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Biomedical subjects

R Clark

Publications and source records attributed to R Clark.

At least 271 records · Page 15Linked to original sources
PubMed1990

Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product.

Krev-1 is known to suppress transformation by ras. However, the mechanism of the suppression is unclear. The protein product of Krev-1, Rap1A-p21, is identical to Ras-p21 proteins in the region where interaction with guanosine triphosphatase (GTPase) activating protein (GAP) is believed to occur. Therefore, the ability of GAP to interact with Rap1A-p21 was tested. Rap1A-p21 was not activated by GAP but bound tightly to GAP and was an effective competitive inhibitor of GAP-mediated Ras-GTPase activity. Binding of GAP to Rap1A-p21 was strictly guanosine triphosphate (GTP)-dependent. The ability of Rap1A-p21 to bind tightly to GAP may account for Krev-1 suppression of transformation by ras. This may occur by preventing interaction of GAP with Ras-p21 or with other cellular proteins necessary for GAP-mediated Ras GTPase activity.

Binding, Competitive↗
PubMed1990

Effects of a novel PAF antagonist, E6123, on PAF-induced biological responses.

E6123 is a new member of the benzodiazepine class of PAF antagonists. Although it has similar activity in vitro to the two representative antagonists WEB2347 and Y24180, in vivo it is far more active than these compounds. Thus E6123 was effective in inhibiting dose-dependently PAF-induced bronchoconstriction when administered orally or intravenously (IC50 1.0 and 1.3 micrograms/Kg, respectively, at 3 hr), and had a minimum effective dose of 10 micrograms/Kg and 3 micrograms/Kg, respectively, against PAF-induced hematoconcentration and edema at 3 hr after oral administration. Furthermore, E6123 protects mice from PAF-induced death dose-dependently (ED50 7 micrograms/Kg at 3 hr). In conclusion, E6123 should prove valuable in pharmacological and clinical research into the roles of PAF, and in therapy of diseases such as asthma, in which PAF is assumed to play a pathological role.

Animals↗
PubMed1990

Discriminative stimulus properties of phenytoin in the pigeon: determination via a cumulative dosing procedure.

Pigeons were trained in a cumulative dosing procedure to emit one response in the presence of 15 mg/kg phenytoin and another response in the absence of phenytoin. After reliable discrimination was established, generalization tests with other anticonvulsant drugs were conducted. Ethosuximide (20-120 mg/kg) and methsuximide (25-100 mg/kg) engendered very little phenytoin-appropriate responding. Clonazepam (0.125-1 mg/kg) engendered more phenytoin-appropriate responding, but less than the training dose of phenytoin. Similar results were obtained when these drugs were administered in conventional single dose per session generalization tests. When tested in that fashion, mephenytoin (80 and 160 mg/kg) engendered some phenytoin-appropriate responding, but less than the training dose of phenytoin. Administering 10 mg/kg pentylenetetrazol in combination with 5, 10, 15, and 20 mg/kg cumulative doses of phenytoin reduced phenytoin-appropriate responding relative to levels obtained with these doses of phenytoin alone.

Animals↗
PubMed1990

Cutaneous zygomycosis in a diabetic HTLV-I-seropositive man.

Zygomycosis, an invasive fungal infection, is usually seen in persons with diabetes, particularly in those with diabetic ketoacidosis. The infection most frequently occurs in the rhinocerebral region and rapidly spreads, causing a swift demise. Rarely, the infection is confined to the cutaneous tissues. We describe a 31-year-old man seropositive for human T lymphotropic virus type I who had diabetic ketoacidosis with zygomycosis confined to the right arm. The lesion was presumed initially to be a bacterial infection but did not respond to conventional antimicrobial therapy. The arm lesion was cultured, and Rhizopus arrhizus was isolated. The patient responded well to a combination of amphotericin B and extensive surgical debridements. Our case emphasizes the importance of maintaining a high index of suspicion of cutaneous zygomycotic infections in the impaired host, especially of those in patients with diabetes, who do not respond to initial antimicrobial treatment.

Adult↗
PubMed1990

Measuring the activities of daily living: comparisons across national surveys.

The "activities of daily living," or ADLs, are the basic tasks of everyday life, such as eating, bathing, dressing, toileting, and transferring. Reported estimates of the size of the elderly population with ADL disabilities differ substantially across national surveys. Differences in which ADL items are being measured and in what constitutes a disability account for much of the variation. Other likely explanations are differences in sample design, sample size, survey methodology, and age structure of the population to which the sample refers. When essentially equivalent ADL measures are compared, estimates for the community-based population vary by up to 3.1 percentage points; and for the institutionalized population, with the exception of toileting, by no more than 3.2 percentage points. As small as these differences are in absolute terms, they can be large in percent differences across surveys. For example, the National Medical Expenditure Survey estimates that there are 60 percent more elderly people with ADL problems than does the Supplement on Aging.

