The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism.
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Biomedical subjects
Publications and source records attributed to K Clark.
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The Arabidopsis ETR1 gene codes for an ethylene hormone receptor that has striking sequence similarity with bacterial two-component regulators. This finding predicts that the ETR1 receptor transduces the ethylene signal through the phosphotransfer mechanisms established for a number of the bacterial regulators. To test this hypothesis, we have performed in vitro assays for ETR1 autokinase activity as well as for transfer of phosphate to the ETR1 receiver. So far, we have not detected either of these activities. Another question we are focusing on is the identity of protein substrates of the ETR1 receptor. Using the yeast two-hybrid system, we have obtained several clones to be subsequently characterized as potential interactors with ETR1.
BACKGROUND: Most cardiac catheterizations are performed via femoral artery access. Reported rates of both peripheral vascular complications and success rates for the use of manual and mechanical compression techniques to achieve femoral artery hemostasis after cardiac catheterization vary. OBJECTIVE: To determine is use of a mechanical clamp is as effective as standard manual pressure for femoral artery hemostasis after cardiac catheterization. METHODS: Subjects consisted of 720 patients from 2 community hospitals who had elective diagnostic cardiac catheterization via the femoral artery. The control group (n=343) received manual compression for hemostasis; the study group (n=377) received mechanical compression. Standard protocols were used for the 2 compression techniques. Pressure was applied for a minimum of 10 minutes for 5F and 6F sheaths and catheters and for a minimum of 15 minutes for 7F and 8F sheaths and catheters. Prospective data were collected and analyzed for each patients, including sheath or catheter size, blood pressure, height, weight, age, time from administration of local anesthetic to successful cannulation of the femoral artery, anticoagulation status, total compression time, physician performing the catheterization procedure, nurse or technician who obtained hemostasis, and complications. In follow-up, patients were asked site-specific and functional status questions 1 to 2 days after the catheterization procedure and again 3 days after the catheterization procedure. RESULTS: Data were analyzed by using frequency distributions, measures of central tendency, and measures of variability. Only 1 difference between the 2 groups was significant: manual compression time was 14.93 +/- minutes, whereas mechanical compression time was 17.13 +/- minutes. CONCLUSION: Mechanical compression is as effective as manual compression for femoral artery hemostasis after cardiac catheterization.
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A number of studies have shown conflicting results on the effect of epidural (EPI) analgesia on the length of labor. Combined spinal-epidural (CSE) and intrathecal analgesia (ITA) techniques have been used to provide pain relief for parturients, but currently there are few studies comparing EPI, CSE, and ITA techniques and their effect on the length of labor. Intrathecal opioids provide immediate pain relief for the parturient without autonomic, sensory, or motor blockade. The purpose of this retrospective study is to identify the effects of ITA on the length of labor compared with other regional anesthesia techniques. A total of 213 uncomplicated obstetric charts were reviewed in a 70-bed Air Force hospital that provided EPI, CSE, and ITA for obstetrical patients. The study consisted of the following four groups: (1) CSE (n = 76), (2) EPI(n = 41), (3) ITA (n = 49), and (4) no regional analgesia (NR) (n = 47). The results showed that the length of first-stage labor was statistically significantly less for those who received ITA compared with those who received CSE, EPI, and NR (P < .001). Second-stage labor was statistically significantly shorter for the NR group compared with the CSE and EPI groups (P < .01). No statistically significant difference was found between the length of second stage for ITA and NR groups. ITA analgesia shortened the first stage significantly in both primipara and multipara patients (P < .01). These results imply that the use of intrathecal opioids in the obstetrical patient does not prolong labor and seems to shorten the first stage of labor in both the primipara and multipara patients.
