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Biomedical subjects

E Wong

Publications and source records attributed to E Wong.

At least 163 records · Page 9Linked to original sources

Footwear and falls: a case involving new cowboy boots.

We present a case in which footwear contributed to a fall that resulted in a severe closed head injury. The woman in this case was wearing new cowboy-style boots with 1.5-inch heels that placed her ankles at a position of 25 degrees plantar flexion. Each boot heel tapered at a 50 degrees angle at its posterior edge. A steel shank protruded 2.5 in posterior to the metatarsal head, serving as the anterior contact surface in lieu of normal metatarsal contact. The design of the boot plus the fact that she was carrying groceries, reduced her ability to regain her balance after she slipped, and she fell backward, hitting the floor with full force on the occiput. Initial computed tomography scan showed large subdural and epidural hematomas and hemorrhagic contracoup contusions. The patient developed clinical signs and symptoms of secondary brainstem injury, which was later substantiated by magnetic resonance imaging scan.

Accidental Falls↗

Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly.

Split hand/split foot (ectrodactyly; SHSF) is a human developmental malformation characterized by missing digits and claw-like extremities. An autosomal dominant form of this disorder has been mapped to 7q21.3-q22.1; the locus has been designated SHFD1. We have constructed a physical map consisting of overlapping yeast artificial chromosome clones for the entire region. Somatic cell hybrid and fluorescent in situ hybridization analyses were used to define SHSF-associated chromosomal rearrangements in twelve patients. An SHFD1 critical interval of 1.5 Mb was established by analysis of five patients with deletions. Translocation or inversion breakpoints found in six patients were mapped within 700 kb of each other in the critical region. Of note is that eight of the patients analyzed (67%) are in fact classified as having syndromic ectrodactyly. Thus, these mapping data establish a relationship between simple split hand/split foot and this more complex group of human birth defects. Finally, we have mapped DLX5, a member of the Distal-less homeobox gene family, to the SHFD1 critical interval.

Abnormalities, Multiple↗

HPV-associated epithelial atypia in oral warts in HIV+ patients.

Reported are oral mucosal warts (HPV common antigen-positive) from 7 adult HIV+ patients in which there was cytologic atypia and disordered growth. Lesions were papillary, white to red in color, and were located on the lip, gingiva, palate, tongue, and buccal mucosa. Histologically, the keratinocytes in the lesions exhibited atypical features in the form of hyperchromatism and karyomegaly. Koilocytes were frequently seen in the upper level keratinocytes where HPV common antigen was identified. The dysplastic areas, which ranged from mild to severe, typically showed abrupt limiting margins. All lesions exhibited intense PCNA reactivity from basement membrane to surface. Nuclei of mid-level and basal keratinocytes of 3 specimens stained positively for p53 protein. We believe that the atypia found in these lesions represents cytologic change that has malignant potential. The subtype of the HPV in these lesions has not yet been determined.

Adult↗

Ease of handling and efficacy of Bricanyl Turbuhaler in Asian asthmatic children.

Ease of handling as well as efficacy of a new terbutaline inhalation device--Bricanyl Turbuhaler--were evaluated among eighty-six Asian children with mild to moderate asthma with a mean age of 8.7 years (range 5 to 14 years) in an open, non-comparative trial. Clinical evaluations were performed on four occasions, ie at the beginning of the run-in period, at the start of the study medication, after 2 weeks of treatment and after a total of 4 weeks of treatment. Appraisal of handling technique was performed by the investigator at the start and end of treatment. Peak expiratory flow rate (PEF) was determined at each visit. Diaries were also kept throughout this time; PEF and asthma symptom scores were recorded every morning and evening. Maximum scores for inhalation technique were achieved by 73% of patients after combined written and verbal instructions at the start of the study and 99% of patients achieved this score at the end of the 4 week treatment period with Bricanyl Turbuhaler. Assessment revealed that approximately 90% of the patients considered loading, inhalation and handling of the Turbuhaler device to be easy, and 90% considered it to be effective in affording symptom relief. Improvements in PEF and reductions in asthma symptoms were observed during the Bricanyl Turbuhaler treatment, as compared to baseline values. All patients tolerated the study medication well without any serious adverse events. We concluded that this group of Asian children were able to use this new "Turbuhaler" device of terbutaline without any difficulty.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Imaging white matter tracts and nuclei of the hypothalamus: an MR-anatomic comparative study.

