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Biomedical subjects

L Cooper

Publications and source records attributed to L Cooper.

At least 19 recordsLinked to original sources

Population awareness and control of hypertension and hypercholesterolemia. The Atherosclerosis Risk in Communities study.

BACKGROUND: A national program for hypertension detection and control was implemented in the 1970s, whereas a similar program for control of hypercholesterolemia has been implemented in recent years. We studied the levels of awareness, treatment, and control of these conditions in US population samples during a 3-year period (1987 to 1989). METHODS: The levels of awareness, treatment (by medication), and adequate control of hypertension (systolic blood pressure, > or = 140 mm Hg; diastolic blood pressure, > or = 90 mm Hg; or antihypertensive medication) and hypercholesterolemia (serum cholesterol level, > or = 6.21 mmol/L [> or = 240 mg/dL], or lipid-lowering medication) were studied among participants in the baseline examination of the Atherosclerosis Risk in Communities Study, including 15,739 individuals aged 45 to 64 years. RESULTS: Eighty-four percent of the hypertensive subjects and 42% of the hypercholesterolemic subjects were aware of their conditions. Overall, 50% of the hypertensive subjects and only 4% of the hypercholesterolemic subjects had their conditions both treated and controlled. Rates of hypertension prevalence, awareness, and control remained stable during the 3-year study period. Hypercholesterolemia prevalence decreased from 30% in 1987 to 25% in 1989; its awareness increased from 31% to 50% during the same period. Hypertensive women were more likely than hypertensive men to be aware and treated, whereas hypercholesterolemia awareness was higher in men than in women. Hypertension awareness was highest in black women, but black hypertensive subjects were less likely than whites to be treated and to have their hypertension controlled. Black hypercholesterolemic subjects were less likely to be either aware or treated. CONCLUSIONS: After the recent implementation of the National Cholesterol Education Program, the levels of awareness, treatment, and control of hypercholesterolemia are improving at a high rate, although they are still substantially lower than those for hypertension. Further improvement is necessary, particularly among certain population groups, such as blacks.

Age Distribution

Interplay between the human TCR/CD3 epsilon and the B-cell antigen receptor associated Ig-beta (B29).

T and B lymphocytes are characterized by the surface expression of highly variable antigen receptors called the T-cell (TCR) and B-cell (BCR) receptor. In both B and T cells, binding of antigen to their respective surface receptors results in transmembrane signaling which leads either to programmed cell death or to proliferation and differentiation. The human and murine TCR consist of the highly variable TCR alpha and beta or gamma and delta chains recognizing antigen and the non-covalently associated invariable CD3 complex (gamma, delta, epsilon) and zeta. The antigen-recognizing surface membrane-bound immunoglobulin (Ig) molecules on the surface of human and murine B cells are non-covalently associated with a heterodimeric protein complex of Ig-alpha (MB-1) and Ig-beta (B29). Like the CD3 complex associated with TCR the Ig-associated proteins are predicted to regulate the assembly and transport of the Ig complex to the cell surface and to couple membrane-bound Ig to intracellular signal transduction pathways. To gain more insight into structure/function relationships between CD3 proteins and Ig-alpha and Ig-beta, we transiently co-transfected pairs of expression vectors encoding either TCR/CD3 chains on the one hand and Ig-alpha or Ig-beta on the other into Cos cells. Thus we found a very strong interaction between CD3 epsilon and Ig-beta mediated by the extracellular domains. Experiments in which we could stain Jurkat T cells with soluble Ig-beta but not Ig-alpha protein indicated the recognition of CD3 epsilon by Ig-beta even in the context of the whole TCR/CD3 complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos.

Mutations in the human SRY-related gene, SOX9, located on chromosome 17, have recently been associated with the sex reversal and skeletal dysmorphology syndrome, campomelic dysplasia. In order to clarify the role of this gene in skeletal development, we have studied the expression of mouse Sox9 during embryogenesis. Sox9 is expressed predominantly in mesenchymal condensations throughout the embryo before and during the deposition of cartilage, consistent with a primary role in skeletal formation. Interspecific backcross mapping has localized mouse Sox9 to distal chromosome 11. The expression pattern and chromosomal location of Sox9 suggest that it may be the gene defective in the mouse skeletal mutant Tail-short, a potential animal model for campomelic dysplasia.

Amino Acid Sequence

Replacement of the active-site cysteine residues of DsbA, a protein required for disulfide bond formation in vivo.

