline, whereas there was less 14CO2 expiration in xanthan-treated mice. In morphine-treated mice there was less 14C in liver, brain and blood, and more 3H in kidney and hindleg muscle than in control mice. Insulin-treated mice had more 14C in muscle, less 14C in liver, brain, kidney and blood, and less 3H in liver and blood. In xanthan-treated mice, levels of both radiolabels were higher in liver, brain and kidney. Much lower glycogen content in muscle and depletion of liver glycogen occurred in morphine-treated mice, compared with control mice. Spinal transection completely inhibited the hypoglycemic effect of morphine, whereas adrenalectomy caused no inhibition. Morphine, insulin and xanthan appear to be acting by different mechanisms, although the hypoglycemic effects of both morphine and insulin appear to be due largely to an increased glucose uptake by muscle.

Animals↗

Molecular events mediating sperm activation.

Fertilization is a unique event in the life of an organism and results from requisite and reciprocal cell-induced sperm and egg activation events mediated by unique cellular and environmental cues associated with either the gametes or the reproductive tract/environment. Sperm interaction with the female reproductive tract/environment and sperm-egg interaction both at a distance and in close proximity represent a series of integrated processes designed to deliver sperm with optimal fertilizing potential to the site of fertilization. The idea that sperm and eggs "communicate" prior to fertilization, and that these communicative processes are requisite for successful fertilization, has been proposed for nearly a century. Recent studies have revealed that many aspects of gamete activation prior and subsequent to fertilization have similarities to intercellular and intracellular signaling systems utilized by somatic cells. The nature of these signaling systems is now being elucidated at the molecular level in both vertebrate and nonvertebrate systems and has revealed some unique aspects of communication and transmembrane signaling between gametes. This review will consider the mechanisms by which eggs communicate with sperm to initiate sperm activation events that are essential for fertilization. It will focus particularly on some of the most recent work surrounding these issues, and new directions and questions that are relevant to this most highly specialized interaction between gametes will be discussed.

Acrosome↗

Activation of a Gi protein in mouse sperm membranes by solubilized proteins of the zona pellucida, the egg's extracellular matrix.

Zona pellucida (ZP)-induced acrosomal exocytosis in mammalian spermatozoa is thought to be mediated by signal transduction cascades similar to those found in hormonally responsive cells. In order to characterize this process further, we have examined the role of GTP-binding regulatory proteins (G proteins) in coupling sperm-ZP interaction to intracellular second messenger systems in mouse sperm. An in vitro signal transduction assay was developed to assess ZP-G protein dynamics in sperm membrane preparations. Guanosine 5'-3-O-(thio)triphosphate (GTP gamma S), a poorly hydrolyzable analogue of GTP, bound to these membranes in a specific and concentration-dependent fashion which reached saturation at 100 nM. Incubation of the membrane preparations with heat-solubilized ZP resulted in a significant increase in specific GTP gamma S binding in a concentration-dependent fashion with a half-maximal response at 1.25-2 ZP/microliters. Solubilized ZP also caused a significant increase in high affinity GTPase activity in the membranes over basal levels. Mastoparan increased specific GTP gamma S binding to the sperm membranes and stimulated high-affinity membrane GTPase activity to levels consistently greater than that seen with the solubilized ZP. Mastoparan, together with solubilized ZP, gave the same level of stimulation of GTP gamma S binding as mastoparan alone. Pertussis toxin completely inhibited the ZP-stimulated GTP gamma S binding, but only decreased mastoparan-stimulated GTP gamma S binding by 70-80%. Purified ZP3, the ZP component which possesses quantitatively all of the acrosomal exocytosis-inducing activity of the intact ZP, stimulated GTP gamma S binding to the same level as solubilized ZP; ZP1 and ZP2 did not stimulate GTP gamma S binding. ZP from fertilized eggs (ZPf), which does not possess acrosome reaction-inducing activity, also failed to stimulate GTP gamma S binding to sperm membranes. These data demonstrate the direct activation of a Gi protein in sperm membrane preparations in response to the ZP glycoprotein, ZP3, that induces the acrosome reaction. These data imply that Gi protein activation is an early event in the signal sequence leading to sperm acrosomal exocytosis.

Acrosome↗

Activation of a G protein in mouse sperm by the zona pellucida, an egg-associated extracellular matrix.

