Search PubMed⌕ Search

Biomedical subjects

R Clark

Publications and source records attributed to R Clark.

At least 37 records · Page 2Linked to original sources
PubMed1992

The role of mental morbidity in the nursing home experience.

The history of a newly admitted cohort to eight nursing homes (N = 454) was studied prospectively over the first year of residence. Data were gathered at admission, 2 months, and 1 year, and included full psychiatric examination and staff reports of behavior. Chart reviews collected additional data on preadmission and postdischarge information. At admission, 80% of the population had mental illnesses, 60% of which were dementia, and about half of demented patients had other complicating mental illnesses. Use of mixed-effects linear model analysis revealed significant associations of mental morbidity, restraints, and psychotropic medication with behaviors indicative of noncoping and nonadaptation to the nursing home settings.

Adaptation, Psychological↗
PubMed1992

Prolongation of graft survival in primate allograft transplantation by yttrium-90-labeled anti-Tac in conjunction with granulocyte colony-stimulating factor.

High-affinity IL-2 receptors are expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting T cells. To exploit this difference in IL-2R expression, anti-Tac, a murine monoclonal antibody specific for the IL-2R alpha subunit, was used to inhibit organ allograft rejection. To enhance its effector function, anti-Tac was armed by chelation with yttrium-90, a pure beta-emitting radionuclide. Animals received no immunosuppression (n = 5, group I, controls), unmodified anti-Tac (n = 5, 1 mg/kg q.o.d., group II), or 90Y-anti-Tac (n = 5, 1.6 mCi/kg divided into four doses, group III). The animals in group IV (n = 4) were treated identically to those in group III with the exception that 5 micrograms/kg/dose of granulocyte colony-stimulating factor was administered intramuscularly on the days when the yttrium-90 was given and on postoperative days 12 through 35 in order to reduce hematopoietic toxicity. Mean graft survival +/- S.E.M. for the control group was 8.2 +/- 0.5 days as compared with 13.8 +/- 2.1 days (P < 0.05) for those monkeys treated with unmodified anti-Tac. Graft survival was further prolonged in animals of group III that received 90Y-anti-Tac, with a mean graft survival of 45.0 +/- 11.8 days; however, three of the five monkeys retained viable grafts within this group but died secondary to bone marrow suppression. In comparison, the monkeys in group IV that were treated with G-CSF in conjunction with 90Y-anti-Tac had a mean graft survival of 49.2 +/- 2.9 days. In contrast to group III there were no deaths in the group (IV) receiving G-CSF. Furthermore, animals in group IV had a reduced magnitude and shortened duration of irradiation-induced neutropenia when compared with that observed in group III animals that did not receive G-CSF. Thus, treatment with 90Y-anti-Tac in conjunction with G-CSF may have potential applications in organ transplantation and the treatment of IL-2 receptor-expressing neoplastic diseases.

Animals↗
PubMed1992

Localization of the rap1GAP catalytic domain and sites of phosphorylation by mutational analysis.

rap1GAP is a GTPase-activating protein that specifically stimulates the GTP hydrolytic rate of p21rap1. We have defined the catalytic domain of rap1GAP by constructing a series of cDNAs coding for mutant proteins progressively deleted at the amino- and carboxy-terminal ends. Analysis of the purified mutant proteins shows that of 663 amino acid residues, only amino acids 75 to 416 are necessary for full GAP activity. Further truncation at the amino terminus resulted in complete loss of catalytic activity, whereas removal of additional carboxy-terminal residues dramatically accelerated the degradation of the protein in vivo. The catalytic domain we have defined excludes the region of rap1GAP which undergoes phosphorylation on serine residues. We have further defined this phosphoacceptor region of rap1GAP by introducing point mutations at specific serine residues and comparing the phosphopeptide maps of the mutant proteins. Two of the sites of phosphorylation by cyclic AMP (cAMP)-dependent kinase were localized to serine residues 490 and 499, and one site of phosphorylation by p34cdc2 was localized to serine 484. In vivo, rap1GAP undergoes phosphorylation at four distinct sites, two of which appear to be identical to the sites phosphorylated by cAMP-dependent kinase in vitro.

Amino Acid Sequence↗
PubMed1992

Mutational and kinetic analyses of the GTPase-activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity.

The GTPase-activating protein (GAP) stimulates the GTPase reaction of p21 by 5 orders of magnitude such that the kcat of the reaction is increased to 19 s-1. Mutations of residues in loop L1 (Gly-12 and Gly-13), in loop L2 (Thr-35 and Asp-38), and in loop L4 (Gln-61 and Glu-63) influence the reaction in different ways, but all of these mutant p21 proteins still form complexes with GAP. The C-terminal domain of the human GAP gene product, GAP334, which comprises residues 714 to 1047, is 20 times less active than full-length GAP on a molar basis and has a fourfold lower affinity. This finding indicates that the N terminus of GAP containing the SH2 domains modifies the interaction between the catalytic domain and p21.