DsbA is a periplasmic protein of Escherichia coli that was identified genetically as being involved in the formation of disulfide bonds in secreted proteins. Its active site contains one accessible and one buried cysteine residue, separated in the primary structure by only two other residues. These cysteine residues can form a very unstable disulfide bond that is 10(3)-fold more reactive toward thiols than normal. Moreover, the mixed disulfide between the accessible cysteine residue and glutathione is 10(4)-fold more reactive than normal. Site-directed mutagenesis was carried out to replace either one or both cysteine residues by serine. Cys30 is shown to be the accessible thiol, while Cys33 is shielded from the solvent. Even though the thiol group of Cys30 is exposed and reactive, it formed a very unstable mixed disulfide with glutathione. This disulfide bond was 2.17 +/- 0.02 kcal mol-1 less stable in the native conformation than when DsbA was unfolded. If the native conformation destabilizes the mixed disulfide, the mixed disulfide must destabilize the folded conformation to the same extent. This was confirmed by demonstrating that the folded conformation of the mixed disulfide form of the mutant DsbA was 2.7 +/- 0.9 kcal mol-1 less stable than that of the reduced form; these stability effects originated almost exclusively in the folded conformation. Replacing the cysteine residues by serine destabilized the folded conformation of the reduced protein to varying extents. This suggests that the thiol groups are involved in interactions that stabilize the folded conformation, which would cause any disulfide bonds, either inter- or intramolecular, that involve these groups to be unstable.

Base Sequence

DNA probes for identifying the members of the Anopheles punctulatus complex in Papua New Guinea.

Genomic DNA probes were made for five members of the Anopheles punctulatus complex of mosquitoes found in Papua New Guinea. Specific DNA probes were developed for An. punctulatus, An. koliensis, and three sibling species, An. farauti No. 4, An. farauti No. 5, and An. farauti No. 6, by differentially screening total genomic DNA libraries of individual species and sibling species with homologous DNA against heterologous DNA labeled with 32P. Probes ranged from 273 to 630 bp. Identification of species can be made from squash or dot blots using only a segment of the mosquito (i.e, head, thorax, abdomen, or even legs), allowing for concurrent analysis of the remainder of the mosquito for other epidemiologic characteristics.

Animals

On the biosynthesis of bovine pancreatic trypsin inhibitor (BPTI). Structure, processing, folding and disulphide bond formation of the precursor in vitro and in microsomes.

The natural gene for bovine pancreatic trypsin inhibitor (BPTI) was expressed by in vitro transcription/translation systems as the 100-residue pre-proBPTI, with a signal peptide for translocation into the endoplasmic reticulum. Expression in the presence of microsomes defined the site of co-translational cleavage of the signal peptide. The resulting proBPTI in the microsomes consists of the 58 residues of mature BPTI, plus an additional 13 residues at the N terminus, including a cysteine residue at position -10, and seven residues at the C terminus. ProBPTI remained in the unfolded, reduced form within microsomes when synthesized under reducing conditions, but folded and formed disulphide bonds rapidly when the disulphide form of glutathione was added. Complete folding could occur within about one minute, even when residue Cys10 was replaced by Ser. The structure of proBPTI was determined by circular dichroism and two-dimensional NMR and found to be that of mature BPTI with flexible extensions on both termini. Its inhibition of the activity of alpha-chymotrypsin was indistinguishable from that of the mature protein. The extensions of the precursor appeared to play only very minor roles in refolding in vitro under conditions where folding and disulphide bond formation are coupled. Under pH and redox conditions thought to reflect those in vivo, complete folding and disulphide bond formation required several hours. Addition of protein disulphide isomerase to in vitro folding experiments caused substantial and similar increases in the rate of formation of the fully folded state for both mature BPTI and proBPTI; the half time for folding to the native state was reduced to approximately two minutes, which is comparable to that occurring in microsomes. The absence of substantial effects of the N and C-terminal extensions on the protein structure, inhibitor activity and refolding leaves their functional roles to be discovered.

Amino Acid Sequence

Behavioral problems among twins.

Despite the frequency of multiple births, little information is available to assist parents and health professionals in the identification and management of behavior problems in multiple-birth siblings. Three case reports are presented that describe quarreling, aggression, and feeding problems among twins. To develop intervention strategies most appropriate for the problem behavior, it is important to determine whether (1) parents are able to effectively implement the intervention strategy, (2) behavior is isolated to one sibling, and (3) different reasons are responsible for similar behavior in siblings. Structured observations were used to determine whether the undesired behavior occurred to escape nonpreferred activities, gain access to preferred activities, or obtain parental attention. The cases provide a framework to facilitate the identification and management of common behavior problems occurring among multiple-birth siblings.

Child Behavior Disorders

Comparison of diazepam with progestin for effectiveness in suppression of urine spraying behavior in cats.

The most common treatment for urine spraying and marking in cats has been administration of long-acting progestins. Treatment with diazepam has recently been gaining favor, particularly because of reported adverse effects of progestins. Results of a clinical trial involving 20 cats indicated that diazepam was effective in eliminating or markedly reducing spraying in 11 (55%) of them. However, most cats required continuous treatment, or at least intermittent treatment, when spraying recurred. The physiologic and behavioral dependency of cats on diazepam, which presumably develops over the course of administration, may contribute to the tendency for spraying to recur once diazepam treatment is discontinued. Using data from previously published findings on progestin administration, plus additional cases, it was documented that a significantly (P less than 0.05) higher percentage of males than females responded favorably. Although the number of cases was not sufficient for a statistical comparison of diazepam vs progestin treatment with regard to male vs female, possible gender difference in the effectiveness of diazepam was not indicated.

Animals

Cloning and sequencing of the cDNA encoding the human homologue of the murine immunoglobulin-associated protein B29.