Mammalian sperm possess a guanine nucleotide-binding regulatory protein (G protein), with properties similar to Gi, that appears to be involved in the signal transduction pathway required for zona pellucida (ZP)-mediated acrosomal exocytosis. Mouse sperm treated with pertussis toxin (PT), a toxin that functionally inactivates Gi proteins, bind to the ZP of mouse eggs but are inhibited from undergoing acrosomal exocytosis. We have measured high-affinity GTPase activity and GTP gamma [35S] binding in mouse sperm homogenates incubated in the absence and presence of ZP glycoproteins isolated from either ovulated eggs or from ovarian homogenates to determine whether this extracellular matrix can activate the sperm-associated Gi protein. An increase in GTP hydrolysis (approximately 50% over basal activity) and GTP gamma [35S] binding (approximately 25-60% over basal activity) is observed when sperm homogenates are incubated in the presence of solubilized ZP glycoproteins, and the increase in GTPase activity is dependent on the concentration of ZP added to the homogenates. Accompanying this increase is a reduction in the ability of PT to catalyze in vitro [32P]ADP-ribosylation of a Mr = 41,000 sperm Gi protein, suggesting that the increase in GTPase activity and GTP gamma [35S] binding is associated with the activation of a PT-sensitive sperm G protein(s). The ability of the ZP to stimulate high-affinity GTPase activity in these homogenates appears to be dependent on the capacitation state of the sperm from which the homogenates are prepared. These data suggest that a component(s) of the ZP may function in a manner similar to that of other ligands by binding to a sperm surface-associated receptor and subsequently activating a G protein coupled to an intracellular signal transduction cascade(s) required for induction of acrosomal exocytosis.

Animals↗

Antagonism of the morphine-induced locomotor activation of mice by fructose: comparison with other opiates and sugars, and sugar effects on brain morphine.

The mouse locomotor activation test of opiate action in a 2+2 dose parallel line assay was used in a repeated testing paradigm to determine the test, opiate and hexose specificities of a previously reported antagonism of morphine-induced antinocociception by hyperglycemia. In opiate specificity studies, fructose (5 g/kg, i.p.) significantly reduced the potency ratio for morphine and methadone, but not for levorphanol, meperidine or phenazocine when intragroup comparisons were made. In intergroup comparisons, fructose significantly reduced the potencies of levorphanol and phenazocine, but not methadone or meperidine. In hexose/polyol specificity studies, tagatose and fructose significantly reduced the potency ratio for morphine, whereas glucose, galactose, mannose and the polyols, sorbitol and xylitol, caused no significant decrease in potency. Fructose, tagatose, glucose and mannose (5 g/kg, i.p.) were tested for effects on brain morphine levels 30 min after morphine (60 min after sugar), and all four sugars significantly increased brain morphine relative to saline-pretreated controls. It is concluded that the antagonism of morphine by acute sugar administration shows specificity for certain sugars and occurs despite sugar-induced increases in the distribution of morphine to the brain. Furthermore, the effects of fructose show an opiate specificity similar to that of glucose on antinociception observed previously in our laboratory, except that methadone was also significantly inhibited in the present study, when a repeated-testing experimental design was used.

Animals↗

An insulin-independent mechanism of intrathecal morphine-induced hypoglycemia in mice: mediation through a central alpha-2 adrenergic pathway.