The migration, adhesion, and subsequent extravasation of leukocytes into inflamed tissues contribute to the pathogenesis of a variety of inflammatory diseases including asthma, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. The integrin adhesion receptor alpha 4 beta 1 expressed on leukocytes binds to the extracellular matrix protein fibronectin and to the cytokine inducible vascular cell adhesion molecule-1 (VCAM-1) at inflamed sites. Binding of alpha 4 beta 1 to VCAM-1 initiates firm adhesion of the leukocyte to the vascular endothelium followed by extravasation into the tissue. Monoclonal antibodies generated against either alpha 4 beta 1 or VCAM-1 can moderate this inflammatory response in a variety of animal models. Recently peptides containing a consensus LDV sequence based on the connecting segment-1 (CS-1) of fibronectin and cyclic peptides containing an RCD motif have shown promise in modulating leukocyte migration and inflammation presumably by blocking the interaction of alpha 4 beta 1 with VCAM-1. Here we describe novel, highly potent, cyclic peptides that competitively inhibit alpha 4 beta 1 binding to VCAM-1 and fibronectin at sub nanomolar concentrations. The structure of a representative analog was determined via NMR spectroscopy and used to facilitate optimization of peptide leads. The peptides discussed here utilize similar functional groups as the binding epitope of VCAM-1, inhibit lymphocyte migration in vivo, and are highly selective for alpha 4 beta 1. Furthermore the structure--activity relationships described here have provided a template for the structure-based design of small molecule antagonists of alpha 4 beta 1-mediated cell adhesion processes.
Tumor necrosis factor-alpha, interleukin-1, and endotoxin stimulate the expression of vascular endothelial cell (EC) adhesion molecules. Here we describe a novel pathway of adhesion molecule induction that is independent of exogenous factors, but which is dependent on integrin signaling and cell-cell interactions. Cells plated onto gelatin, fibronectin, collagen or fibrinogen, or anti-integrin antibodies, expressed increased amounts of E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. In contrast, ECs failed to express E-selectin when plated on poly-L-lysine or when plated on fibrinogen in the presence of attachment-inhibiting, cyclic Arg-Gly-Asp peptides. The duration and magnitude of adhesion molecule expression was dependent on EC density. Induction of E-selectin on ECs plated at confluent density was transient and returned to basal levels by 15 h after plating when only 7 +/- 2% (n = 5) of cells were positive. In contrast, cells plated at low density displayed a 17-fold greater expression of E-selectin than did high density ECs with 57 +/- 4% (n = 5) positive for E-selectin expression 15 h after plating, and significant expression still evident 72 h after plating. The confluency-dependent inhibition of expression of E-selectin was at least partly mediated through the cell junctional protein, platelet/endothelial cell adhesion molecule-1 (PECAM-1). Antibodies against PECAM-1, but not against VE-cadherin, increased E-selectin expression on confluent ECs. Co- culture of subconfluent ECs with PECAM-1- coated beads or with L cells transfected with full-length PECAM-1 or with a cytoplasmic truncation PECAM-1 mutant, inhibited E-selectin expression. In contrast, untransfected L cells or L cells transfected with an adhesion-defective domain 2 deletion PECAM-1 mutant failed to regulate E-selectin expression. In an in vitro model of wounding the wound front displayed an increase in the number of E-selectin-expressing cells, and also an increase in the intensity of expression of E-selectin positive cells compared to the nonwounded monolayer. Thus we propose that the EC junction, and in particular, the junctional molecule PECAM-1, is a powerful regulator of endothelial adhesiveness.
It is known that social drift to cities increases the urban prevalence for severe mental illnesses. Recent studies in England and Sweden have reported that being born in, or raised in, an urban area is also a risk factor for later developing schizophrenia. The present study utilized 1880 census data, the most complete enumeration of severely mentally ill individuals ever done in the United States, to examine the association of urban residence and severe mental illnesses. Individuals identified as having one of seven forms of 'insanity' (n = 91959) were allocated to their county of origin (n = 2661) in the census. Rates of 'insane' persons per 1000 population were calculated for each county. The counties were then divided by degree of urbanization based on the largest cities and the percentage of population living in towns of 4000 or more. The point prevalence of 'insanity' in the United States as a whole in 1880 was 1.8 per 1000. There was a significant association between 'insanity' by county and degree of urbanization, with odds ratios of 1.66 for urban, 1.46 for semi-urban, and 1.44 for semi-rural, and 1.37 for rural, using completely rural counties as a baseline. Most completely rural counties with high rates included mining camps, lumbering camps, or fishing villages, and not farming areas. In addition to urban drift, urban birth and residence appear to be risk factors for developing severe mental illnesses. Psychological and biological explanations have both been proposed. However, recent studies reporting winter birth and urban birth or residence as synergistic risk factors favor the latter.
