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Biomedical subjects

C W Smith

Publications and source records attributed to C W Smith.

At least 289 records · Page 16Linked to original sources
PubMed1988

Synthesis and renin inhibitory activity of angiotensinogen analogues having dehydrostatine, Leu psi [CH2S]Val, or Leu psi [CH2SO]Val at the P1-P1' cleavage site.

The synthesis and in vitro renin inhibitory potencies of angiotensinogen (ANG) analogues having amide (CONH) bond replacements at P1-P1', the Leu-Val cleavage site, corresponding to Leu psi[CH2SO]Val, and the trans olefinic analogue of statine (Sta), 4(S)-amino-6-methyl-2(E)-heptenoic acid (dehydrostatine, Dhs), are reported. These are compared to P1-P1' Leu psi[CH2NH]Val-, Sta-, or Phe-Phe-substituted analogues of the same template. The Dhs pseudodipeptide was found to be an adequate mimic of a trans CONH bond and gave a peptide, H-Pro-His-Pro-Phe-His-Dhs-Ile-His-D-Lys-OH, approximately equal in potency to a Phe-Phe-containing inhibitor, but 200-fold less potent than its Sta-substituted congener. That the enhanced potency of the Sta-containing peptide most likely depends on hydrogen bonding as well as tetrahedral geometry is indicated by the 50-100-fold lower potency of the tetrahedral Leu psi[CH2S]Val and Leu psi[CH2SO]Val analogues as compared to the Leu psi[CH2NH]Val-containing congener.

Amino Acids↗
PubMed1988

Management of Alzheimer's disease. A family affair.

The various approaches to the patient with Alzheimer's disease are receiving much attention, but relatively little has been written about the important role physicians can serve in helping the patient's family deal with the disease. In managing Alzheimer's disease, the physician's relationship with family members may be as important as or even more important than his or her relationship with the patient. Establishing and maintaining a successful relationship involve early assessment of family function, periodic home visits, coordination of available community resources, regular assessment of caregivers' coping skills, and regular discussions about the limits of home care and the possibility of placement in a nursing home. When nursing home care is chosen, the physician can, by continuing his or her involvement, help assure provision of the highest quality care possible.

Adaptation, Psychological↗
PubMed1988

Mapping an antibody-binding site and a T-cell-stimulating site on the 1A protein of respiratory syncytial virus.

A synthetic peptide modeled on residues 45 to 60 of the 1A protein of respiratory syncytial (RS) virus [1A(45-60)] was constructed and used for immunization of mice and rabbits. The immunoglobulin G fraction of the resulting rabbit antibody, purified on protein A-Sepharose, immunoprecipitated from RS-infected HEp-2 cells a protein with a molecular size of approximately 9.5 kilodaltons, which corresponds to the previously published molecular size of the 1A protein (Y. T. Huang, P. L. Collins, and G. W. Wertz, Virus Res. 2:157-173, 1985). To investigate the T-cell-inducing properties of 1A(45-60), six strains of mice were immunized and their popliteal lymph node cells were tested for proliferation upon restimulation with peptide in vitro. The lymph node cells of all six strains of mice were responsive to restimulation with 1A(45-60) and showed high- and low-responder strain variation. These peptide-primed lymph node cells also proliferated upon in vitro restimulation with RS virus-infected cells. Correlation of proliferation with interleukin 2 production suggested that the responding lymphocytes were T-helper cells. The antibody-binding and T-cell-stimulating sites of 1A were mapped by constructing a series of overlapping synthetic peptides and testing each for ability to react with antiserum prepared by immunization of BALB/C mice with free peptide 1A(45-60) or for ability to restimulate proliferation in 1A(45-60)-primed lymph node cells of BALB/C mice. Human antibody, obtained during confirmed RS virus infection, was similarly tested with the truncated peptides. Antibody-binding activity was reduced after truncation from the carboxy terminus, and a binding site was mapped to residues 51 through 60, the smallest peptide tested. T-cell-stimulating activity in mice was relatively resistant to truncation from the carboxy terminus and sensitive to truncation from the amino terminus. The smallest region which retained significant T-cell-stimulating activity mapped to residues 46 through 56. However, addition of the naturally occurring Cys at residue 45 and extension of the C terminus to residue 62 resulted in maximum T-cell-stimulating activity of the peptide. These data define both a T-cell epitope and a B-cell epitope of the 1A protein of RS virus and suggest that the carboxy terminus of 1A contains a B-cell epitope, involving residues 51 through 60, which is recognized during natural human infection.