PURPOSE: To evaluate the MR appearance of the hypothalamus and its associated white matter tracts. METHODS: Coronal and sagittal spin-echo images were obtained in cadaver brains. Gross and histologic sections were made of the cadaver brains. The size, shape, signal intensity, course, and pattern of structures in the hypothalamic region were identified in MR images by comparison with the anatomic sections. RESULTS: The mamillary bodies, paraventricular zone of hypothalamic nuclei, postcommissural fornix, mammillothalamic fasciculus, and anterior commissure were identified on the MR images. CONCLUSION: This study suggests that, with MR imaging of sufficiently high resolution, some of the tracts and nuclei in the hypothalamus may be identified.

Humans↗

5-lipoxygenase-activating protein stimulates the utilization of arachidonic acid by 5-lipoxygenase.

5-Lipoxygenase (5-LO) and its activating protein (FLAP) are both required for cellular leukotriene (LT) synthesis, with 5-LO catalyzing both the synthesis of (5S)-5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HPETE) from arachidonic acid and the subsequent synthesis of LTA4 from 5-HPETE. We have previously expressed both human 5-LO and human FLAP to high levels in Spodoptera frugiperda (Sf9) insect cells, using recombinant baculoviruses. To study the mechanism by which FLAP activates 5-LO, we compared cellular 5-LO activity in Sf9 cells expressing this enzyme to that in Sf9 cells coexpressing FLAP and 5-LO. In this system, FLAP stimulates the utilization of arachidonic acid by 5-LO as a substrate, and increases the efficiency with which 5-LO converts 5-HPETE to LTA4. LT synthesis in cells coexpressing FLAP and 5-LO is inhibited by 3-[1-(p-chlorophenyl)-5-isopropyl-3-tert-butylthio-1H-indol-2-yl]-2,2- dimethyl-propanoic acid (MK-886), an LT biosynthesis inhibitor which specifically binds to FLAP. These studies in Sf9 cells, together with our recent demonstration that FLAP specifically binds arachidonic acid, suggests that FLAP activates 5-LO by acting as an arachidonic acid transfer protein.

5-Lipoxygenase-Activating Proteins↗

5-lipoxygenase-activating protein is an arachidonate binding protein.

5-Lipoxygenase-activating protein (FLAP) is an 18-kDa integral membrane protein which is essential for cellular leukotriene (LT) synthesis, and is the target of LT biosynthesis inhibitors. However, the mechanism by which FLAP activates 5-LO has not been determined. We have expressed high levels of human FLAP in Spodoptera frugiperda (Sf9) insect cells infected with recombinant baculovirus, and used this system to demonstrate that FLAP specifically binds [125I]L-739,059, a novel photoaffinity analog of arachidonic acid. This binding is inhibited by both arachidonic acid and MK-886, an LT biosynthesis inhibitor which specifically interacts with FLAP. These studies suggest that FLAP may activate 5-LO by specifically binding arachidonic acid and transferring this substrate to the enzyme.

5-Lipoxygenase-Activating Proteins↗

Cloning and characterization of a Lambert-Eaton myasthenic syndrome antigen.

Lambert-Eaton myasthenic syndrome is a paraneoplastic neuromuscular disorder in which an immune response directed against a small-cell lung tumor crossreacts with antigens in the neuromuscular junction. To isolate and characterize the antigens, we screened a human fetal brain expression library with a high-titer serum from a patient with Lambert-Eaton myasthenic syndrome. This screening resulted in the isolation of a complementary DNA clone encoding an antigen we call myasthenic syndrome antigen B (MysB). Approximately 43% (3 of 7) of Lambert-Eaton myasthenic syndrome sera specifically recognized MysB fusion protein, whereas none of 34 control sera did. The predicted amino acid sequence of this clone shows a high degree of homology to the beta subunit of calcium channel complexes. The MysB pre-messenger RNA is alternatively spliced to yield 3 forms of the protein differing in the domain between two highly conserved alpha-helical segments.

Antigens↗

Studies of a sperm/placenta cross-reacting antigen, STX-10.