Substance misuse among people with schizophrenia is thought to be common and to adversely affect the outcome of the illness. The shortcomings of studies in this area include patient samples that are not epidemiologically-based, and methods for detecting substance misuse that have serious limitations. We investigated the frequency and severity of substance misuse among people with schizophrenia living in the community in London. Interviews were conducted with a community-based sample of 39 people with schizophrenia aged 35 years or less, living in Inner London. The assessments included ratings of psychopathology, movement disorders and substance misuse, and co-informant histories. Urine and hair specimens were analysed for a range of substances. Urine samples were collected from 37 patients and hair samples were provided by 36 patients. Comorbid substance misuse was reported or detected in 63% of the sample. The information elicited using a structured questionnaire for both informants and subjects represented an under-estimate of psychostimulant misuse and opiate misuse compared with the results obtained by hair or urine analysis. Hair analysis revealed that 12 (33%) of those patients providing samples had covertly abused amphetamines, opiates or cocaine in the previous 3 months. The study demonstrated that hair analysis is a well-tolerated, sensitive test for substance misuse. The technique has several advantages over questionnaires and urine analysis for clinical and research purposes. Further applications include the assessment of comorbid substance use in particular groups of patients with schizophrenia, such as during first-episode or psychotic relapse, or those with forensic problems or apparent resistance to treatment.
This study compared birth certificate data on the amount, timing, and adequacy of prenatal care with the same data abstracted from the prenatal clinic records of 2,032 women who attended a health department prenatal clinic in northeast Georgia from 1980 to 1988. Overall accuracy was poor. Only 14.3% (n = 291) of the records completely agreed on the total number of visits, while approximately 36% (n = 738) and 53% (n = 1,081) agreed within one visit and two visits, respectively. Complete agreement for month and trimester prenatal care began was 31.1% (n = 632) and 50.6% (n = 1,202), respectively. Because of the small geographic region included in the current study, the generalizability of these findings to other populations may be limited.
The relationships between several indices of psychosis proneness and bilateral electrodermal orienting were examined in a large group of normal subjects and a heterogeneous group of schizophrenic patients. In the normal group, the Cognitive Disorganisation scale was characterised by shorter latencies and more irregular patterns of responding that may indicate greater disinhibitory processing in the regulation of attentional mechanisms. The Unusual Experiences scale and paranoia (both measures of positive or 'active' schizotypy) were associated with a predominance of left hemisphere influences in normal female controls. High Introvertive Anhedonia scores predicted non-responding status in schizophrenic patients and hypo-responsivity in normal controls in support of some previous studies. Overall the results support the specificity and validity of different measures of psychosis proneness and the utility of psychophysiological investigation beyond the psychotic disorders themselves.
Radioiodinated methylene blue contains a mixture of components showing selective uptake in human pigmented melanoma, and it has potential for imaging and therapy. Nuclear magnetic resonance and mass spectroscopic studies show that the majority of the radioactivity (85%) is in the form of monoiodinated methylene blue, 4-iodo-3-methylamino-7-dimethylaminophenaza thionium chloride. The amino group ortho-to iodine has become demethylated to a mono-methylamino group. The remainder (15%) of the mixture is the doubly labelled 4,5-diiodo-3,7-bis(methylamino) phenazathionium chloride. The separated components show similar tumour selectivity in athymic mice bearing human pigmented melanomas.