Amino Acid Sequence↗
PubMed1992

Verapamil prevents insulin antinatriuresis in euglycemic rats.

To determine whether calcium entry is necessary for insulin antinatriuresis, urinary sodium excretion was determined before and during euglycemic insulin administration in rats receiving verapamil (10 micrograms.kg-1.min-1) or vehicle. In vehicle rats, insulin reduced sodium excretion from 2.7 +/- 0.5 to 0.98 +/- 0.2 mu eq/min (P less than 0.05) without altering arterial pressure or inulin clearance. Insulin did not reduce sodium excretion in rats receiving verapamil. Baseline mean arterial pressure was lower in verapamil rats than in vehicle rats. To exclude the possibility that lower baseline arterial pressures prevented insulin antinatriuresis, insulin's effect on sodium excretion was determined in rats receiving captopril at a dose that reduced arterial pressure to the level observed in verapamil rats, and in verapamil rats with angiotensin II levels fixed to maintain arterial pressure equivalent to vehicle rats. In captopril rats, insulin reduced (P less than 0.05) sodium excretion from 1.07 +/- 0.3 to 0.3 +/- 0.01 mu eq/min, even though arterial pressure was not different from that in verapamil rats. Insulin failed to reduce sodium excretion in verapamil rats receiving angiotensin II. Thus verapamil prevents insulin antinatriuresis by renal mechanisms related to inhibition of calcium entry. Additionally, insulin antinatriuresis is independent of angiotensin II.

Animals↗
PubMed1992

Embryonic stem cell-derived cystic embryoid bodies form vascular channels: an in vitro model of blood vessel development.

Murine embryonic stem cells can differentiate in vitro to form cystic embryoid bodies (CEB) that contain different structures and cell types. The blood islands are one such structure that consist of immature hematopoietic cells surrounded by endothelial cells, the first identifiable vascular cells. CEBs differentiated in vitro developed blood islands initially, and subsequently these blood islands matured to form vascular channels containing hematopoietic cells. Phase contrast microscopy demonstrated the presence of channels in mature CEBs grown in suspension culture, and high resolution light and electron microscopy showed that the cells lining these channels were endothelial cells. The channels appeared less organized than the vasculature of the mature yolk sac. The hematopoietic cells were occasionally seen 'flowing' through the CEB channels, although their numbers were reduced relative to the yolk sac. Analysis of primary CEB cultures showed the presence of cells with two characteristics of endothelial cells: approximately 30% of the cells labelled with fluorescent acetylated low density lipoprotein and a small number of cells were positive for von Willebrand's factor by immunostaining. Thus we conclude that a primitive vasculature forms in CEBs differentiated in vitro, and that not only primary differentiation of endothelial cells but also some aspects of vascular maturation are intrinsic to this cell culture system. CEBs are therefore a useful model for the study of developmental blood vessel formation.

Animals↗
PubMed1992

Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 16 non-Japanese cases.

Kabuki make-up (Niikawa-Kuroki) syndrome has been described mainly in Japanese patients. In this paper we report sixteen new cases from Europe and North America, suggesting that Kabuki make-up syndrome may be more common outside of Japan than supposed. Their features are compared with those of the Japanese patients and most of our findings are similar to those previously reported. The facial phenotype is specific and easily recognizable, regardless of ethnic origin. Postnatal growth retardation and mild mental retardation are confirmed to be cardinal manifestations of the syndrome. Skeletal anomalies were present in all cases but most of the radiological changes were non-specific. The specificity of metacarpophalangeal pattern profile is not confirmed. Conversely, dermatoglyphic analysis is helpful in the diagnosis of this condition. Two differences have emerged between the Japanese patients and those in this study. Firstly, two-thirds of the patients in this series had significant neurological dysfunction other than mental retardation. Secondly, joint hypermobility appears more common in non-Japanese patients. Confirmation of these findings requires further studies.

Abnormalities, Multiple↗
PubMed1991

Activation of BPV-1 replication in vitro by the transcription factor E2.

Soluble extracts from uninfected murine cells supplemented with purified viral E1 and E2 proteins support the replication of exogenously added papilloma virus DNA. The E2 transactivator stimulates the binding of the E1 replication protein to the minimal origin of replication and activates DNA replication. These results support the concept that transcription factors have a direct role in the initiation of DNA replication in eukaryotes by participating in the assembly of a complex at the origin of replication.

