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S P Smith

Publications and source records attributed to S P Smith.

At least 19 recordsLinked to original sources
PubMed1998

A novel calcium-sensitive switch revealed by the structure of human S100B in the calcium-bound form.

BACKGROUND: S100B is a homodimeric member of the EF-hand calcium-binding protein superfamily. The protein has been implicated in cellular processes such as cell differentiation and growth, plays a role in cytoskeletal structure and function, and may have a role in neuropathological diseases, such as Alzheimers. The effects of S100B are mediated via its interaction with target proteins. While several studies have suggested that this interaction is propagated through a calcium-induced conformational change, leading to the exposure of a hydrophobic region of S100B, the molecular details behind this structural alteration remain unclear. RESULTS: The solution structure of calcium-saturated human S100B (Ca(2+)-S100B) has been determined by heteronuclear NMR spectroscopy. Ca(2+)-S100B forms a well defined globular structure comprising four EF-hand calcium-binding sites and an extensive hydrophobic dimer interface. A comparison of Ca(2+)-S100B with apo S100B and Ca(2+)-calbindin D9k indicates that while calcium-binding to S100B results in little change in the site I EF-hand, it induces a backbone reorientation of the N terminus of the site II EF-hand. This reorientation leads to a dramatic change in the position of helix III relative to the other helices. CONCLUSIONS: The calcium-induced reorientation of calcium-binding site II results in the increased exposure of several hydrophobic residues in helix IV and the linker region. While following the general mechanism of calcium modulatory proteins, whereby a hydrophobic target site is exposed, the 'calcium switch' observed in S100B appears to be unique from that of other EF-hand proteins and may provide insights into target specificity among calcium modulatory proteins.

Amino Acids↗
PubMed1998

Maxillary removal and reinsertion for anterior cranial base tumors: long-term results.

OBJECTIVE: To evaluate complications and sequelae of maxillary removal and reinsertion for anterior cranial base tumors. DESIGN: A retrospective review of patients who underwent maxillary removal and reinsertion from 1990 to 1996. SETTING: The Arthur G. James Cancer Hospital and Research Institute at The Ohio State University, Columbus. PATIENTS: A consecutive sample of 46 patients who underwent maxillary removal and reinsertion. The patients ranged in age from 11 to 77 years and were followed up for as long as 6 years after surgery. There were 16 benign and 30 malignant lesions. MAIN OUTCOME MEASURES: Intraoperative, postoperative (1-10 days), short-term (11 days through 3 months), and long-term (>3 months) complications; survival status of patients; and adjuvant therapy. RESULTS: Four patients (9%) had undergone previous radiotherapy; 9 (20%) received intraoperative radiation therapy; and 23 (50%) received planned postoperative radiotherapy. No intraoperative complications were noted. The most common short-term complication found was transient diplopia, affecting 9 patients (20%). Diplopia resolved within 3 months in all but 2 patients, in whom the condition was permanent. There were 4 patients (9%) who required removal of the nasal dorsum plate, and 4 (9%) who required removal of maxillary plates that were exposed intranasally. Midface asymmetry as reported by the patient or noted on the physical examination was documented in only 2 patients. The most common long-term complication was nasal asymmetry, affecting 13 patients (28%). CONCLUSIONS: Maxillary removal allows improved visualization and access to anterior skull base lesions, while reinsertion of the maxillary fragment provides functional preservation and excellent cosmesis with few short- or long-term complications, even when adjuvant radiotherapy is used.

Adolescent↗
PubMed1998

A change-in-hand mechanism for S100 signalling.

S100 proteins are a group of small dimeric calcium-binding proteins making up a large subclass of the EF-hand family of calcium-binding proteins. Members of this family of proteins have been proposed to act as intracellular calcium modulatory proteins in a fashion analogous to that of the EF-hand sensor proteins troponin-C and calmodulin. Recently, NMR spectroscopy has provided the three-dimensional structures of the S100 family members S100A6 and S100B in both the apo- and calcium-bound forms. These structures have allowed for the identification of a novel calcium-induced conformational change termed the change-in-hand mechanism. Helix III of the C-terminal calcium-binding loop changes its helix-helix interactions (or handness) with the remainder of the molecule primarily owing to the reorientation of the backbone in an effort to coordinate the calcium ion. This reorientation of helix III exposes several residues in the C-terminus and linker regions of S100B resulting in the formation of a hydrophobic patch surrounded be a number of acidic residues. This site is the proposed region for protein-protein recognition.

