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Biomedical subjects

S B Woo

Publications and source records attributed to S B Woo.

At least 19 recordsLinked to original sources
PubMed2001

The binding of zinc and copper ions to nerve growth factor is differentially affected by pH: implications for cerebral acidosis.

It has recently been shown that transition metal cations Zn2+ and Cu2+ bind to histidine residues of nerve growth factor (NGF) and other neurotrophins (a family of proteins important for neuronal survival) leading to their inactivation. Experimental data and theoretical considerations indicate that transition metal cations may destabilize the ionic form of histidine residues within proteins, thereby decreasing their pK(a) values. Because the release of transition metal cations and acidification of the local environment represent important events associated with brain injury, the ability of Zn2+ and Cu2+ to bind to neurotrophins in acidic conditions may alter neuronal death following stroke or as a result of traumatic injury. To test the hypothesis that metal ion binding to neurotrophins is influenced by pH, the effects of Zn2+ and Cu2+ on NGF conformation, receptor binding and NGF tyrosine kinase (trkA) receptor signal transduction were examined under conditions mimicking cerebral acidosis (pH range 5.5-7.4). The inhibitory effect of Zn2+ on biological activities of NGF is lost under acidic conditions. Conversely, the binding of Cu2+ to NGF is relatively independent of pH changes within the studied range. These data demonstrate that Cu2+ has greater binding affinity to NGF than Zn2+ at reduced pH, consistent with the higher affinity of Cu2+ for histidine residues. These findings suggest that cerebral acidosis associated with stroke or traumatic brain injury could neutralize the Zn2+-mediated inactivation of NGF, whereas corresponding pH changes would have little or no influence on the inhibitory effects of Cu2+. The importance of His84 of NGF for transition metal cation binding is demonstrated, confirming the involvement of this residue in metal ion coordination.

Acidosis↗
PubMed2000

Salivary gland changes in chronic fatigue syndrome: a case-controlled preliminary histologic study.

OBJECTIVE: The purpose of this preliminary study is to compare labial salivary gland changes of 11 patients with chronic fatigue syndrome with control subjects. STUDY DESIGN: Changes in labial salivary glands were graded from 0 to 3+ for acinar dilatation, ductal dilatation, periductal fibrosis, plasmacytic infiltrate, lymphocytic infiltrate, mast cell infiltrate, and lymphocytic aggregates or foci. RESULTS: Four of the 11 subjects had 2+ to 3+ changes in at least 4 of the 7 parameters examined. Only the presence of mast cells was statistically significant between the 2 groups. Two of these 4 patients had 1 lymphocytic focus per 4 mm(2) of tissue. CONCLUSIONS: The salivary gland changes in patients with chronic fatigue syndrome show varying degrees of ductal and acinar dilatation, periductal fibrosis, lymphoplasmacytic infiltrates, and occasional lymphocytic foci, all suggestive of primary gland damage. The one parameter that showed statistical significance was the presence of mast cells (Fisher exact test, 0.0125).

Adult↗
PubMed1998

A TrkA-selective, fast internalizing nerve growth factor-antibody complex induces trophic but not neuritogenic signals.

Nerve growth factor (NGF) is a neurotrophin that induces neuritogenic and trophic signals by binding to TrkA and/or p75 receptors. We report a comparative study of the binding, internalization, and biological activity of NGF versus that of NGF in association with an anti-NGF monoclonal antibody (mAb NGF30), directed against the C termini of NGF. NGF.mAb complexes do not bind p75 effectively but bind TrkA with high affinity. After binding, NGF. mAb complexes stimulate internalization faster and to a larger degree than NGF. NGF.mAb-induced activation of TrkA, Shc, and MAPK is transient compared with NGF-induced activation; yet NGF and NGF. mAb afford identical trophic responses. In contrast, NGF induces Suc-1-associated neurotrophic activating protein phosphorylation and neuritogenic differentiation, but NGF.mAb does not. Thus, an absolute separation of trophic and neuritogenic function is seen for NGF.mAb, suggesting that biological response modifiers of neurotrophins can afford ligands with selected activities.

