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Biomedical subjects

S Cook

Publications and source records attributed to S Cook.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1984

Effect of high-dose intravenous steroid administration on contrast-enhancing computed tomographic scan lesions in multiple sclerosis.

Six consecutive patients with multiple sclerosis and lesions contrast enhancing on computed tomographic scan were treated with high-dose intravenous infusions of methylprednisolone. Double-dose delayed computed tomographic scans were repeated at varying intervals during corticosteroid treatment. Contrast enhancement of sclerotic plaques was reduced or eliminated within as little as 8 hours after the first infusion. Rapid associated partial clinical improvement was noted in four patients with recent exacerbations of disease activity. Similar attenuation of contrast-enhancing plaques and clinical improvement were less predictable following oral corticosteroid therapy in conventional dosage. These studies suggest that the dose, route of administration, and duration of corticosteroid therapy in multiple sclerosis may partially determine the effect of treatment.

Adult↗
PubMed1982

Ethnic group response to preventive health education.

Using the ratio of preventive visits to episodic visits as an index of health care utilization in response to an education campaign which emphasized the value of prevention, we analyzed the response of white, Mexican-American, and black subjects in a community health center. We found that: (1) whites make a relatively larger proportion of preventive care visits than Mexican-Americans, who made proportionately more preventive health care visits than blacks. The difference between whites and blacks was statistically significant (p less than .05). (2) When socioeconomic levels were held constant, as measured by insurance categories, no ethnic differences in preventive vs episodic health care visits were found. (3) On the other hand significant differences in such health care behavior emerged when indices of family structure and employment were isolated. Mexican-Americans seek proportionately less preventive care in families in which one parent is absent and no adult is employed. In contrast, blacks seek proportionately less preventive care in families in which both parents are present at at least one adult is employed.

Black or African American↗