Allosteric Regulation↗
PubMed1997

Identification and structural influence of a differentially modified N-terminal methionine in human S100b.

The calcium-binding protein S100b is a homodimer comprised of two identical 91-residue beta-subunits. Recombinant S100b is a heterogeneous protein, although the basis of this heterogeneity has not been established. We have used mass spectrometry and NMR spectroscopy to determine that heterogeneity in S100b arises from a mixture of formyl-S100b and desformyl-S100b when expressed in Escherichia coli. Reversed-phase HPLC purification of these two forms of S100b has allowed the differences in N-terminal composition to be used as a probe for tertiary contacts in the protein. The presence or absence of the N-terminal formyl group affected the chemical shifts of sequence neighboring residues and those in the linker of the protein (residues 40-43), indicating that these two regions are close in space.

Amino Acid Sequence↗
PubMed1997

Assignment and secondary structure of calcium-bound human S100B.

The NMR assignments of backbone 1H, 13C, and 15N resonances for calcium-bound human S100B were completed via heteronuclear multidimensional NMR spectroscopic techniques. NOE correlations, amide exchange, 3JHNH alpha coupling constants, and CSI analysis were used to identify the secondary structure for Ca-S100B. The protein is comprised of four helices (helix I, Glu2-Arg20; helix II, Glu31-Asn38; helix III, Gln50-Thr59; helix IV, Phe70-Phe87), three loops (loop I, Glu21-His25; loop II, Glu39-Glu49; loop III, Leu60-Gly66), and two beta-strands (strand I, Lys26-Lys28; strand II, Glu67-Asp69) which form a short antiparallel beta-sheet. Helix IV is extended by approximately one turn when compared to the secondary structures of apo-rat [Drohat et al. (1996) Biochemistry, 35, 11577-11588] and bovine S100B [Kilby et al. (1996) Structure, 4, 1041-1052]. In addition, several residues outside the calcium-binding loops in S100B undergo significant backbone chemical shift changes upon binding calcium which are not observed in the related protein calbindin D9k. Together these observations support previous site-directed mutagenesis, absorption spectroscopy, and cysteine chemical reactivity experiments, suggesting that the C-terminus in Ca-S100B is important for interactions with other proteins.

Amides↗
PubMed1996

Structural influence of cation binding to recombinant human brain S100b: evidence for calcium-induced exposure of a hydrophobic surface.

The dimeric calcium-binding protein S100b is proposed to undergo a calcium-induced structural change allowing it to interact, via a hydrophobic surface, with other proteins. Previously it has been suggested that calcium binding to S100b leads to the exposure of at least one phenylalanine residue (Mani et al., 1982, 1983). This effect appears to be "reversed" at higher ionic strength, leading to a possible reburying of phenylalanine residues (Mani et al., 1982, 1983). To study these effects, we monitored calcium binding to recombinant human S100b by NMR spectroscopy under different salt (KCI) conditions. 15N-Labeled glycine residues in S100b showed calcium-induced chemical shift changes similar to those reported for the related monomeric protein calbindin D9k, suggesting similar conformational changes are occurring in the calcium-binding loops of these two proteins. Calcium binding to S100b also resulted in a shifting and broadening of several 1H resonances from the Ca-S100b form only including those from the side chains of residues F14, F70, and F73 but not those of residue Y17. This broadening was enhanced with increased ionic strength (KCI). However, small additions ( < 15% v/v) of the hydrophobic solvent trifluoroethanol relieved this phenomenon, leading to narrower line widths. These observations are consistent with the calcium-induced exposure of at least one of these hydrophobic residues, resulting in self-association of the S100b dimer. Trifluoroethanol serves to dissociate these complexes back to the dimeric calcium species. We propose that this cluster of hydrophobic residues which include F14, F73, and F88 may be important for interactions with a target protein.

Base Sequence↗
PubMed1996

North American blastomycosis: the importance of a differential diagnosis.

