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Biomedical subjects

S Cook

Publications and source records attributed to S Cook.

At least 37 records · Page 2Linked to original sources
PubMed1990

Interventional cardiovascular therapy by laser and thermal angioplasty.

The advent of balloon angioplasty as a clinical device crystallized the concept of nonsurgical revascularization. The problems of restenosis, diffuse disease, and total occlusions persist despite the demonstrated efficacy of balloon angioplasty. During the past 5 years, a variety of laser devices and catheter designs have demonstrated usefulness in the treatment of peripheral vascular disease. Initial success rates of 70-90% have been reported in occluded femoropopliteal arteries. Further clinical trials are warranted to compare the relative efficacy of these devices with each other and conventional therapies. Thermal ablative devices have not yet shown great promise for treatment of coronary disease. Modified versions of these devices as well as nonthermally acting excimer lasers are promising as clinical tools for enhancing our ability to nonsurgically revascularize patients, and trials with these devices are now underway.

Angiography↗
PubMed1989

Cytotoxicity of gelonin and its conjugates with antibodies is determined by the extent of their endocytosis.

Conjugates of the single-chain ribosome-inactivating protein gelonin with ligands that bind to cell surface molecules vary greatly in their cytotoxicity. Conjugates that are not endocytosed after binding to cells exhibit low cytotoxicity similar to that of free gelonin, while conjugates that are endocytosed demonstrate enhanced cytotoxicity relative to free gelonin. However, the number of internalized gelonin molecules needed to intoxicate cells to the same degree has been found to be similar for all conjugates and for free gelonin. The intracellular concentration of gelonin has to be between 2,000-10,000 molecules/cells to achieve a surviving fraction of 0.37. Our studies revealed the presence of three distinct categories of cell surface molecules, those that are efficient in mediating endocytosis of immunotoxins, those that are only moderately efficient, and those that seem not to cause internalization of bound immunotoxins.

Animals↗
PubMed1989

Membrane specializations associated with the acrosomal complex of sea urchin sperm as revealed by immunocytochemistry and freeze fracture replication.

Observations, employing freeze fracture replication and electron microscopic immunochemistry, have been carried out to determine structural correlations of the plasma membrane domain occupied by a 210 kDa protein involved in the acrosomal reaction of sea urchin sperm and recognized by the monoclonal antibody, J10/14 (Trimmer et al.: Cell 40:697-703, 1985; Proceedings of the National Academy of Sciences of the United States of America 83: 9055-9059, 1986). Immunogold-J10/14 staining of acrosome-intact sperm was intense along the flagellum and a narrow collar just posterior to the sperm apex that surrounded the acrosomal complex (acrosomal vesicle and subjacent anterior nuclear fossa containing g-actin). Counts of gold particles revealed a density (average number of particles/micron2 of surface area) eightfold greater along the plasma membrane associated with the acrosomal complex than membrane delimiting the remainder of the sperm head. The collar of J10/14 staining was isomorphic with a dense aggregation of intramembranous particles in the P-face of the plasma membrane and a thin cytoplasmic region that surrounded the acrosomal complex. In acrosome-reacted sperm, intense J10/14 staining was distributed along the flagellum and sperm head; prominent anterior staining was not apparent in all specimens. The density of gold particles associated with plasma membrane delimiting components of the former acrosomal complex, nucleus and mitochondrion, as well as the total average number of particles along the entire sperm surface, were increased in sperm acrosome-reacted with A-23187. Concomitant with this change in staining was the disappearance/reduction of the collars of intramembranous particles and cytoplasm. These observations indicate that plasma membrane components (210 kDa protein and intramembranous particles) and the collar of cytoplasm which are associated with the acrosomal complex are functionally, as well as structurally related. Analyses of particle density distributions along acrosome- and non-acrosome-reacted sperm suggest that the different staining patterns observed may be brought about by the recognition of cryptic sites at the time of the acrosomal reaction.

Acrosome↗
PubMed1988

Molecular orientation of immunoglobulin G at high concentration on an ion-exchange sorbent.

The change of molecular orientation of IgG, bound on a strong-anion-exchange surface, was studied using a generalization of the stoichiometric displacement model, over the entire range of protein adsorption isotherms. The Z number was found to decrease with increasing stationary phase protein concentration, approaching a limiting value. The analogy of the multiple equilibria model within highly cooperative identical binding sites was suggested as a possible way to evaluate the observed change in Z number with the protein concentration.

