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Biomedical subjects

K J Smith

Publications and source records attributed to K J Smith.

At least 91 records · Page 5Linked to original sources
PubMed1999

Micrococcus folliculitis in HIV-1 disease.

Organisms with little pathogenic potential in immunocompetent hosts may produce disease in HIV-1 + patients. We describe three HIV-1 + patients in late disease who presented with pruritic papules with central ulceration over the face and arms. In all the patients the eruptions had been present for months, and the patients did not develop sepsis. Biopsy specimens in all the patients showed large Gram-positive cocci, forming tetrads. Colony morphology, catalase positivity and coagulase negativity, and resistance to nitrofurantoin were used to separate micrococci from staphylococci. Micrococcus species are usually considered normal inhabitants of the skin; however, in patients with HIV-1 disease, Micrococcus species can produce localized cutaneous infections.

Adult↗
PubMed1999

Adjuvant therapy with hyaluronidase prior to excision of dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) are uncommon, low grade cutaneous malignancies, which rarely metastasize. Although surgery is the main therapy for these tumors, they commonly recur in spite of wide excisions. Hyaluronidase (HD) has been used both intralesionally as well as intravenously as an adjuvant in therapy of both epithelial and mesenchymal malignancies to decrease local spread, to potentiate differentiation induced apoptosis, and to potentiate the tissue penetration of chemotherapeutic agents. In addition, there is a long history of intralesional HD use without significant complications. The biologic characteristics of DFSP including the observation that hyaluronic acid is commonly present and sometimes is increased in these tumors and the known effects of HD therapy in other malignancies suggested to us that HD pretreatment may be a helpful adjuvant in the surgical management of DFSPs. Following diagnostic biopsy of a recurrent DFSP, the patient was treated for 4 weeks with intralesional HD injections. RESULTS: Based on margins necessary for complete excision from past studies, this patient had decreased margin width and thus had a postoperative wound size less than was expected. The patient has had no evidence of recurrence at 24 months follow-up.

Chemotherapy, Adjuvant↗
PubMed1999

Infiltrative glomus tumor arising from a benign glomus tumor: a distinctive immunohistochemical pattern in the infiltrative component.

Malignant glomus tumors (MGT) are rare. Although metastatic MGT has been reported, most MGT have only been locally aggressive, some with multiple local recurrences. We report an additional case of an infiltrative glomus tumor. In addition to the pattern of immunohistochemical staining for alpha-smooth muscle actin (SM-actin) previously described, we performed immunohistochemical stains for Ki-67 and CD34. The infiltrative component of the glomus tumor showed variably decreased staining with SM-actin and occasional tumor cells showed nuclear staining with Ki-67. CD34 staining occurred in stromal cells forming the pseudocapsule in the benign component of this tumor and in other benign glomus tumors. The infiltrative component showed increased CD34 stromal cells. Although Ki-67 staining showed only an occasional proliferative cell, the immunohistochemical staining pattern of CD34 and SM-actin raise the possibility that the infiltrative component of this tumor may have differences in the degree of differentiation from the circumscribed part and that local factors could support its spread from a conventional benign glomus tumor.

Actins↗
PubMed1999

Demyelination: the role of reactive oxygen and nitrogen species.

This review summarises the role that reactive oxygen and nitrogen species play in demyelination, such as that occurring in the inflammatory demyelinating disorders multiple sclerosis and Guillain-Barré syndrome. The concentrations of reactive oxygen and nitrogen species (e.g. superoxide, nitric oxide and peroxynitrite) can increase dramatically under conditions such as inflammation, and this can overwhelm the inherent antioxidant defences within lesions. Such oxidative and/or nitrative stress can damage the lipids, proteins and nucleic acids of cells and mitochondria, potentially causing cell death. Oligodendrocytes are more sensitive to oxidative and nitrative stress in vitro than are astrocytes and microglia, seemingly due to a diminished capacity for antioxidant defence, and the presence of raised risk factors, including a high iron content. Oxidative and nitrative stress might therefore result in vivo in selective oligodendrocyte death, and thereby demyelination. The reactive species may also damage the myelin sheath, promoting its attack by macrophages. Damage can occur directly by lipid peroxidation, and indirectly by the activation of proteases and phospholipase A2. Evidence for the existence of oxidative and nitrative stress within inflammatory demyelinating lesions includes the presence of both lipid and protein peroxides, and nitrotyrosine (a marker for peroxynitrite formation). The neurological deficit resulting from experimental autoimmune demyelinating disease has generally been reduced by trial therapies intended to diminish the concentration of reactive oxygen species. However, therapies aimed at diminishing reactive nitrogen species have had a more variable outcome, sometimes exacerbating disease.

Animals↗
PubMed1999

Kaposi's sarcoma in women: A clinicopathologic study.