Activities of Daily Living↗
PubMed1990

Supportive housing for the chronically mentally ill. Matching clients with community environments.

The need for permanent housing for the chronically mentally ill has received a great deal of attention over the last several years. One response to the problem has been the development of supportive housing, that is, non-facility-based permanent homes with placement based on clients' functional capabilities and preferences. However, little research has focused on assessing the match between clients and environmental requirements. This study begins to identify the social and clinical characteristics of clients that contribute to selection into different types of housing environments. Ninety-one clients were sampled from the supportive housing services of a major provider in two New England states. Logistic regression was used to estimate the probability that clients will be placed into apartments vs. other, more restricted settings, based on their clinical and social characteristics. Findings show that the primary determinants of placement were clinical severity, early family history, and adequacy of family support. The less severely ill and better functioning the client, the more likely that he or she was placed in an apartment. This was mitigated, however, by the availability and adequacy of family support. In addition, clients with early family disruptions were also less likely to be placed in apartments. Findings are discussed in light of their implications for providing permanent housing placements for chronically mentally ill persons and for factors in future research to evaluate the success of placement.

Adult↗
PubMed1990

Candida albicans infected pseudocyst in a postpartum woman.

We have presented the case of a postpartum woman with a pseudocyst infected with C albicans and have reviewed the relevant literature. The patient did well with surgical drainage of the pseudocyst and adjunctive therapy with amphotericin B. Candida species isolated from a pancreatic pseudocyst or abscess should be considered pathogens, and the patient should receive aggressive therapy.

Acute Disease↗
PubMed1990

Complications of extracorporeal membrane oxygenation in neonates.

In cases of severe respiratory failure, cardiopulmonary bypass has been used as support until cardiac and pulmonary recovery occurs. We report the Wilford Hall USAF Medical Center experience with extracorporeal membrane oxygenation (ECMO) and its associated complications. From July 1985 to March 1989, 57 neonates were placed on membrane oxygenators. The overall survival was 79%. Technical complications encountered included catheter-related problems, mechanical complications of the pump apparatus, and hemorrhage. Hemorrhagic complications were the most frequent and devastating complications encountered. Intracranial hemorrhage accounted for six deaths associated with bypass. Extracorporeal membrane oxygenation is successful in significantly improving survival of neonates whose predicted mortality approaches 100% with conventional treatment. The rate of infant mortality using the membrane oxygenator is not affected by technical complications related to catheter position, mechanical problems with the circuit, or hemorrhage, excluding intracranial hemorrhage. The major cause of death of infants receiving extracorporeal membrane oxygenation is the underlying disease process leading to cardiopulmonary failure.

Catheterization, Central Venous↗
PubMed1990

Monophasic versus biphasic cardiac stimulation: mechanism of decreased energy requirements.

The purpose of the present study was to examine the effects of monophasic and biphasic stimulation under conditions of full and incomplete repolarization in an in vivo dog model and in an in vitro rabbit ventricular single cell model. Strength-interval curves were constructed with monophasic cathodal stimulation and biphasic subthreshold anodal followed by cathodal stimulation in dogs prior to and late after left anterior descending coronary artery occlusion. At the monophasic absolute refractory period plus 10 msec, less cathodal current was required for biphasic compared to monophasic stimulation (P = 0.04). Moreover, the biphasic absolute ventricular refractory period (116 +/- 8 msec) was significantly shorter than the monophasic absolute ventricular refractory period (136 +/- 15 msec) (P less than 0.02). At coupling intervals greater than 30 msec after the monophasic absolute ventricular refractory period, there was no distinction between monophasic and biphasic stimuli. Similarly enhanced excitability was observed with biphasic stimuli in infarcted hearts. Voltage clamp measurements mimicking conditions of the in vivo studies demonstrated that when repolarization is incomplete, a hyperpolarizing prepulse reactivates additional sodium current resulting in enhanced excitability. In conclusion, biphasic stimulation consisting of a hyperpolarizing anodal prepulse followed by a cathodal pulse decreases the current required for excitation compared to cathodal monophasic stimulation in a critical zone near the ventricular absolute refractory period.