Amino Acid Sequence↗
PubMed1988

The rat alpha-tropomyosin gene generates a minimum of six different mRNAs coding for striated, smooth, and nonmuscle isoforms by alternative splicing.

Tropomyosin (TM), a ubiquitous protein, is a component of the contractile apparatus of all cells. In nonmuscle cells, it is found in stress fibers, while in sarcomeric and nonsarcomeric muscle, it is a component of the thin filament. Several different TM isoforms specific for nonmuscle cells and different types of muscle cell have been described. As for other contractile proteins, it was assumed that smooth, striated, and nonmuscle isoforms were each encoded by different sets of genes. Through the use of S1 nuclease mapping, RNA blots, and 5' extension analyses, we showed that the rat alpha-TM gene, whose expression was until now considered to be restricted to muscle cells, generates many different tissue-specific isoforms. The promoter of the gene appears to be very similar to other housekeeping promoters in both its pattern of utilization, being active in most cell types, and its lack of any canonical sequence elements. The rat alpha-TM gene is split into at least 13 exons, 7 of which are alternatively spliced in a tissue-specific manner. This gene arrangement, which also includes two different 3' ends, generates a minimum of six different mRNAs each with the capacity to code for a different protein. These distinct TM isoforms are expressed specifically in nonmuscle and smooth and striated (cardiac and skeletal) muscle cells. The tissue-specific expression and developmental regulation of these isoforms is, therefore, produced by alternative mRNA processing. Moreover, structural and sequence comparisons among TM genes from different phyla suggest that alternative splicing is evolutionarily a very old event that played an important role in gene evolution and might have appeared concomitantly with or even before constitutive splicing.

Amino Acid Sequence↗
PubMed1988

Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration.

Human neutrophil (PMN) attachment to human umbilical vein endothelial cells (HUVEC) was evaluated in vitro using two MAbs, R6-5-D6 and RR1/1, that recognize intercellular adhesion molecule-1 (ICAM-1), and one MAb, TS1/18, that recognizes CD18. Pretreatment of the HUVEC with anti-ICAM-1 MAbs produced greater than 50% inhibition of attachment to HUVEC, and IL-1 (0.5 U/ml)- or lipopolysaccharide (LPS) (10 ng/ml)-stimulated HUVEC, and greater than 99% inhibition of f-Met-Leu-Phe (0.5 nM) enhanced adherence. Anti-ICAM-1 MAbs also inhibited by greater than 85% the transendothelial migration induced by 4-h IL-1 (0.5 U/ml) and LPS (10 ng/ml) activation of the HUVEC. That these effects involved a CD18-dependent mechanism is supported by the following results: pretreatment of PMN with TS1/18 produced the same degree of inhibition of attachment and migration as seen with R6-5-D6. In addition, the use of both MAbs together did not further increase the inhibition of cell attachment to stimulated HUVEC. The attachment of PMN from patients with CD18 deficiency to stimulated HUVEC was not reduced by R6-5-D6, and both R6-5-D6 and TS1/18 revealed the same time course for appearance and disappearance of an adherence component on stimulated HUVEC not blocked by either MAb. These results demonstrate that attachment and transendothelial migration of PMN in vitro depend substantially on both CD18 on the PMN and ICAM-1 on the endothelial cell.

Antibodies, Monoclonal↗
PubMed1988

Endovascular papillary angioendothelioma in the spleen.

Endovascular papillary angioendothelioma is a rare vascular neoplasm originally described as involving the skin and subcutaneous tissues. No case has been reported to involve the spleen, although structurally similar splenic neoplasms have been reported under different names. A 5-year-old boy presented with isolated splenomegaly and was found to have endovascular papillary angioendothelioma of the spleen. Studies supported the suggestion that the endovascular papillary angioendothelioma manifests focal "high" endothelial differentiation.