Antibodies, Monoclonal↗
PubMed1998

Characterization of the recombinant extracellular domain of the neurotrophin receptor TrkA and its interaction with nerve growth factor (NGF).

Nerve growth factor (NGF) is the prototype of a family of neurotrophins that support important neuronal programs such as differentiation and survival of a subset of sympathetic, sensory, and brain neurons. NGF binds to two classes of cell surface receptors: p75LANR and p140TrkA. NGF binding to p140TrkA initiates the neuronal signaling pathway through activation of the tyrosine kinase activity, which subsequently results in a rapid signal transduction through a phosphorylation cascade. To examine this crucial signaling step in more detail, the TrkA extracellular domain polypeptide (TrkA-RED) was overexpressed in Sf21 insect cells and purified to homogeneity. The recombinant TrkA-RED is a 70 kDa acidic glycoprotein with a pI of 5.1, and mimics the intact TrkA receptor for NGF binding with a dissociation constant, Kd, of 2.9 nM. Thus, the recombinant TrkA-RED is functionally competent and can be used to elucidate the interaction of NGF and TrkA receptor. Circular dichroism difference spectra indicated that, upon association of NGF with TrkA-RED, a minor conformational change occurred to form a complex with decreased ordered secondary structure. Interaction between NGF and TrkA-RED was also demonstrated by size exclusion chromatography, light scattering, and chemical crosslinking with evidence for formation of a higher molecular weight complex consistent with a (TrkA-RED)2-(NGF dimer) complex. Association and dissociation rates of 5.6 x 10(5) M(-1) s(-1) and 1.6 x 10(-3) s(-1), respectively, were determined by biosensor technology. Thus, initiation of signaling may stem from NGF-induced receptor dimerization concomitant with a small conformational change.

Animals↗
PubMed1997

Oral recrudescent herpes simplex virus infection.

OBJECTIVE: The objective of this study is to determine the frequency of involvement of different intraoral sites by oral recrudescent herpes simplex virus in immunocompromised patients and whether keratinized intraoral sites are always affected by this virus. STUDY DESIGN: The records of 30 hospitalized patients who had oral ulcers culture positive for herpes simplex virus were reviewed for the location of oral ulcers, febrile episodes, and medical diagnoses. RESULTS: The data revealed that oral recrudescent herpes simplex virus may involve any intraoral site in immunocompromised patients with nonkeratinized sites representing approximately half of all sites; this is more frequent than has been previously reported. Twenty-six (86.7%) of 30 patients had no evidence of herpes labialis, and 13 (43.3%) of 30 patients were afebrile. CONCLUSION: It is recommended that all oral ulcers, in immunocompromised patients should be cultured for herpes simplex virus regardless of their location. Early diagnosis reduces patient morbidity because effective treatment in the form of acyclovir is readily available.

Adult↗
PubMed1997

Graft-vs.-host disease.

Bone marrow transplantation (BMT) is the treatment of choice for many leukemias, lymphomas, bone marrow failure syndromes, and immunodeficiency disorders, and is the primary and salvage therapy for many solid malignancies. With the establishment of national and international marrow banks, unrelated allogeneic BMT is being performed with increasing frequency. Graft-vs.-host disease (GVHD) remains a major complication of allogeneic BMT, occurring in 25% to 70% of patients despite GVHD prophylaxis, with the skin, gastro-intestinal tract, and liver as primary target organs. Oral findings are seen in both acute and chronic GVHD. In acute GVHD, the oral lesions are often painful, erythematous, ulcerative, and desquamative. In chronic GVHD, they are lichenoid with associated erythema and ulcerations; additionally, they may be associated with a sicca syndrome characterized by xerostomia and progressive salivary gland atrophy. General principles of BMT are discussed, as are systemic and local therapeutic options for oral GVHD.

Acute Disease↗
PubMed1997

Off-site dental evaluation program for prospective bone marrow transplant recipients.