Studies on the mechanism of the hypoglycemia caused by the i.t. administration of morphine (40 micrograms) to nonfasted, unanesthetized mice included assessment of effects of i.t. morphine on circulating levels of immunoreactive insulin and glucagon, on body temperature, as well as testing the effects of i.p. pretreatment with antagonists of cholinergic, beta adrenergic, alpha-1 adrenergic, alpha-2 adrenergic, serotonergic and opioid receptors. Serum levels of insulin were not significantly affected at 30 and 60 min after i.t. morphine, but plasma glucagon levels were significantly increased at both time points. Rectal temperature decreased significantly in mice given either saline or morphine i.t., but there was no significant difference between the two groups over time. Atropine (2 mg/kg), propranolol (10 mg/kg), prazosin (2 mg/kg) and methysergide (2 mg/kg) did not affect morphine-induced hypoglycemia. Naloxone (20 mg/kg) antagonized i.t. morphine. Mecamylamine (2 mg/kg) produced a moderate hypoglycemia in control mice, which appeared to be additive to that caused by i.t. morphine. Yohimbine (1-4 mg/kg i.p.) also produced a moderate hypoglycemia in control mice, but caused a dose-related antagonism of i.t. morphine. The centrally active alpha-2 antagonist, L-657,743 (2S-trans)-1,3,4,5',6,6',7,12b-octahydro-1',3'-dimethylspiro -(2H-benzofuro- (2,3-a)quinolizine-2,4'(1'H)pyrimidin)-2-(3'H)-one hydrochloride) (4-20 mg/kg i.p.), but not the peripherally selective alpha-2 antagonist, L-659,066 (2R-trans)-N-(2-(1,3,4,6,7,12b-he xahydro-2'- oxospiro(2H-benzofuro(2,3-a) quinolizine-2,4-imidazolidin)-3'-yl)ethyl)methanesulfonamide hydrochloride) (4-20 mg/kg i.p.), caused a dose-related antagonism of i.t. morphine. The i.t. coadministration of yohimbine (2 or 10 micrograms) or L-659,066 (10 micrograms) with morphine exhibited no antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Nursing interventions for families of cardiac surgery patients.

Caring for the cardiac surgery patient includes intervening with the patient's family members. It is important for the nurse to acquire the knowledge base to implement appropriate interventions with family members. An intervention program was designed to meet the needs of family members of cardiac surgery patients based on a compilation of previous research data. This program included providing educational classes for the nursing staff as well as giving written information and support to the family member while visiting in the intensive care unit. A visiting intervention checklist was given to each nurse to initiate for each family member at all visits. Family members who received the intervention program reported higher satisfaction of needs and lower anxiety levels than those family members who did not receive the program.

Cardiac Surgical Procedures↗

Cardiac transplantation.

Cardiac transplantation has emerged as an acceptable treatment for patients with end-stage cardiac disease. As a result, it is important for the critical care nurse to understand the principles associated with this procedure and to anticipate complications for this population. This article has reviewed the historical evolution of cardiac transplantation, identified recipient and donor selection criteria, and described the operative technique. Principles of immunosuppression are addressed as compulsory knowledge for the nurse caring for these patients and common immunosuppression agents are delineated. Complications of the early postoperative period are those most commonly encountered by the critical care nurse and include acute cardiac failure, hemorrhage, ECG abnormalities, rejection, infection, and acute renal failure. Frequently occurring nursing diagnoses are listed for cardiac transplant patients during the critical care phase and a care plan is demonstrated. Recognition and treatment of complications in the intensive care unit and the development of a plan of care for the patient by the critical care nurse are crucial to the success of cardiac transplantation.

Acute Kidney Injury↗

Induction and characterization of acrosome reaction in equine spermatozoa.

Equine spermatozoa were incubated in a chemically defined medium for 8 hours. The medium preserved spermatozoal viability, as assessed by total spermatozoal motility, progressive spermatozoal motility, and spermatozoal exclusion of eosin stain. Effects of time and divalent cation ionophore, A23187, on the occurrence and character of the spermatozoal acrosome reaction were determined. Two light microscopic assays, a triple-stain technique and a chlortetracycline fluorescence assay, were calibrated with transmission electron microscopy for detection of the acrosome reaction. Incubation time and A23187 addition increased the percentage of acrosome reactions in sperm populations (P less than 0.05).

Acrosome↗

Relationship of high intensity step-up lighting to bone ash and growth plate closure of the tarso-metatarsus in turkeys.

The reduced lameness observed in turkeys reared in a high intensity step-up (HISU) lighting programme as compared to a low intensity step-down (LISD) lighting regimen cannot be explained by differences in the inorganic matrix of the bone, because the proportions of bone ash, bone ash calcium, and bone ash phosphorus did not differ between lighting programmes. At 17 weeks of age, there was a significant difference in the proportion of closed growth plates in males reared on the HISU programme rather than on LISD lighting. These results support the hypothesis that HISU lighting reduces lameness by promoting earlier growth plate closure of long bones.

Animals↗

The meaning of role strain.

Explicating the meaning of the concept of role strain is important in role theory formulation, an area requiring further development to provide explanations and predictions for both patient and provider roles. In this analysis, the use of the term role strain is traced from the structural-functionalist and symbolic-interactionist perspectives. Descriptive, stipulative, and connotative definitions of role strain are derived, and necessary and relevant properties are proposed. Antecedent and intervening conditions for role strain are outlined from the literature. Role strain manifestations and empirical referents are presented, and an initial step is taken toward a theoretical formulation by defining role strain within the context of role stress.