Child, Preschool↗
PubMed1988

Hamstring release for knee flexion contracture in spastic adults.

Thirty adults (17 male and 13 female patients) with spastic disorders were treated by hamstring releases of 46 extremities. The diagnoses were stroke, traumatic brain injury, spinal cord injury, multiple sclerosis, and anoxia. The mean age at surgery was 38.6 years. Three extremities had partial release of the hamstring tendons behind the knee; the remaining 43 extremities had a complete release. The average position of the knee was 61.4 degrees of flexion preoperatively and 6 degrees postoperatively. The follow-up period averaged 21.3 months. Preoperatively, 87% of patients were nonambulatory. Following hamstring release 43% became ambulatory and 17% had gained the ability to transfer. Complications included two stroke patients with severe peripheral vascular disease; one developed a large nonhealing sore of the ankle and the other developed gangrene of the foot. Both patients required amputation. Three other patients developed recurrent flexion contractures that have since been rereleased with good results.

Adult↗
PubMed1987

The mechanism of Ca2+ regulation of vascular smooth muscle thin filaments by caldesmon and calmodulin.

The interactions of vascular smooth muscle caldesmon with actin, tropomyosin, and calmodulin were determined under conditions in which the four proteins can form reconstituted Ca2+-sensitive smooth muscle thin filaments. Caldesmon bound to actin in a complex fashion with high affinity sites (K = 10(7) M-1) saturating at a stoichiometry of 1 per 28 actins, and lower affinity sites at 1 per 7 actins. The affinity of binding was increased in the presence of tropomyosin, and this could be attributed to a direct interaction between caldesmon and tropomyosin which was demonstrated using caldesmon cross-linked to Sepharose. In the presence of tropomyosin, occupancy of the high affinity sites was associated with inhibition of actin-activated myosin MgATPase activity. Caldesmon was found to bind to calmodulin in the presence of Ca2+, with an affinity of 10(6) M-1. The binding of Ca2+ X calmodulin to caldesmon was associated with the neutralization of inhibition of actin-tropomyosin. Ca2+ X calmodulin binding reduced but did not abolish the binding of caldesmon to actin-tropomyosin. From this data we have proposed a model for smooth muscle thin filaments in which Ca2+ regulates activity by converting the inhibited actin-tropomyosin-caldesmon complex to the active complexes, actin-tropomyosin-caldesmon-calmodulin X Ca2+ and actin-tropomyosin.

Actin Cytoskeleton↗
PubMed1987

5-Acyl-3-substituted-benzofuran-2(3H)-ones as potential antiinflammatory agents.

A series of 5-acyl-3-substituted-benzofuran-2(3H)-ones and their respective ring-opened o-hydroxy acids were synthesized. The antiinflammatory activity was evaluated in terms of their ability to improve adjuvant induced arthritis in rats. Their effect on the production of both cyclooxygenase (CO) and lipoxygenase (LO) metabolites of arachidonic acid in guinea pig peritoneal polymorphonuclear neutrophils (PMNs) was also examined. No correlation between the antiinflammatory activity and increasing stability of the lactones could be found. The degree of activity in general shown by the benzofuranones was similar to that of their corresponding o-hydroxy acids. This, coupled with the evidence from studies on opening of the lactone ring, suggests an in vivo transformation of the former into the latter. Benzofuranones displayed a dual inhibition of CO and LO products, while a moderate reduction in CO metabolites was shown by their acids.

Animals↗
PubMed1987

Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action.