Aphidicolin↗
PubMed1991

Evidence for regulation of the human ABL tyrosine kinase by a cellular inhibitor.

Phosphotyrosine cannot be detected on normal human ABL protein-tyrosine kinases, but activated oncogenic forms of the human ABL protein are phosphorylated on tyrosine in vivo. Activation of ABL can occur by substitution of the ABL first exon with breakpoint cluster region (BCR) sequences or by deletion of the noncatalytic SH3 (src homology region 3) domain. An alternative mode for the activation of the ABL kinases is hyperexpression at greater than 500-fold over endogenous levels. This is not a consequence of transphosphorylation of the hyperexpressed ABL molecules. ABL proteins translated in vitro lack phosphotyrosine, but tyrosine kinase activity is uncovered after immunoprecipitation and removal of lysate components. The rates of dephosphorylation of ABL and BCR-ABL fusion protein by phosphotyrosine-specific phosphatases are approximately the same. These combined results indicate that inhibition of ABL activity is reversible and suggest that a cellular component interacts noncovalently with ABL to inhibit its autophosphorylation.

Animals↗
PubMed1991

Molecular cloning of a GTPase activating protein specific for the Krev-1 protein p21rap1.

The rap1/Krev-1 gene encodes a ras-related protein that suppresses transformation by ras oncogenes. We have purified an 88 kd GTPase activating protein (GAP), specific for the rap1/Krev-1 gene product, from bovine brain. Based on partial amino acid sequences obtained from this protein, a 3.3 kb cDNA was isolated from a human brain library. Expression of the cDNA in insect Sf9 cells resulted in high level production of an 85-95 kd rap1GAP that specifically stimulated the GTPase activity of p21rap1. The complete deduced amino acid sequence is not homologous to any known protein sequences, including GAPs specific for p21ras. Northern and Western blotting analysis indicate that rap1GAP is not ubiquitously expressed and appears most abundant in fetal tissues and certain tumor cell lines, particularly the Wilms' kidney tumor, SK-NEP-1, and the melanoma, SK-MEL-3, cell lines.

Amino Acid Sequence↗
PubMed1991

Mammography and age: are we targeting the wrong women? A community survey of women and physicians.

To determine mammography use among women with a broad range of ages, the authors surveyed women aged 30 to 74 years and physicians practicing primary care in two eastern North Carolina counties. Twenty-five percent of women in their 30s had ever had a mammogram, and 34% intended to have one in the coming year. From 45% to 52% of women in their 40s, 50s, and 60s had ever had a mammogram, and 55% to 57% intended to have one in the next year. Thirty-seven percent of women aged 70 to 74 years had ever had a mammogram, and 40% intended to have one in the following year. Nineteen percent of physicians reported screening nearly all women aged 30 to 39 years, and 14% screened few women aged 50 to 74 years. Younger women were more worried about breast cancer than older women and assessed their risk as higher, attitudes that were generally associated with higher mammography utilization. These community surveys suggest that mammography use may be excessive among younger women; older women continue to be underscreened.

Adult↗
PubMed1991

Depression and mortality in nursing homes.

To determine the prevalence rates of major depressive disorder and of depressive symptoms and their relationship to mortality in nursing homes, research psychiatrists examined 454 consecutive new admissions and followed them up longitudinally for 1 year. Major depressive disorder occurred in 12.6% and 18.1% had depressive symptoms; the majority of cases were unrecognized by nursing home physicians and were untreated. Major depressive disorder, but not depressive symptoms, was a risk factor for mortality over 1 year independent of selected physical health measures and increased the likelihood of death by 59%. Because depression is a prevalent and treatable condition associated with increased mortality, recognition and treatment in nursing homes is imperative.

Activities of Daily Living↗
PubMed1991

Dyadic disturbances in cocaine-abusing mothers and their infants.

A recently developed instrument for the quantification of mother-infant interaction, the Parent-Child Early Relationship Assessment (PCERA), was used to observe drug-abusing mothers and their infants. Compared to the standardization sample used in the development of the PCERA, these drug-abusing mothers (N = 5) showed a tendency toward rigidity and overcontrol in their parenting, a lack of enjoyment and pleasure in relating to their infants, and limited emotional involvement and responsivity in their interaction. An analysis of the dyadic behaviors showed an overall reduction in reciprocity, mutual enjoyment, and regulation of interaction between mother and infant.

Adult↗
PubMed1991

Redefinition of cutaneous lymphatic drainage with the use of lymphoscintigraphy for malignant melanoma.