The authors evaluated the usefulness of an off-site dental evaluation program for bone marrow recipients. This evaluation packet enabled patients scheduled for bone marrow transplants to be evaluated by, and receive any treatment from, their own dentist rather than a dentist at the transplant center. The program generally was effective in achieving its goals and was well-accepted by patients and dentists alike.

Adolescent↗
PubMed1996

Characterization of histidine residues essential for receptor binding and activity of nerve growth factor.

The role of the four histidine residues in receptor binding and activity of mouse nerve growth factor (NGF) was investigated using both site-directed mutagenesis and chemical modification with diethyl pyrocarbonate. Replacement of His-75 or His-84 with alanine resulted in decreased biological activity and decreased affinity for p140(trkA); however, with H75A only, a 5-fold increased affinity toward p75(LANR) was observed. The effect of simultaneous replacement of both His-75 and His-84 was neither additive nor synergistic. Slight perturbations in circular dichroism spectra and weakened self-association of the mutants indicated that His-75 and His-84 may be involved in stability, dimerization, and/or folding of NGF. Diethyl pyrocarbonate modification of His-4 and His-8 in the H75A/H84Q double mutant abolished neuritogenesis, binding to both receptors, and phosphorylation of p140(trkA) in PC12 cells. These chemical and mutational results confirm and clarify previous evidence for the involvement of His-75 and His-84 (Dunbar, J. C., Tregear, G. W., and Bradshaw, R. A. (1984) J. Protein Chem. 3, 349-356) or His-4 and His-8 (Shih, A., Laramee, G. R., Schmelzer, C. H., Burton, L. E., and Winslow, J. W. (1994) J. Biol. Chem. 269, 27679-27686) in receptor binding of NGF. At least three and possibly all four histidines, which are located in three spatially distinct regions, contribute to maintenance of functional sites that are essential for receptor binding and activity of NGF.

Amino Acid Sequence↗
PubMed1996

Recurrent aphthous ulcers: a review of diagnosis and treatment.

Recurrent aphthous ulcers, or RAU--also called canker sores--are among the oral mucosal conditions that dentists and physicians see most commonly in their patients. Several systemic conditions are associated with oral aphthouslike ulcers, and aphthae themselves often are mistaken for recrudescent oral herpes simplex virus, or HSV, infections. This article will review RAU, describe systemic conditions associated with aphthous-like ulcerations and discuss the differences between RAU and recrudescent oral HSV infections.

Anti-Bacterial Agents↗
PubMed1995

Alteration of NH2-terminal residues of nerve growth factor affects activity and Trk binding without affecting stability or conformation.

The role of the NH2-terminal region of nerve growth factor (NGF) was studied with an NGF delta 9/13 deletion mutant, overexpressed in a baculovirus system, and mouse NGF truncated at Met-9 by cleavage with CNBr (des-(1-9)-NGF). Structural studies have been performed on the purified proteins, in addition to biological activity assessment, in order to determine effects of such modifications on global conformation and stability. The activity of NGF delta 9/13 was reduced below detectable levels, and the activity of the des-(1-9)-NGF form was decreased by at least a 50-fold in a PC12 bioassay. Competitive binding of NGF delta 9/13 to low affinity receptors on PC12 cells was not impaired; however, the mutant was not capable of competing for the cold chase-stable, high affinity binding of NGF to the cells. The binding of NGF delta 9/13 to Sf21 cells ectopically expressing the TrkA NGF receptor was also abolished. Thus, deletion of residues 9-13 significantly altered the binding affinity for the high affinity receptors on PC12 cells and for the TrkA receptor, but not for the low affinity receptor. Neither the secondary structure, determined by circular dichroism, nor the conformational stability determined by equilibrium denaturation of NGF delta 9/13 was altered as compared with wild type NGF. Slight conformational and stability perturbations of des-(1-9)-NGF were revealed by the same analysis; however, these changes were found to reflect the influence of the formic acid treatment, not the truncation of 9 residues. Our results support the conclusion that the NH2-terminal domain encompassing residues 1-9 and 9-13 is essential for maintaining the binding capability of NGF for high affinity TrkA receptors. Moreover, conformational and stability data show that the functional results of these modifications of the NH2-terminal region are directly due to receptor binding and not to secondary effects of improper folding or other indirect structural changes.