Animals↗
PubMed1990

Molecular cloning and expression of a G25K cDNA, the human homolog of the yeast cell cycle gene CDC42.

G25K is a low-molecular-mass GTP-binding protein with a broad distribution in mammalian tissues. A cDNA clone was isolated by using oligonucleotides corresponding to the partial amino acid sequence of purified human G25K. The cDNA encodes an 191-amino-acid polypeptide containing GTP-binding consensus sequences and a putative farnesylation site at the C terminus. The sequence exhibits 50 and 70% identities to the mammalian rho and rac proteins, respectively, and an 80% identity to the Saccharomyces cerevisiae CDC42 gene product. Insect Sf9 cells infected with recombinant baculovirus vectors expressing the G25K cDNA produced a 25-kDa protein that bound GTP and was recognized by antibodies specifically reactive to G25K. G25K appears to be the human homolog of the CDC42 gene product, since expression of the G25K cDNA in S. cerevisiae suppressed both cdc42-1 and cdc24-4 temperature-sensitive lethal mutations.

Amino Acid Sequence↗
PubMed1990

Biochemical characterization of baculovirus-expressed rap1A/Krev-1 and its regulation by GTPase-activating proteins.

Normal human rap1A and 35A rap1A (which encodes a protein with a Thr-35----Ala mutation) were cloned into a baculovirus transfer vector and expressed in Sf9 insect cells. The resulting proteins were purified, and their nucleotide binding, GTPase activities, and responsiveness to GTPase-activating proteins (GAPs) were characterized and compared with those of Rap1 purified from human neutrophils. Recombinant wild-type Rap1A bound GTP gamma S, GTP, and GDP with affinities similar to those observed for neutrophil Rap1 protein. The rate of exchange of GTP by Rap1 without Mg2+ was much slower than that by Ras. The basal GTPase activities by both recombinant proteins were lower than that observed with the neutrophil Rap1, but the GTPase activity of the neutrophil and wild-type recombinant Rap1 proteins could be stimulated to similar levels by Rap-GAP activity in neutrophil cytosol. In contrast to wild-type Rap1A, the GTPase activity of 35A Rap was unresponsive to Rap-GAP stimulation. Neither recombinant Rap1A nor neutrophil Rap1 protein GTPase activity could be stimulated by recombinant Ras-GAP at a concentration 25-fold higher than that required to hydrolyze 50% of H-Ras-bound GTP under similar conditions. These results suggest that the putative effector domains (amino acids 32 to 40) shared between Rap1 and Ras are functionally similar and interact with their respective GAPs. However, although Rap1 and Ras are identical in this region, secondary structure or additional regions must confer the ability to respond to GAPs.

Animals↗
PubMed1990

Economic dependency and divorce: implications for the private sphere.

"This paper asserts a connection between economic dependency and divorce. It argues that, because dependency deprives women of equal access to the public sphere and because it confines them, through normative definition, to the private sphere, it reduces their likelihood of seeking divorce. The paper also argues, contrary to recent findings, that socioeconomic development should be linearly and positively associated with divorce. Data from 51 nations are examined and multiple regression analysis [suggests] considerable support for these arguments."

Demography↗
PubMed1990

Pharmacological activities of a novel thienodiazepine derivative as a platelet-activating factor antagonist.

(S)-(+)-6-(2-Chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl - 2,3,4,5 - tetrahydro - 8H - pyrido[4',3':4,5] thieno[3,2-fl-[1,2,4]triazolo]4,3-a][1,4]diazepine (E-6123) is a newly synthesized platelet-activating factor (PAF) antagonist. The effects of E-6123 on in vitro and in vivo PAF-induced responses were investigated. The IC50 values of E-6123 on 3H-PAF binding to human and guinea pig platelets were 2.7 and 3.0 nmol/l, respectively, and those on PAF-induced platelet aggregation in platelet-rich plasma of human, guinea pig and beagle dog were 10.1, 14.7 and 16 nmol/l, respectively. Oral administration of E-6123 at 3 and 10 micrograms/kg to dogs inhibited ex vivo PAF-induced platelet aggregation in a dose-dependent manner. In guinea pigs, E-6123 at 3 micrograms/kg completely inhibited ex vivo PAF-induced platelet aggregation up to 8 h and the inhibition was still significant at 24 h after administration. Occupancy of the platelet PAF receptor by E-6123 at 3 h and 24 h after administration amounted to 80% and 56%, respectively. Bronchoconstriction induced by PAF injection in guinea pigs was inhibited dose-dependently by oral or intravenous administration of E-6123 at similar doses. The IC50 value of E-6123 at 3 h after oral administration was 1 microgram/kg. Oral administration of E-6123 at 3 micrograms/kg inhibited the bronchoconstriction by more than 90% up to 8 h. Hemato-concentration induced by PAF injection in guinea pigs was inhibited by oral administration of E-6123 at 10 micrograms/kg. E-6123 also protected mice from PAF injection-induced death in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Extracorporeal membrane oxygenation in the newborn.