A peptide inhibitor, having the sequence D-His-Pro-Phe-His-Phe psi [CH2-NH]Phe-Val-Tyr, with a reduced bond between the two adjacent phenylalanines, has been diffused into crystals of the aspartic proteinase from Rhizopus chinensis (rhizopuspepsin, EC 3.4.23.6). X-ray diffraction data to 1.8-A resolution have been collected on the complex, which has been subjected to restrained least-squares refinement to an R-factor (R equals the sum of the absolute value of the difference between the observed and calculated structure factor amplitudes divided by the sum of the observed structure factor amplitudes) of 14.7%. The inhibitor lies within the major groove of the enzyme and is clearly defined with the exception of the amino-terminal D-histidine and the carboxyl-terminal tyrosine. The reduced peptide bond is located in the active site with close contacts to the two catalytic aspartyl groups. The active-site water molecule that is held between the two carboxyl groups is displaced by the inhibitor, as are a number of other water molecules seen in the binding groove of the native enzyme. A mechanism of action for this class of enzymes is proposed from these results.

Aspartic Acid Endopeptidases↗
PubMed1987

Candidacidal activity of macrophages from three mouse strains as demonstrated by a new method: neutral red staining.

A new method for assessing the candidacidal activity of macrophages utilizing neutral red stain gave results comparable to well established vital staining methods, methylene blue and acridine orange, and to the absence of germ tube formation of Candida albicans. Dead yeast cells are uniformly stained red while viable yeast cells are unstained except for a red stained vacuole. This assay was used to demonstrate the difference in candidacidal activity between resident and in vivo stimulated peritoneal macrophages of CBA/J, BALB/c and CFW mice. Stimulation of peritoneal macrophages with Concanavalin A in vivo resulted in a significant increase in candidacidal activity in the macrophages from male and female mice. In addition, Concanavalin A-elicited macrophages from female BALB/c and CFW mice exhibited greater candidacidal activity than macrophages from male BALB/c and CFW mice whereas Concanavalin A-elicited macrophages from CBA/J male and female mice exhibited a similar candidacidal ability. Resident peritoneal macrophages from male mice were significantly less candidacidal than were macrophages from female mice with the exception of the macrophages from male CBA/J mice which were as active as the macrophages from female mice.

Animals↗
PubMed1987

Size distribution of airborne dust in Labrador iron mines.

The size distribution of the total airborne dust and its components approximates a straight line on a plot of log mass undersize against log aerodynamic size. The quartz component distribution has a reasonably constant slope, is close to the distributions found in other mines and mills, and follows the normal breakage laws. The results for the iron component suggest that the top size present is similar to that of quartz and that the slope is also similar. The slopes for total dust by weight are not as steep as for quartz and suggest a bimodal distribution consisting of a coarser mineral fraction mixed with a finer fraction from other sources, such as combustion products, that are often found. The slopes for manganese are sometimes much less than for iron or quartz and suggest that manganese is associated with a more crushable rock. The one finding of chromium suggests that it is associated mostly with very fine particles and, therefore, may have been dispersed as fume from an operation such as welding.

Air Pollutants, Occupational↗
PubMed1987

Intrinsic toe flexion deformity following correction of spastic equinovarus deformity in adults.

In the treatment of spastic equinovarus foot deformities in adults with neurologic impairment, various surgical procedures are used including the split anterior tibialis tendon transfer and tendo achilles lengthening. Release of the flexor hallucis longus and flexor digitorum longus tendons in the midfoot is routinely included with these procedures to correct or prevent toe curling. In follow-up, residual toe curling has been observed in some patients despite release of the long toe flexor tendons. This study was undertaken to investigate this problem and its consequences, treatment, and treatment success. Forty-one feet in 34 consecutive patients were examined for residual toe curling an average of 2.5 years postoperatively. Thirty-two feet (78%) were noted to have significant flexion deformities of the lesser toes. The residual toe curling caused pain in 72% of the feet and was associated with callosities on the dorsum of the toes in 59%. The incidence of residual toe curling secondary to spasticity of the flexor digitorum brevis and intrinsic muscles of the foot was similar in the patients who had sustained traumatic brain injury and in those who had suffered a cerebrovascular accident. Twelve of these feet (37%) underwent surgical release of the flexor digitorum brevis and intrinsic tendons to correct the toe curling. There were no complications of surgery and no recurrences of deformity following the surgery. A second surgical procedure to release the flexor digitorum brevis and intrinsic tendons to correct the toe curling was more commonly performed in the younger more active brain-injured patients than in the older stroke patients (44% versus 20%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Abnormal stimulated adherence of neonatal granulocytes: impaired induction of surface Mac-1 by chemotactic factors or secretagogues.