Lymphoscintigraphy was performed on 82 patients with melanoma registered at the University Melanoma Clinic. From these data, precise lymphatic drainage basins could be drawn for the head, neck, shoulder, and trunk. These drawings differed significantly from the classic anatomic studies, providing a functional look at the cutaneous lymphatic drainage. This new method correlates much better with clinical experiences and demonstrates much larger areas of ambiguous drainage than previously reported. Data from the lymphoscintigrams also emphasize the individuality of cutaneous lymphatic flow. The implications of these data in planning elective node dissections for intermediate thickness melanomas are obvious, since it is estimated that up to 59% of the dissections for trunk and head and neck primary melanomas may be misdirected if based on classic anatomic studies. The data indicate that all patients with head, neck, and shoulder lesions should undergo lymphoscintigraphy to define possible drainage basins at risk for metastatic disease. Similarly, truncal lesions require scintigrams except when they are within four well-defined areas with an extremely low probability of ambiguous drainage. Lesions in these areas show very reliable and predictable drainage to a single nodal group.

Antimony↗
PubMed1991

Identity of BCA200 and c-erbB-2 indicated by reactivity of monoclonal antibodies with recombinant c-erbB-2.

BCA200 has been described as a 200,000 Mr monomeric cell surface glycoprotein associated with human breast cancer. Since the physical properties and cellular distribution of BCA200 resemble those of c-erbB-2, antibodies to BCA200 were tested for the ability to bind a recombinant protein containing the c-erbB-2 extracellular domain (erbB-2 ECD). Three antibodies to distinct epitopes of BCA200 reacted with erbB-2 ECD but not with a control protein expressed in a similar baculovirus lysate. Control myeloma proteins and antibodies to four other antigens did not react with erbB-2 ECD. A protein with the expected molecular weight for erbB-2 ECD was also immunoprecipitated by anti-BCA200 antibody 520C9. We conclude that BCA200 is another synonym for c-erbB-2.

Antibodies, Monoclonal↗
PubMed1991

China White epidemic: an eastern United States emergency department experience.

STUDY OBJECTIVE: The purpose of this study was to isolate significant clinical or demographic findings concerning overdose patients treated during a China White (3-methyl fentanyl) epidemic and compare them with data for all unintentional narcotic overdose patients during a 24-month period. DESIGN: We reviewed charts from 85,246 patient visits to our emergency department during the 24-month period of January 1987 through December 1988 to study this narcotic epidemic. Data from the Allegheny County Coroner's Office pertaining to unintentional drug overdose deaths that occurred during this same period also were reviewed. SETTING: The first outbreak of narcotic overdoses in the eastern United States involving China White occurred in Allegheny County, Pennsylvania, in 1988. TYPE OF PARTICIPANTS: Patients were included if they met the criteria of a suspected unintentional narcotic overdose, but excluded if they were not given naloxone. INTERVENTIONS: Emergency physicians became suspicious of China White use after an unusual increase in narcotic overdoses presenting to the ED coupled with "routine drug of abuse" screens negative for opiates despite dramatic patient responses to naloxone. In most of the cases in which specific testing was done, there were positive indicators of fentanyl derivatives. Investigations found China White present in street drugs and paraphernalia. MEASUREMENTS AND MAIN RESULTS: A cluster was defined as a time period with a statistically significant increase in overdoses over the expected number for an interval of equal length. Although there were no significant clinical differences in case presentation during the 24-month period, there was a statistically significant 13-fold increase in overdoses during the September through November 1988 cluster (mean, 13 vs 0.95 per month, P less than .001 by Wilcoxon rank-sum test). A dramatic increase in unintentional drug overdose deaths occurred in the county during this cluster. A total of 18 fentanyl-positive unintentional drug overdose deaths, predominantly male (89%) and black (56%), with an age range of 19 to 44 years (mean, 34.9 years), were reported by the county coroner (13 during the cluster). Narcotic overdoses and unintentional drug overdose deaths declined sharply with confiscation of a clandestine China White laboratory. CONCLUSIONS: China White was responsible for a dramatic rise in unintentional drug overdose deaths in Allegheny County in 1988. There were no significant clinical differences between China White overdose survivors and other unintentional narcotic overdose victims. Overdoses responsive to naloxone with inconsistent routine toxicologic screens may be due to a fentanyl analogue.

Adult↗
PubMed1991

Case report: Chlamydia pneumoniae pneumonia in an HIV-infected man.

We report a case of an HIV-infected adult with Chlamydia pneumoniae. Our patient presented with a clinical picture suggestive of Pneumocystis carinii pneumonia (PCP), but did not respond to empiric anti-PCP therapy. The diagnosis was eventually confirmed by bronchoscopy and serology. C. pneumoniae pneumonia should be considered in the differential of pathogens that cause interstitial infiltrates in HIV-infected persons.

Chlamydia Infections↗