A monoclonal antibody, HSA-10 initially produced against acrosome-reacted human sperm was also shown to cross-react with human placenta/trophoblast. Transmission electron microscopy, as well as indirect immunofluorescent assay, demonstrated that HSA-10 was found to react with antigen on the inner acrosome of human sperm. The cognate antigen, designated as STX-10, was found to exist as an aggregate in the native form when analyzed by Sephacryl S-300 gel filtration chromatography. When purified by HSA-10-immunoaffinity chromatography from human placenta extract, STX-10 was found to be predominantly a group of glycoproteins with a subunit molecular mass in the range of 75 +/- 5 kDa, whereas an additional group of three proteins with subunit molecular mass less than 20 kDa were copurified from human sperm extract. A sandwich enzyme immunoassay was designed to quantitatively determine the immunoactivity of STX-10 in solution, using HSA-10 monoclonal antibody for coating and for signal detection via enzyme conjugation. Based on this assay, it was found that STX-10 could be detected only in human sperm and placenta extract, but not in any other human somatic tissues, such as serum, brain, heart, muscle, kidney and liver. The immunoactivity of STX-10 was found to be sensitive to proteolytic digestion, low pH, in the presence of reducing agent, but resistant to treatment with sodium periodate. This observation suggests that HSA-10 specific epitope is a peptide in nature and not a carbohydrate moiety. Results of antifertility studies revealed that HSA-10 significantly inhibited human sperm penetration to zona-free hamster ova. Thus, the results of this study are consistent with those of WHO Workshop evaluations that seem to suggest that STX-10 is a highly gamete-specific antigen localized on the inner acrosome of human sperm and in human trophoblast/placenta. Therefore, it may play an important role during human fertilization and embryo development.

Animals↗

Molecular identity of a sperm acrosome antigen recognized by HS-63 monoclonal antibody.

The molecular identity of mouse sperm acrosome antigen recognized by HS-63 monoclonal antibody was analyzed by various biochemical, immunological and molecular biological methods. When its cognate antigen, MSA-63 was isolated from mouse testis by immunoaffinity chromatography, a group of protein spots with wide range of molecular sizes and isoelectric points were identified. Through previous studies, it was established that most of these protein spots were actin-like molecules co-purified with MSA-63 protein from mouse testis. To analyze the molecular size heterogeneity of the isolated MSA-63 proteins, rabbit antisera against a computer-predicted antigenic synthetic peptide (amino acid residue No. 160-171) and a recombinant glutathione S-transferase (GST) fusion protein (GST-63) were raised. These two antisera and those raised against the isolated MSA-63 protein were used as the probes in comparative Western blot assay, indirect immunofluorescent assay and enzyme-linked immunosorbent assay (ELISA). Using ELISA, antisera against GST-63 and computer-predicted antigenic synthetic peptides were shown to cross-react with affinity-isolated MSA-63 protein coated on microwells. However, little immunological cross-reactivity was observed between GST-63 fusion protein and the synthetic peptide. By using a Western blot assay, two major protein bands of 22 and 32 kDa, respectively were commonly detected on mouse testis homogenate strips by both anti-MSA-63 and anti-GST-63. In addition, anti-MSA-63 also recognized several protein bands with molecular masses greater than 35 kDa. The results of this study suggested that the molecular heterogeneity of MSA-63 protein isolated from mouse testis and sperm, is due to a series of post-translational modifications on a single gene product. These modifications may include glycosylations, proteolytic digestions and tight non-covalent associations with other testicular cytoskeletal proteins, such as actins.

Acrosome↗

Refined localization and yeast artificial chromosome (YAC) contig--mapping of genes and DNA segments in the 7q21-q32 region.

The chromosome localizations for 159 gene and DNA segments have been refined to one of five intervals in the 7q21-132 region through hybridization analysis with a panel of somatic cell hybrid lines. Seventy-two of these chromosome 7 markers are also mapped on common or overlapping yeast artificial chromosome (YAC) clones. In addition, the breakpoints of chromosome rearrangement contained in five of the somatic cell hybrid lines have been defined by flanking probes within YAC contigs. To provide a framework for further mapping of the 7q21-q32 region, we have established the physical order of a set of reference markers: cen-(COL1A2-D7S15-CYP3A4-PON)-D7S456-(brea kpoint contained in cell hybrid 1EF2/3/K017)-GUSB-D7S186-ASL-(PGY1-PGY3 -GNB2-EPO-ACHE)-D7S238-(proximal breakpoint in GM1059-Rag5)-D7S240-(CUTL1-PLANH1)-(breakp oints in 1CF2/5/K016 and 2068Rag22-2)-(PRKAR2B-D7S13)-LAMB1-(breakpoint in JSR-17S)-DLD-D7S16-MET-WNT2-CFTR-D7S8-tel.