Adsorption↗
PubMed1988

Replacements of Pro86 in phage T4 lysozyme extend an alpha-helix but do not alter protein stability.

To investigate the relation between protein stability and the predicted stabilities of individual secondary structural elements, residue Pro86 in an alpha-helix in phage T4 lysozyme was replaced by ten different amino acids. The x-ray crystal structures of seven of the mutant lysozymes were determined at high resolution. In each case, replacement of the proline resulted in the formation of an extended alpha-helix. This involves a large conformational change in residues 81 to 83 and smaller shifts that extend 20 angstroms across the protein surface. Unexpectedly, all ten amino acid substitutions marginally reduce protein thermostability. This insensitivity of stability to the amino acid at position 86 is not simply explained by statistical and thermodynamic criteria for helical propensity. The observed conformational changes illustrate a general mechanism by which proteins can tolerate mutations.

Enzyme Stability↗
PubMed1988

A mutation in the PA protein gene of cold-adapted B/Ann Arbor/1/66 influenza virus associated with reversion of temperature sensitivity and attenuated virulence.

Reassortant SG3 inherits only the acidic polymerase (PA) protein gene from the cold-adapted B/AA/1/66 influenza virus (ca B/AA/1/66) and all remaining genes from a virulent, wild-type virus. This reassortant demonstrates attenuated virulence in ferrets and expresses a ts phenotype characteristic of the ca parent. During virulence evaluation of SG3, a virulent, non-ts revertant virus (designated SG3rFL) was isolated from the lungs of one ferret. In order to determine whether the reversion of SG3 resulted from mutation of the PA gene and/or as the result of extragenic supressor mutations, the revertant PA gene of SG3rFL was transferred to a reassortant (SG3r) inheriting only the revertant PA gene from SG3rFL and all remaining genes from SG3. Reassortant SG3r was non-ts and virulent, indicating that mutation of the PA gene was sufficient for the reversion of the ts and attenuation phenotypes expressed by SG3rFL. The nucleotide and predicted amino acid sequences of the SG3rFL PA gene were determined and compared to those of wt and ca B/AA/1/66. The predicted PA proteins of wt and ca B/AA/1/66 are known to differ by six amino acid substitutions including a valine to methionine substitution at residue 431. The PA proteins of ca B/AA/1/66 and SG3rFL were distinguished by only the single amino acid substitution of methionine to isoluecine also occurring at residue 431. Thus, the methionine residue was implicated in the attenuation of ca B/AA/1/66 and its reassortants. The hydropathic properties of valine, isoleucine, and methionine suggested that reversion involved the restoration of hydrophobic character at this site.

Amino Acid Sequence↗
PubMed1988

Intramuscular ceftriaxone in home parenteral therapy.

Ceftriaxone administered via the intramuscular route was evaluated as home parenteral therapy for 31 patients with a variety of serious but stable infections. Cure was achieved in 30 of the patients. When lidocaine was used for reconstitution of ceftriaxone, the intramuscular route was well tolerated by all patients.

Ceftriaxone↗
PubMed1988

Osteoporotic correlates of alcoholism in young males.

A group of 22 white males (ages, 28 to 40 years) with histories of chronic alcohol abuse ranging from 1 to 21 years were evaluated for trabecular bone mineral density in the left femoral neck area. A group of age and weight-matched white males with no history of alcoholism served as controls. All participants completed medical history questionnaires regarding fracture history, dietary habits, medications, and physical activity. Singh femoral trabecular indices also were measured for the alcoholic participants. Analysis of bone mineral data as measured by dual photon absorptiometry revealed no statistically significant reduction in the bone mineral densities of the alcoholic group when compared to the controls. No differences were seen in the areas of the femoral neck, Ward's triangle, and greater trochanter. Duration of alcoholism also was not correlated with the degree of osteopenia. Singh index measurements of right and left femoral heads were compared and revealed no significant differences within individual patients. Left femoral Singh index values averaged 5.5 (range, 4 to 6) for the alcoholic group and were not indicative of decreased bone mineral density. It is concluded from this study that chronic alcoholism associated with heavy smoking most likely has a debilitating effect on the trabecular bone density of white males, yet clinical and radiographic evidence is not widely manifested in men under the age of 40 years.