Anxiety↗

Determination of the time course of capacitation in mouse spermatozoa using a chlortetracycline fluorescence assay.

The heads of mouse spermatozoa obtained 5 min after release from the excised caudae epididymides showed a characteristic fluorescence pattern in the presence of the fluorophore chlortetracycline (CTC). There was uniform fluorescence over the entire head with about half the sperm population showing a brighter line of fluorescence across the equatorial segment; this fluorescence pattern was designated "F". After 90-min incubation in culture medium (CM) containing 2% (w/v) bovine serum albumin, most of the sperm heads showed a dark band of nonfluorescence over the equatorial and postequatorial segment, while the anterior portion of the head showed bright fluorescence. This fluorescence pattern was designated "B." The time course for the disappearance of pattern F matched the time course of the appearance of pattern B, with a half-time of 30 min. The transformation was complete in 90 min. At longer times of incubation in CM, the percentage of spermatozoa showing pattern B declined; fluorescence over the entire head was lost, characteristic of the pattern for acrosome-reacted sperm (P. M. Saling and B. T. Storey (1979). J. Cell Biol. 83, 544-555). Mouse sperm showing pattern B were able to undergo the acrosome reaction, either spontaneously or by induction with acid-solubilized zonae pellucidae from mouse eggs (H.M. Florman and B. T. Storey (1982). Dev. Biol. 91, 121-130). The latter reaction was blocked by its specific inhibitor 3-quinuclidinyl benzilate (QNB). Mouse sperm showing pattern F could not be induced to undergo the acrosome reaction by exposure to solubilized zonae. This implies that the change from fluorescence pattern F to fluorescence pattern B corresponds with changes in the sperm which make them susceptible to undergo the acrosome reaction. This change occurs during the time interval previously determined to be needed for capacitation of mouse sperm in vitro in CM (M. Inoue and D. P. Wolf (1975). Biol. Reprod. 13, 340-346). These results imply that spermatozoa showing CTC fluorescence pattern B can be considered to be capacitated and that a functional definition for capacitation is the acquired ability to undergo the acrosome reaction rapidly when treated with acid-solubilized zonae pellucidae. The CTC fluorescence assay provides for the first time a means to monitor the time course of epididymal mouse sperm capacitation in vitro.

Acrosome↗

Binding of mouse spermatozoa to the zonae pellucidae of mouse eggs in cumulus: evidence that the acrosomes remain substantially intact.

Cumulus-intact mouse eggs inseminated in vitro with capacitated mouse sperm have sperm bound to the zonae pellucidae as early as 20 min postinsemination. Maximal sperm binding was observed at 60 min, after which time the number of sperm bound per egg decreased to about 30% of maximal. This extent of binding remained constant from 120 to 180 min postinsemination. All the sperm bound to the zonae had intact acrosomes as determined by chlortetracycline fluorescence assay. The sperm binding was retarded during the first 60 min by 3-quinuclidinyl benzilate, a specific inhibitor of the acrosome reaction induced by zona glycoprotein, but this compound had no effect on sperm binding during the next 60 min. The observation that sperm, which bind to zonae pellucidae after traversing the cumulus, have intact acrosomes is consistent with the same observation of intact acrosomes made with sperm binding to cumulus-free eggs [Saling and Storey (1979). J. Cell Biol. 83:544-555], and further supports the hypothesis that the sequence of events leading to fertilization of mouse eggs is: binding of intact sperm to the zona pellucida followed by the acrosome reaction induced by zona glycoprotein.

Acrosome↗

Diabetes mellitus, hyperadrenocorticism, and hypothyroidism in a dog.

An unusual combination of three endocrinopathies found in one dog is described. A six-year-old, spayed female, mixed-breed dog presented with polyuria, polydipsia, polyphagia, and weight loss. She was diagnosed with diabetes mellitus but was suspected of having insulin resistance and was diagnosed subsequently with hyperadrenocorticism. Persistent hypercholesterolemia led to the suspicion and eventual diagnosis of hypothyroidism. The dog has responded well to medical therapy, and her clinical signs and biochemical changes have resolved. A literature search did not identify a similar-reported polyendocrinopathy.

Adrenocortical Hyperfunction↗