Base Sequence↗

Epstein-Barr virus in acquired immune deficiency syndrome (AIDS) and non-AIDS primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) still occurs mainly in patients who are immunosuppressed, but its incidence is rising dramatically among immunocompetent individuals. The Epstein-Barr virus (EBV) has been detected by in situ hybridization in PCNSL tumor tissue from patients who are immunodeficient, but not from patients who are immunocompetent. Using the more sensitive polymerase chain reaction (PCR) technique, the authors analyzed PCNSL tissue from 13 patients with acquired immune deficiency syndrome (AIDS) and 13 patients who were immunocompetent for the presence of EBV genome. METHODS: DNA was extracted from paraffin-embedded biopsy or autopsy specimens. PCR was run using primers for EBV (from the first internal repeat segment of the EBV genome), and identical samples were run simultaneously with primers against actin or the p53 gene as controls to establish the presence of DNA in the sample. Reaction products were also Southern blotted to confirm EBV specificity. RESULTS: EBV was detected in the tumor tissue of 11 of 13 patients (85%) with AIDS and of 7 of 13 patients (54%) who did not have AIDS. There was a history of illness that might suggest or predispose to immune compromise in 5 of 13 patients without AIDS; however, prior illness did not predict EBV-positive tumors. CONCLUSIONS: Although mechanisms remain to be clarified, EBV was present in a high percentage of patients with AIDS-related PCNSL and non-AIDS-related PCNSL:

Acquired Immunodeficiency Syndrome↗

Zonal distribution of cysteine uptake in the perfused rat liver.

When in situ perfused rat livers were administered tracer or physiologic concentrations of [35S]cysteine, a zone III (perivenous) predominance of uptake was observed in either antegrade or retrograde single-pass perfusion, as determined by quantitative densitometry of autoradiographs of liver section. This pattern remained unchanged from 30 s to 5 min observed. At higher supraphysiologic doses a more uniform acinar distribution of cysteine uptake was observed. Uptake rates of cysteine in antegrade perfusion indicated an apparent saturable component at low but physiologic cysteine concentrations. That uptake rather than metabolic trapping accounts for this perivenular pattern was supported by finding identical zonal distribution under conditions in which GSH and protein synthesis were markedly inhibited. Furthermore, increasing or decreasing hepatic cysteine pool sizes did not affect the extraction or zonation. These results suggest that a low Km transport system for cysteine is localized in zone III of the hepatic acinus.

Animals↗

Coexistent cutaneous T-cell lymphoma and B-cell chronic lymphocytic leukaemia.

Three patients with cutaneous T-cell lymphoma (CTCL) are reported who had concurrent B-cell chronic lymphocytic leukaemia (B-CLL). The separate lineage and clonal nature of the individual lymphoid malignancies were confirmed by gene-rearrangement analysis. The chronology of the illnesses did not support the hypothesis that CTCL predisposes to the development of B-cell proliferative disorders. There was no clear association with immunosuppressive therapy, and HTLV-1 studies were negative in all patients. Consequently, we speculate that a lymphoid stem cell defect, which may lead to the development of either aberrant B- or T-cell clones, may be responsible for such cases of dual lymphoid neoplasia.

Aged↗

Changes in aldose reductase after crush injury of normal rat sciatic nerve.

The response of aldose reductase (AR) to crush injury was studied in normal rat sciatic nerve. Enzyme activity and immunoreactivity of AR were determined at intervals of 1, 5, 14, 28, and 35 days after crush and correlated with histologic and immunocytochemical observations. During nerve degeneration in the distal segments of crushed nerves, a significant reduction in AR activity was detected. At 5 and 14 days, coincident with Schwann cell proliferation, enzyme activity decreased by nearly two- and fourfold, respectively. Although activity of AR increased by 28 days during nerve regeneration, it was not restored to normal levels at 35 days. Similar reductions were observed with the immunoblotting of the enzyme. Quantitative analysis of immunogold labelling on electron micrographs confirmed that proliferating as well as remyelinating Schwann cells contained reduced gold particle density compared to Schwann cells of noncrushed myelinated fibers. Immunoblots of P0, a marker for the degree of Schwann cell differentiation or myelination, showed that the temporal sequence of changes in P0 paralleled that of AR. Thus expression of AR is a function of differentiated or mature Schwann cells. The putative volume regulatory role of AR in Schwann cells may become superfluous during Wallerian degeneration.

Albumins↗