Animals↗
PubMed1993

A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients.

BACKGROUND: Few longitudinal studies have investigated the onset, duration, and resolution of ulcerative mucositis in bone marrow transplant recipients. This study prospectively followed a group of such patients on a daily basis to obtain data on the incidence of ulcerative mucositis, location and duration of lesions, severity with different conditioning regimens, and the relationship of such mucositis to the absolute neutrophil count. METHODS: Fifty-nine bone marrow transplant recipients on prophylactic acyclovir were examined daily for 26 days after marrow infusion, and all oral ulcerative lesions were recorded. RESULTS: Oral ulcers occurred in 76.3% of patients, began at a mean of 5 days after marrow infusion (day + 5), and lasted for a median of 6 days. More than 90% of patients showed complete resolution of ulcers on or before day + 15, and all showed resolution when the absolute neutrophil count was > 500 cells/ml. Persistence of ulcers was noticed in patients who had oral graft-versus-host disease and in some patients who initially developed more severe ulcerations. Ninety-six percent of ulcers were located on nonkeratinized mucosa. CONCLUSIONS: Ulcerative mucositis occurs in about 75% of bone marrow transplant recipients in the absence of herpes simplex virus infection. Most lesions occur on nonkeratinized mucosae which are vulnerable to trauma, especially if such mucosae are rendered atrophic by conditioning regimens. Oral ulcers may persist beyond day + 15 and after recovery of the neutrophil count in patients who initially develop more severe ulcerations or in patients who develop graft-versus-host disease.

Acyclovir↗
PubMed1993

Effect of deletion from the carboxyl terminus of the 12 S subunit on activity of transcarboxylase.

Transcarboxylase from Propionibacterium shermanii is a biotin-containing enzyme which catalyzes the reversible transfer of a carboxyl group from methylmalonyl-CoA to pyruvate. The central hexameric 12 S subunit of the enzyme associates with six 6 S subunits in the complete enzyme complex. We have constructed a series of cloned genes which encode COOH-terminal truncations of the 12 S subunit. Five of these subunits, which remained soluble following expression in Escherichia coli and were missing from 39 to 97 COOH-terminal amino acids, were purified and compared to the full-length subunit after enzyme complexes were assembled in vitro. All of the truncated subunits were 90% as active in the transcarboxylase reaction as wild type except the reaction containing the shortest complex, TC-12 S (1-507), which had 54% of the wild type activity (TC-12 S-WT). The reduced activity was not due to a lack of CoA ester binding sites or the Km for substrate. However, TC-12 S (1-507) was slower to form than TC-12 S-WT and had more incomplete complexes as judged by high performance liquid chromatography gel filtration profiles and electron microscopy. Isolated TC-12 S (1-507) was 70-80% as active as TC-12 S-WT. We also noted that the truncated form was heat-labile compared to wild type. We conclude that the COOH-terminal region of the 12 S subunit plays a role in assembly and stability of the hexamer and also affects the binding of 6 S subunits to form enzyme complexes. Once complexes do form, the catalytic capacity of TC-12 S (1-507) is almost the same as TC-12 S-WT.

Acyl Coenzyme A↗
PubMed1993

Assessment of the need for treatment of postendodontic asymptomatic periapical radiolucencies in bone marrow transplant recipients.

Oral screening and treatment of existing oral disease before bone marrow transplantation have been reported to decrease the incidence of infectious complications during bone marrow transplantation. Information about the adverse sequelae of specific preexisting oral diseases during bone marrow transplantation is lacking. The presence of postendodontic periapical radiolucencies may suggest recurrent or latent infection. The purpose of this study was to compare the effect of endodontic treatment with nontreatment of asymptomatic postendodontic periapical radiolucencies on the frequency of infectious oral complications during bone marrow transplantation. The records of 276 patients undergoing bone marrow transplantation examined between July 1988 and June 1991 were reviewed retrospectively. Twenty-three postendodontic periapical radiolucencies were identified in 8 women and 15 men. The mean age of patients was 41 years (range, 25 to 58 years). Fourteen of the lesions were untreated, and nine were treated before bone marrow transplantation. When outcomes of transplant complications were compared, neither increased systemic infection as measured by neutropenic days febrile nor local oral infectious complications were significantly different. These results suggest that nontreatment of asymptomatic postendodontic periapical radiolucencies does not increase the incidence of infectious complications during bone marrow transplantation.