Membrane-bound immunoglobulins (Ig) on the surface of murine B cells are noncovalently associated with a heterodimeric protein complex of MB-1 and B29 (also called Ig-alpha and Ig-beta). The Ig-associated proteins are predicted to regulate the assembly and transport of the Ig complex to the cell surface and to couple membrane-bound Ig to intracellular signal transduction pathways. We have isolated and sequenced a full-length cDNA clone encoding the human homologue of the B29 protein. The predicted amino acid sequence was compared to its murine counterpart, to MB-1 and to the human T cell receptor (TcR)-associated CD3 proteins. The alignment of the human B29 protein with its murine counterpart revealed 90% homology in the C-terminal portion comprising the cytoplasmic tails, the transmembrane regions and the adjacent 26 amino acids of the extracellular regions. Only 59% homology was found in the rest of the Ig-like extracellular domains. The high degree of conservation observed for the C-terminal amino acids suggested that these domains of the proteins play important functional roles for the Ig complex. Indicative of this was the conservation of the antigen receptor tail motif D-(X)7-E/D-(X)2-Y-(X)2-L-(X)7-Y-(X)2-L/I which is thought to be a component of signal transduction pathways. This motif is also found in the human and murine MB-1 proteins as well as in the TcR-associated CD3 molecules. Further regions of homology between B29, MB-1 and the CD3 proteins included extracellular residues which were predicted to maintain the Ig-like structure, and hydrophilic residues within the transmembrane regions which may be utilized during the intracellular assembly and transport of the oligomeric Ig/MB-1/B29 or TcR/CD3 complexes. Thus the similarities found between B29, MB-1 and the CD3 proteins suggest conserved functions for both the Ig- and TcR-associated proteins.

Amino Acid Sequence

The Anopheles punctulatus complex: DNA probes for identifying the Australian species using isotopic, chromogenic, and chemiluminescence detection systems.

Isotopic and enzyme-labeled species-specific DNA probes were made for the three known members of the Anopheles punctulatus complex of mosquitoes in Australia (Anopheles farauti Nos. 1, 2, and 3). Species-specific probes were selected by screening total genomic libraries made from the DNA of individual species with 32P-labeled DNA of homologous and heterologous mosquito species. The 32P-labeled probes for A. farauti Nos. 1 and 2 can detect less than 0.2 ng of DNA while the 32P-labeled probe for A. farauti No. 3 has a sensitivity of 1.25 ng of DNA. Probes were then enzyme labeled for chromogenic and chemiluminescence detection and compared to isotopic detection using 32P-labeled probes. Sequences of the probe repeat regions are presented. Species identifications can be made from dot blots or squashes of freshly killed mosquitoes or mosquitoes stored frozen, dried, and held at room temperature or fixed in isopropanol or ethanol with isotopic, chromogenic, or chemiluminescence detection systems. The use of nonisotopic detection systems will enable laboratories with minimal facilities to identify important regional vectors.

Alkaline Phosphatase

Adult discharge planning and nursing home placement: a study of risk factors for quality assurance.

OBJECTIVE: A study of two large groups of patients was conducted in a large general hospital, comparing the admission characteristics of those referred to nursing homes and those returning home, to identify factors on admission that would facilitate more rapid discharge planning and placement. METHOD: Discharge planning at the Royal Brisbane Hospital was analysed over 12 months, comparing the admission characteristics of 191 patients placed in nursing homes with 444 patients returning home. RESULTS: Referral of patients to social workers was delayed and poorly co-ordinated, leading to prolongation of the discharge process or placement for nursing home patients. The data indicate that the process can be expedited by attention to readily recognizable factors already present on admission.

Activities of Daily Living

A component analysis of functional communication training across three topographies of severe behavior problems.

We evaluated the separate treatment components of a functional communication training program for 3 severely handicapped persons who each displayed different topographies of aberrant behavior. Following a functional analysis of maintaining conditions for inappropriate behavior (self-injury, stereotypy, aggression), each participant was trained to emit a communicative response that functioned to solicit reinforcement. For 2 participants, consequences (time-out or graduated guidance) for inappropriate behavior were also included. Treatment continued until the participants emitted the communicative response independently and no occurrences of inappropriate behavior were observed for at least two sessions. Following treatment, the separate contributions of the treatment components for communicative responding and for inappropriate behavior were evaluated with a reversal design. The results indicated that both sets of treatment components were necessary for maximal control over aberrant behavior. These results are discussed in relation to the efficiency, history, and control over reinforcement of both appropriate and inappropriate responses.

Behavior Therapy

Use of an intraaortic balloon pump as a pneumatic ventricular assist device controller.

Using a circulatory analogue, we investigated sequentially the performance of a dedicated ventricular assist device driver and an intraaortic balloon pump when driving a pneumatic ventricular assist device. Each drive device was compared under identical pumping conditions at rates of 40 to 120 cycles/min against two resistances. Our preliminary study showed that a modified intraaortic balloon pump could drive a pneumatic ventricular assist device as effectively as its dedicated driver. The necessary modifications to and possible further development of the intraaortic balloon in this role are discussed.

Assisted Circulation