Adult↗
PubMed1988

Bilateral elastofibroma dorsi.

Elastofibroma, a rare, noncapsulated, benign entity (pseudotumor), is characterized by the proliferation of fibrous tissue with elastin and scattered islands of adipose tissue that occurs most often in the infrascapular area of elderly women. We report on a 44-year-old man with bilateral infrascapular elastofibromas.

Fibroma↗
PubMed1987

Serum antibodies to HTLV-I in human demyelinating disease.

Serum HTLV-I antibodies were measured in 17 MS patients and 2 closely matched control groups by 2 different independent assays. A highly sensitive particle agglutination test was used to detect HTLV-I core protein antigens and an immunoblot assay with E. coli-expressed P21E transmembrane protein was employed to detect antibodies to HTLV-I evelope antigens. No serologic evidence of prior HTLV-I infection in our population of multiple sclerosis (MS) or Guillain-Barré Syndrome (GBS) patients was found.

Adult↗
PubMed1987

Molecular cloning of 99% of measles virus genome, positive identification of 5' end clones, and mapping of the L gene region.

Molecular probes specific for paramyxovirus 3' and 5' end sequences are essential for studying viral transcription and replication and the role of defective interfering particles in these processes. We have constructed from measles virus genomic RNA an ordered series of overlapping clones containing over 99% of measles virus genetic information. Clones corresponding to the 3' and 5' ends of the genome were identified by means of a probe made from 'capped' genomic RNA, and their location was confirmed by primer extension experiments. Clones representing the N, P/C, M, F, and H genes were identified by reference to previously characterized clones, and their positions in the genome were defined by restriction analysis and S1 nuclease mapping of intercistronic clones. The L gene region was characterized by site-to-site restriction mapping and measured as 6,550 nucleotides in length.

Chromosome Mapping↗
PubMed1986

Bile acids and the intestinal kallikrein-kinin system.

We have measured concentrations of tissue kallikrein-like amidase (TKLA) in blood-free rat gastrointestinal tissue. TKLA was present in the gut wall from the stomach to the rectum with concentration peaks in the duodenum and caecum. When rats, fasted for 24 hr were compared with normally fed animals, the mean fasted TKLA levels rose significantly in the duodenum and proximal and distal colons and fell in the caecum. No other tissues showed concentration changes. Sodium chenodeoxycholate and other bile acids have biological actions on the rat intestinal wall which are similar to those produced by the kallikrein-kinin system. We have previously reported that bile acids released TKLA from the rat colon wall. This TKLA was totally inhibited by aprotinin. We now report that intraluminal sodium chenodeoxycholate (30 mM) increases both colonic motility and colonic mucosal leakage. These increases are largely blocked by aprotinin. The ability of intraluminal sodium taurochenodeoxycholate to increase vascular leakage in the rat stomach and colon was parallelled by its ability to release TKLA from these issues. Our results are compatible with the mediation of these biological actions of the tested bile acids via activation of a serine proteinase, possibly tissue kallikrein.

Animals↗
PubMed1986

Interaction of the monoclonal antibodies alpha IR-1 and alpha IR-3 with insulin and somatomedin-C receptors.

alpha IR-3, a monoclonal antibody that interacts with the somatomedin-C receptor, inhibited the binding of somatomedin-C, but not of insulin, to human placental membranes and intact IM-9 cells. alpha IR-1, a monoclonal antibody that interacts with the insulin receptor, did not inhibit the binding of either hormone. Inhibition of somatomedin-C binding by alpha IR-3 was mainly due to a decrease in its affinity. 125I-Labeled alpha IR-3 bound specifically to placental membranes and intact IM-9 cells and was inhibited by concentrations of unlabeled alpha IR-3 that were lower than those required to inhibit somatomedin-C binding. [125I]alpha IR-3 binding was also inhibited by somatomedin-C and insulin, but only at very high concentrations. A410, a rabbit antiserum that reacts with both receptors for insulin and somatomedin-C, also inhibited labeled alpha IR-3 binding. alpha IR-I did not. These results help to define the epitopes with which these antibodies interact.

Animals↗