BACKGROUND: Although all epidemiologic subsets of Kaposi's sarcoma (KS) (i.e., sporadic, endemic, epidemic, and iatrogenic) have an association with human herpes virus 8 (HHV8), these subsets occur in patient populations with distinctive clinical features. To a variable degree men outnumber women in all subsets. OBJECTIVE: A retrospective study of women with histologically proven cutaneous KS was undertaken to determine the clinical and histopathologic features, as well as any associations. METHODS: Two hundred and fifty cases of cutaneous KS in women from 1975 to 1993 were reviewed. RESULTS: Of the patients, 80% were more than 60 years of age, and of the patients less than 60 years old, 28 were from areas of the world with endemic KS. All HIV+ patients but one were from areas of endemic KS. Two patients were renal transplant patients. Sixty-four percent of the patients had single lesions and 21% recurrent lesions. Twelve patients had, or were known to develop, internal involvement, and in six patients the cause of death was KS. All but four cases histologically showed areas of solid proliferations of tumour cells consistent with plaque or tumour stage. An angiosarcoma-like histologic pattern appeared to be associated with more aggressive epidemiologic subsets. High mitotic rates were rarely seen and did not correlate with aggressive epidemiologic subsets. CONCLUSION: Kaposi's sarcoma in women is diagnosed almost exclusively in plaque or tumour stage. The majority of women within our study fit within the epidemiologic subset of sporadic KS.

Adult↗
PubMed1999

Immunohistochemical staining for Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, CD34, and factor XIIIa in nevus sebaceus.

Increased expression of p53 has been found in the majority of basal cell carcinomas (BCCs). The pattern and intensity of this staining, as well as staining for proliferation antigens, seems to correlate with behavior of histologic subtypes of BCC. Nevus sebaceus (NS) is considered a hamartoma. Multiple epithelial neoplasms do arise in NS, and, rarely, they show an aggressive biologic behavior. Significant numbers of these neoplasms, however, have areas of basaloid hyperplasia that are often reported as BCC. Although morphologically similar to BCC, the mechanism underlying the development of these areas has not been investigated, so we sought to evaluate the expression of Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, Factor XIIIa, and CD34 in areas showing basaloid hyperplasia, arising in NS. We performed immunohistochemical stains for Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, Factor XIIIa, and CD34 on seven cases of NS with areas of basaloid hyperplasia. All of the eight cases of NS showed diffuse positive membrane staining for Ber-EP4 and negative nuclear staining for p53. Proliferating cell nuclear antigen and Ki-67 staining was only slightly increased in the areas of basaloid hyperplasia, compared with the surrounding epidermis and with areas of the epidermis peripheral to the hamartomatous proliferation, and bcl-2 was only focally positive. Factor XIIIa-positive cells and CD34-positive vascular endothelial cells were increased within the subjacent dermis, a pattern suggestive of follicular differentiation. Our findings suggest that even though areas of basaloid hyperplasia in NS are morphologically similar to BCC, they are induced by different stimulatory and molecular mechanisms. These different mechanisms result in expression of immunohistochemical markers more characteristic of benign follicular tumors than of BCC.

Adolescent↗
PubMed1999

Glial heterotopia in the subcutaneous tissue overlying T-12.

Heterotopic glial nodules occur most commonly in the head and neck area, and are theorized to arise following abnormalities in the development of the facial and skull bone plates. However, in spite of the fact that some of these lesions are associated with communication with the central nervous system (CNS), the lack of a meningeal component, argues against simple herniation and separation of brain tissue through a defect in the skull. We present an infant with a nodule directly over the spine present in the T-12 region with no skin abnormalities. Magnetic resonance imaging (MRI) and computerized axial tomography (CT) showed no spinal abnormalities with an overlying fibrotic soft tissue mass. The patient had no other associated clinical findings. Histologic findings showed a cellular component arising within the reticular dermis with a deep circumscribed margin. The nodule contained irregularly shaped cells containing abundant cytoplasm and indistinct cellular margins with bland nuclei. These cells were clustered around and between a fibro-mucinous stroma. Immunohistochemical stains showed positive staining for S-100 protein, vimentin, GFAP, NSE, and CD57, and negative staining for Ki-67, CD34, Neurofilament protein, cytokeratin, and EMA. The spindle cells showed positive staining for CD34 and vimentin. The clinical and histologic features and immunohistochemical profiles are used to separate this lesion from the closely related, ependymal rests, ependymomas, and primary cutaneous chorodomas.

CD57 Antigens↗
PubMed1998

Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein.

Susceptibility to multiple sclerosis is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 (DRB1*1501) haplotype. The structure of HLA-DR2 was determined with a bound peptide from human myelin basic protein (MBP) that is immunodominant for human MBP-specific T cells. Residues of MBP peptide that are important for T cell receptor recognition are prominent, solvent exposed residues in the crystal structure. A distinguishing feature of the HLA-DR2 peptide binding site is a large, primarily hydrophobic P4 pocket that accommodates a phenylalanine of the MBP peptide. The necessary space for this aromatic side chain is created by an alanine at the polymorphic DRbeta 71 position. These features make the P4 pocket of HLA-DR2 distinct from DR molecules associated with other autoimmune diseases.

Binding Sites↗
PubMed1998

Crystal structures of HLA-A*0201 complexed with antigenic peptides with either the amino- or carboxyl-terminal group substituted by a methyl group.