We have sequenced a contiguous 284,495-bp segment of DNA extending from the terminal (TTAGGG)n repeats of the short arm of chromosome 16, providing a full description of the transition from telomeric through subtelomeric DNA to sequences that are unique to the chromosome. To complement and extend analysis of the primary sequence, we have characterized mRNA transcripts, patterns of DNA methylation and DNase I sensitivity. Together with previous data these studies describe in detail the structural and functional organization of a human telomeric region.
We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub-domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non-homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.
Completion of genetic and physical maps requires markers from the ends (telomeres) of every human chromosome. We have searched for short tandem repeats (microsatellites) in cosmid and P1 clones and generated 661 sequence-tagged sites (STS) from the terminal 300 kb of 31 human chromosome ends. PCR assays were successfully designed for 58 microsatellites and mapped both genetically and on radiation hybrids (RHs) to confirm their telomeric location. Sequence analysis revealed marked variation in sequence composition, consistent with the hypothesis that even very highly GC-rich chromosome bands (the T bands) are not homogenous. The STSs that we have generated will be a necessary resource for the construction of physical maps of these complex regions of the genome.
The theory that psychosis and dreaming share some common underlying mechanism finds support in the observation that chronic nightmare sufferers are at increased risk for psychopathology. We examined this connection in a large general population sample, administering a battery of psychosis proneness and other personality scales, together with a nightmare distress scale; participants also answered a single question on pleasurable mood associated with dreaming. In addition, they completed the Bem Sex Role Inventory, to reinvestigate previously observed gender differences in nightmare susceptibility. It was found that, among the psychosis proneness scales, the best predictor of nightmare distress was STA, a mostly cognitive measure of schizotypy; this was true even after allowing for a strong influence in the data of general neuroticism. Other aspects of psychosis proneness--e.g. anhedonia--were unrelated to nightmares. However, sex and sex role differences did make a significant contribution, self-confessed feminine females and masculine males reporting, respectively, the highest and lowest nightmare distress. For schizotypy it was further shown that relationships were not confined to the nightmare experience; high (STA) schizotypes also significantly more often reported enjoyable dreaming. It was concluded that a unifying theme explaining the data is the schizotype's greater imaginativeness, which can have both positive and negative expression in sleep and consciousness.
Because lower bone-mineral density is one potential physiological consequence of eating disorders and chronic alcohol misuse, the risk for osteoporosis may be compounded in women who have both conditions. This study investigated the frequency of eating disorders in 25 women who misuse alcohol and compared bone-mineral density between those with and without multiple disordered eating behaviors. Disordered eating behaviors were assessed through the EAT-26 (Eating Attitudes Test) and a structured interview addressing binge eating, purging, and other weight-control behaviors. Bone-mineral density was measured using dual energy x-ray densitometry. Although only one woman met the DSM-III-R criteria for a current eating disorder, 12% had past histories suggestive of anorexia nervosa and 40% had multiple disordered eating behaviors with bulimic features. Bone-mineral density of the femoral neck was 9.3% greater in women with multiple disordered eating behaviors (p < or = .05).
OBJECTIVE: To compare vibration perception thresholds (VPTs) obtained with two different instruments, a neurothesiometer and a vibratron, and to characterize variability of repeat measures and correlation with sural nerve conduction parameters. RESEARCH DESIGN AND METHODS: A total of 152 patients with diabetic peripheral neuropathy received electrodiagnostic evaluation and quantitative VPT testing with the Vibratron II and the Horwell Neurothesiometer. Of the patients, 42 returned for repeat nerve conduction studies and VPT testing with both types of equipment on three separate occasions. RESULTS: The variability of repeat testing for the vibratron was 34 and 31% in the right and left first toes, respectively. Variability for neurothesiometer was 8 and 6% for the right and left toes. This variability compares with that of sural nerve conduction velocity of 2% and that of sural nerve amplitude of 8% in this series of patients. CONCLUSIONS: We conclude that VPT determined with the neurothesiometer is less variable than with the vibratron and more reflective of peripheral nerve function. Our results indicate that the neurothesiometer can be used reliably in clinical research trials.