Adult↗
PubMed1993

Primary structure of the monomer of the 12S subunit of transcarboxylase as deduced from DNA and characterization of the product expressed in Escherichia coli.

Transcarboxylase from Propionibacterium shermanii is a complex biotin-containing enzyme composed of 30 polypeptides of three different types: a hexameric central 12S subunit to which 6 outer 5S subunits are attached through 12 1.3S biotinyl subunits. The enzyme catalyzes a two-step reaction in which methylmalonyl coenzyme A and pyruvate serve as substrates to form propionyl coenzyme A (propionyl-CoA) and oxalacetate, the 12S subunit specifically catalyzing one of the two reactions. We report here the cloning, sequencing, and expression of the 12S subunit. The gene was identified by matching amino acid sequences derived from isolated authentic 12S peptides with the deduced sequence of an open reading frame present in a cloned P. shermanii genomic fragment known to contain the gene encoding the 1.3S biotinyl subunit. The cloned 12S gene encodes a protein of 604 amino acids and of M(r) 65,545. The deduced sequence shows regions of extensive homology with the beta subunit of mammalian propionyl-CoA carboxylase as well as regions of homology with acetyl-CoA carboxylase from several species. Two genomic fragments were subcloned into pUC19 in an orientation such that the 12S open reading frame could be expressed from the lac promoter of the vector. Crude extracts prepared from these cells contained an immunoreactive band on Western blots (immunoblots) which comigrated with authentic 12S. The Escherichia coli-expressed 12S was purified to apparent homogeneity by a three-step procedure and compared with authentic 12S from P. shermanii. Their quaternary structures were identical by electron microscopy, and the E. coli 12S preparation was fully active in the reactions catalyzed by this subunit. We conclude that we have cloned, sequenced, and expressed the 12S subunit which exists in a hexameric active form in E.coli.

Amino Acid Sequence↗
PubMed1990

The role of herpes simplex virus in the development of oral mucositis in bone marrow transplant recipients.

Herpes simplex virus (HSV) has been implicated as a major etiologic factor in the development of ulcerative mucositis in bone marrow transplant (BMT) recipients. In this study, 60 patients who received BMTs were evaluated for at least 30 days post-transplant for ulcerative mucositis and the presence of culturable HSV. Fifty-nine patients received prophylactic acyclovir. Forty-six patients developed ulcerative lesions and 45 of these were culture negative for HSV. Neither the source of transplant (autologous versus allogenic) nor the HSV antibody status of the patient affected the frequency of mucositis. The conditioning regimen appeared to be the most significant factor contributing to the severity of ulcerative mucositis. While the majority of ulcers occurred on movable nonkeratinized mucosa in BMT recipients, the usual sites of reactivation of intraoral HSV are nonmovable, keratinized mucosa. We conclude that HSV is probably not a major etiologic agent of mucositis in BMT recipients and that acyclovir is an effective agent in preventing HSV reactivation.

Acyclovir↗
PubMed1989

Effects of acetylene on hydrogenases from the sulfate reducing and methanogenic bacteria.

The effect of acetylene on the activity of the three types of hydrogenase from the anaerobic sulfate reducing bacteria has been investigated. The (Fe) hydrogenase is resistant to inhibition by acetylene while the nickel-containing hydrogenases are inhibited by acetylene with the (NiFe) hydrogenase being 10-50 fold more sensitive than the (NiFeSe) hydrogenase. In addition the Ni(III) EPR signal (g approximately 2.3) of the "as isolated" (NiFe) hydrogenase was significantly decreased in intensity upon exposure to acetylene.

Acetylene↗