The crystal structures of class I major histocompatibility complex (MHC) molecules complexed with antigenic peptides revealed a network of hydrogen bonds between the charged amino- and carboxyl-termini of the peptides and conserved MHC residues at both ends of the peptide binding site. These interactions were shown to contribute substantially to the stability of class I MHC/peptide complexes by thermal denaturation studies using synthetic peptides in which either the amino- or carboxyl-terminal group is substituted by a methyl group. Here we report crystal structures of HLA-A*0201 complexed with these terminally modified synthetic peptides showing that they adopt the same bound conformation as antigenic peptides. A number of variations in peptide conformation were observed for the terminally modified peptides, including in one case, a large conformational difference in four central peptide residues that is apparently caused by the lattice contact. This is reminiscent of the way binding a T-cell receptor changed the conformation of central residues of an MHC-bound peptide. The structures determined identify which conserved hydrogen bonds are eliminated in terminally substituted peptides and suggest an increased energetic importance of the interactions at the peptide termini for MHC-peptide stability.

Crystallography, X-Ray↗
PubMed1998

Expression and crystallization of the complex of HLA-DR2 (DRA, DRB1*1501) and an immunodominant peptide of human myelin basic protein.

HLA-DR2 is associated with susceptibility to multiple sclerosis (MS). A peptide from human myelin basic protein (MBP, residues 85-99) was previously found to bind to purified HLA-DR2 (DRA, DRB1*1501) and to be recognized by human MBP-specific T cell clones. Soluble HLA-DR2 was expressed in the baculovirus system by replacing the hydrophobic transmembrane regions and cytoplasmic segments of DRalpha and DRbeta with leucine zipper dimerization domains from the transcription factors Fos and Jun. In the expression construct, the MBP(85-99) sequence was covalently linked to the N terminus of the mature DRbeta chain. The recombinant protein was secreted by Sf9 cells infected with the recombinant baculovirus and purified by affinity chromatography. The leucine zipper dimerization domains were then cleaved from the assembled HLA-DR2/MBP peptide complex with V8 protease, and the protein was further purified by anion-exchange HPLC. Analysis by HPLC gel filtration indicated that the HLA-DR2/MBP peptide complex did not have a tendency to aggregate. The purified HLA-DR2/MBP peptide complex readily crystallized by the hanging drop method in 15-18% polyethylene glycol 6000/100 mM glycine, pH 3.5. At a synchrotron radiation source, a crystal with a tetragonal space group diffracted to a resolution of 2.6 A. The expression of such homogenous HLA-DR/peptide complexes may facilitate cocrystallization with T cell receptors as well as other molecules involved in T cell receptor recognition and signaling.

Amino Acid Sequence↗
PubMed1998

Sensitivity of cross-reacting antihuman antibodies in formalin-fixed porcine skin: including antibodies to proliferation antigens and cytokeratins with specificity in the skin.

Although no animal is a perfect skin model for the study of toxicological and therapeutic agents, structurally the pig may be superior to even non-human primates. Because our work involves effects of toxicological and therapeutic agents on the skin, we wanted to identify stains which may prove useful as well as determine cross-reactivity of some newer antihuman antibodies. We performed a battery of formalin-fixed skin from weanling pigs and minipigs. The battery of antibodies included LCA, CD3, OPD-4, CD34, UCHL-1, L-26, KP-1, MAC-387, Factor XIIIa, Leu-7, S-100 protein, HMB-45, GFAP, synaptophysin, neurofilament protein, ubiquitin, vimentin, type IV collagen, laminin, fibronectin, Factor VIII related antigen, Desmin-M, smooth muscle actin, cytokeratin 7, cytokeratin 20, AEI/AE3, CAM 5.2, EMA, GCDFP, Ki-67, and PCNA. Immunohistochemical stains for CD3, Leu-7, S-100 protein, type IV collagen, laminin, Factor VIII related antigen, GFAP, synaptophysin, neurofilament protein, ubiquitin, smooth muscle actin, vimentin, Desmin-M, cytokeratin 7, cytokeratin 20, AE1/AE3, CAM 5.2, Ki-67 and PCNA showed consistent cross-reactivity. In formalin-fixed tissue, only antibodies to lymphoreticular cells showed poor cross-reactivity. A high percentage of the remaining antibodies did show good cross-reactivity but with some interesting similarities and differences in specificity.

Animals↗
PubMed1998

Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/Tax peptide complex using different TCR amino acids.

The three-dimensional structure of a human alphabeta T cell receptor (TCR), B7, bound to the HLA-A2 molecule/HTLV-1 Tax peptide complex was determined by x-ray crystallography. Although different from the A6 TCR, previously studied, in 16 of the 17 residues that contact HLA-A2/Tax, the B7 TCR binds in a similar diagonal manner, only slightly tipped and rotated, relative to the A6 TCR. The structure explains data from functional assays on the specificity differences between the B7 and A6 TCRs for agonist, partial agonist, and null peptides. The existence of a structurally similar diagonal binding mode for TCRs favors mechanisms based on the formation of geometrically defined supramolecular assemblies for initiating signaling.

Amino Acid Sequence↗