Extracorporeal membrane oxygenation (ECMO) is used in the treatment of reversible pulmonary disease in the newborn. The ECMO program at Wilford Hall USAF Medical Center began in 1985 and to date, 57 patients have been placed on bypass for a mean of 125 hours. The indications for ECMO are severe, prolonged hypoxemia in patients with an estimated mortality of greater than 90% using conventional ventilator support. The major diagnoses in the patients placed on ECMO were meconium aspiration, congenital diaphragmatic hernia, and neonatal sepsis or pneumonia. Overall survival was 79%, or 45 out of 57. The most frequent complications were intracranial hemorrhage as well as hemorrhage from the surgical site. We have found ECMO to be an extremely valuable adjunct in the care of the critically ill newborn and believe it can significantly improve survival in infants with reversible pulmonary disease.

Extracorporeal Membrane Oxygenation↗
PubMed1990

Open lung biopsy in the critically ill newborn.

Experience with 17 open lung biopsies in critically ill premature neonates was reviewed. Despite their small size, prematurity, and near maximal ventilator requirements, the infants suffered no significant complications. In three cases, an infectious agent was identified. In one case end-stage lung fibrosis associated with persistent (greater than 3 months), severe respiratory failure prompted termination of support. In the remainder of the cases, definitively ruling out infection allowed the confident trial of a course of steroids in an attempt to treat bronchopulmonary dysplasia. Unlike older patients, the definitive diagnosis of no infection in the premature neonate is just as informative as the diagnosis of an infection. Used judiciously, open lung biopsy can be performed in the premature infant with acceptable morbidity and mortality.

Anti-Bacterial Agents↗
PubMed1990

Morphometric analysis of Psoroptes spp. mites from bighorn sheep, mule deer, cattle, and rabbits.

A morphometric study of Psoroptes spp. mites was conducted to address difficulties encountered in species identification and to provide insights into the phylogenetic relationships between mites found on different hosts. A discriminant analysis employing 9 morphologic characters revealed that the lengths of the outer opisthosomal setae and the lateral margins of the opisthosomal knobs were the 2 most important characters for grouping mites according to host species. This analysis clearly separated mites collected from allopatric populations of bighorn sheep, rabbits, and cattle into discrete groups. However, differences were not detected between mites collected from sympatric populations of infested mule deer and bighorn sheep, suggesting that these mites were not host specific and represented a single interbreeding population. Differences also were not detected among mites collected from the ears and body of bighorn sheep and rabbits, demonstrating that the location of mites on a given host should not be used as a primary criterion in species identification.

Animals↗
PubMed1989

Production of and responsiveness to transforming growth factor-beta in normal and oncogene-transformed human mammary epithelial cells.

Transforming growth factors-beta (TGF beta) are a family of closely related, ubiquitously expressed growth factors with the common properties of induction of growth inhibition and expression of differentiation-related markers in epithelial cells. We investigated the role of TGF beta 1 in growth regulation of normal human mammary epithelial cells and in benzo(a)pyrene immortalized sublines further transformed by oncogenes in retroviral vectors. The normal cells were markedly growth inhibited by TGF beta 1, produced TGF beta in a latent form, and expressed TGF beta receptors. In the immortalized cells, both TGF beta-induced growth inhibition and TGF beta receptor binding were reduced. With the single oncogenes v-Ha-ras, v-mos, and SV40 T, growth sensitivity to TGF beta 1 increased, but TGF beta production or TGF beta receptor expression was not altered. Transformation to full malignancy by both SV40 T and v-Ha-ras led to escape from growth inhibition by TGF beta under anchorage-independent, but not anchorage-dependent, conditions without affecting TGF beta production or receptor characteristics. Thus, modulation of TGF beta growth responsiveness in these normal and oncogene transformed human mammary epithelial cells apparently occurs at a level distal to TGF beta receptor binding and is not solely correlated to expression of transforming oncogenes. Further, modulation of TGF beta production is not an indicator of malignant transformation in this system.

Benzo(a)pyrene↗