To identify possible secretory determinants of impaired hyperadherence and stimulated migration of neonatal granulocytes (NGs), we performed correlative studies of: (a) specific granule content and exocytosis, (b) secretago-gue-mediated upregulation of f-met-leu-phe (fMLP) receptors, (c) the chemotactic induction of the adhesive glycoproteins Mac-1 alpha (complement receptor 3) and beta, and (d) morphometric assessments of specific (peroxidase negative) granule depletion following chemotactic stimulation. Lactoferrin (LF) content of NG suspensions (cord blood or peripheral blood cells) was profoundly diminished (mean +/- SD 51% +/- 18% of normal) as compared with healthy adult granulocytes (AGs). Despite diminished cellular content, LF release by NG suspensions in response to fMLP was comparable to that of AGs. In contrast, LF release by NG suspensions was significantly diminished in response to phorbol myristate acetate (PMA) or calcium ionophor A23187 and/or during stimulated cell spreading, experimental conditions promoting overall greater LF depletion than chemotactic stimuli. In addition, NGs demonstrated an impaired capacity to upregulate fMLP receptors in response to PMA or A23187 when tested under the same experimental conditions. Baseline expression of the adhesive glycoproteins Mac-1 alpha and beta on NG surfaces was normal, but induction or upregulation of these proteins by chemotactic concentrations of fMLP, C5a as well as secretory (high) concentrations of PMA and A23187, was significantly diminished as compared with AGs. In contrast, chemotactic induction of the surface expression of the complement receptor-1 (CR-1) on NGs was normal. An impaired induction of Mac-1 alpha or beta was directly related to an impaired enhancement of adherence of NG in response to fMLP over a chemotactically relevant concentration range (10(-10) to 10(-7) mol/L). Moreover, in blocking-incubation experiments using anti-Mac-1 alpha/beta monoclonal antibodies (MAbs), significantly less inhibition of adherence by these MAbs was evident with fMLP-stimulated NG as compared with AG suspensions. Under selected chemotactic conditions, ultrastructural assessments of NGs demonstrated diminished peroxidase-negative granule loss in association with diminished granule-membrane fusion and the "addition" of plasma membrane. These studies suggest that abnormal expression of multiple surface determinants derived from peroxidase-negative granules or other intracellular pools may contribute to deficient chemotaxis or other inflammatory functions of NGs.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Surface↗
PubMed1987

The effects of soluble Saccharomyces cerevisiae mannan on the phagocytosis of Candida albicans by mouse peritoneal macrophages in vitro.

Saccharomyces cerevisiae mannan inhibited the phagocytic activity and phagocytic capacity of mouse peritoneal macrophages elicited by Concanavalin A (Con A) for Candida albicans yeast cells that were either unopsonized or opsonized with C3. The mannan had no effect on the phagocytosis of C. albicans opsonized with normal human serum or immunoglobulins. Phagolysosome fusion in macrophages was unimpaired by the presence of S. cerevisiae mannan, which supports previous observations that mannan does not interfere with neutrophil degranulation.

Animals↗
PubMed1987

Results of transfer of the flexor digitorum superficialis tendons to the flexor digitorum profundus tendons in adults with acquired spasticity of the hand.

Thirty-one patients who had transfer of the flexor digitorum superficialis tendons to the flexor digitorum profundus tendons en masse in thirty-four non-functional spastic hands were examined at an average of fifty months postoperatively. All of the patients had had a clenched-fist deformity preoperatively, with severe hygienic problems of the palmar skin and no active function of the hand. Postoperatively, all of the hands were in an open position, which allowed for good hygiene of the palmar surface. A minor wound infection developed in three patients. Neurectomy of the motor branch of the ulnar nerve distal to the Guyon canal was needed for control of spasticity of the intrinsic muscles in twenty-five hands. An intrinsic-minus deformity did not develop in any of the hands that had neurectomy of the ulnar nerve, although an intrinsic-plus deformity developed in seven of the nine hands that did not have a neurectomy.

Adult↗