Diseases from the major pathophysiological subgroups, including inflammatory, infectious, neoplastic, autoimmune, and metabolic disorders, can present in a very similar clinical manner. The importance of generating a broad differential diagnosis is supported by a case in which an 80-year-old white man presented with a verrucous plaque on the tip of his nose. The appropriate differential diagnosis for such a lesion as well as an overview of the disease diagnosed, North American blastomycosis, is presented.

Aged↗
PubMed1996

Charcot-Marie-Tooth disease type 1A: a family study with microsatellites.

Charcot-Marie-Tooth (CMT) disease (also called Hereditary Motor and Sensory Neuropathy) is an inherited peripheral neuropathy with a prevalence rate of 1 in 2,500. Charcot-Marie-Tooth disease type 1A (CMT1A), the most common autosomal dominant form of the disease, is associated with a duplication of a segment of chromosome 17 (17p11.2). In this report we present a three-generation family with CMT1A where simple sequence repeats (di- or tri-nucleotide repeats, also called microsatellites) were used in conjunction with polymerase chain reaction (PCR) to identify the duplication. The presence of three alleles or the presence of two alleles with a dosage ratio of 1:2 for the markers D17S839 and D17S921 indicates the presence of the duplicated segment in affected family members, whereas two alleles with a ratio of 1:1 indicate absence of the duplication. Several markers outside the duplication region which have two alleles with a dosage ratio of 1:1 were used as controls. Seven CMT1A patients in this family carry the CMT1A duplication. One 12-year-old boy who has not exhibited any clinical symptoms does not have the CMT1A duplication. We believe that this is a simple, rapid, and effective method to identify the CMT1A duplication in most patients suspected of having CMT1A.

Adult↗
PubMed1996

Dating-partner preferences among a group of inner-city African-American high school students.

The present study examines a set of characteristics that students may (or may not) value in a dating partner. A total of 80 inner-city high school students indicated how important they perceived certain qualities to be in a person they would like to date. Respondents were instructed to check the most appropriate category (very important, somewhat important, or not important) beside a list of 12 phrases. In order to determine meaningful patterns, a rank-ordering of mean values and a rarely used multidimensional scaling model were employed to further understand this widely researched aspect of dating. The rank-ordering indicates relationships between the students and attributes, while the scaling model reflects patterns between the rated attributes only. The results are in contrast to the previous literature regarding dating-partner preferences among African-American high school students.

Adolescent↗
PubMed1995

United we stand.

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Health Care Reform↗
PubMed1994

Acquired subglottic cysts in infancy.

OBJECTIVE: To evaluate the presentation and treatment of infants with acquired subglottic cysts. DESIGN: Case series seen over 12 years. SETTING: Academic tertiary referral pediatric medical center. PATIENTS: Eleven patients had subglottic cysts diagnosed. INTERVENTION: Four patients were treated with rupture with the tip of the endoscope. Seven patients underwent endoscopic marsupialization by means of carbon dioxide laser (n = 5) and by cup forceps (n = 2). OUTCOME MEASURES: Intraoperative cyst control. Symptomatic cyst recurrence. RESULTS: Initial cyst management was successful in all cases. There was one symptomatic recurrence in a patient who was managed with cyst rupture. There were no symptomatic recurrences in the group treated by marsupialization. The mean follow-up period was 6 years. CONCLUSIONS: Subglottic cysts should be considered in the ex-premature infant with a history of neonatal intubation who presents with stridor or respiratory difficulty. These ductal retention cysts can develop after periods of intubation of less than 24 hours. Endoscopic marsupialization is the recommended form of treatment.

Child, Preschool↗
PubMed1994

Psychological correlates of psychogenic seizures.

Psychological correlates of psychogenic seizures were studied. The MMPI, Portland Digit Recognition Test (PDRT; a forced choice measure of motivation), disability status, Face-Hand Test, and Finger Agnosia were compared in 53 patients with medically intractable seizure disorders who underwent intensive EEG monitoring. Using conventional neurologic criteria, 64% had diagnoses of epileptic seizures (ES) and 36% had psychogenic seizures (PS). PS patients were significantly higher in number of somatoform MMPI profiles and likelihood of applying for financial benefits, and significantly lower on the PDRT. PS patients made more Finger Agnosia errors. Differences on the Face-Hand Test were of borderline significance. The results support the existence of multiple psychometric correlates of PS.

Adult↗