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Biomedical subjects

S F Lin

Publications and source records attributed to S F Lin.

At least 55 records · Page 3Linked to original sources

Clinical manifestations, microbiology and prognosis of 42 patients with necrotizing fasciitis.

Forty-two cases of necrotizing fasciitis (NF) surgically confirmed between January 1991 and October 1995 were retrospectively reviewed. This was done in order to describe the underlying diseases, clinical presentations, etiology and outcome of NF and to assess the prognostic value of a simplified severity scoring system. The system scores changes in consciousness status, body temperature, blood pressure and ventilation to determine the likely outcome of NF. Twenty-five men and 17 women with a median age of 51 years (range, 17-87 yr) were included. Diabetes mellitus (57.1%) was the most common underlying disease. The mean duration of symptoms before admission was 8 days (median, 7 d; range, 1-30 d). The extremities (66.7%) were most commonly involved. Initial clinical presentations within 48 hours of admission included skin erythema and swelling at the affected site (97.6%), pyrexia (61.9%), hypotension (33.3%), altered consciousness (28.6%), bullous lesions (26.2%) and crepitus (9.5%). The mean number of isolated pathogens was 1.8 (range, 0-6). Eight patients had mixed aerobic and anaerobic infections. The attributable case fatality rate was 23.8%. Higher severity score (> or = 4 points), hypotension, altered consciousness, respiratory failure requiring ventilator support, elevation of alanine aminotransferase levels > twofold, serum creatinine > 177 mumol/L, thrombocytopenia (< 100 x 10(9)/L), and worsening symptoms and signs within 48 hours of admission were associated with higher fatality rates (p < 0.05).

Adolescent

Characterization of Epstein-Barr virus DNase and its interaction with the major DNA binding protein.

Bacterially expressed Epstein-Barr virus (EBV) DNase was purified to 98% purity and used as the source for characterization of the enzyme activities. Complete digestion of DNA by EBV DNase yielded 5'-monophosphate nucleosides as the final products. During the logarithmic phase of the reaction, EBV DNase acted processively on dsDNA but distributively on ssDNA. Both 5' to 3' and 3' to 5' exonuclease activities were present, although the former was shown to be 10-fold stronger. No significant discrepancy was seen in the liberation of end-labeled nucleotides by DNase when substrates with 5'-protruding, blunt, or 3'-protruding ends were used. EBV DNase was demonstrated also to have an endonuclease activity using supercoiled plasmid DNA as substrate. Two preferential dsDNA cleavage sites were mapped on pBS-TR, a pBlueScript vector containing one copy of the EBV terminal repeat; both are in vector sequences. Finally, an N-terminally truncated EBV major DNA binding protein, but not EA-D, was shown to inhibit EBV DNase activity. This inhibitory effect may due to direct protein-protein interactions between EBV DNase and the major DNA binding protein. The biological significance of these characteristics is discussed.

Antigens, Viral

Virtual electrodes in cardiac tissue: a common mechanism for anodal and cathodal stimulation.

Traditional cable analyses cannot explain complex patterns of excitation in cardiac tissue with unipolar, extracellular anodal, or cathodal stimuli. Epifluorescence imaging of the transmembrane potential during and after stimulation of both refractory and excitable tissue shows distinctive regions of simultaneous depolarization and hyperpolarization during stimulation that act as virtual cathodes and anodes. The results confirm bidomain model predictions that the onset (make) of a stimulus induces propagation from the virtual cathode, whereas stimulus termination (break) induces it from the virtual anode. In make stimulation, the virtual anode can delay activation of the underlying tissue, whereas in break stimulation this occurs under the virtual cathode. Thus make and break stimulations in cardiac tissue have a common mechanism that is the result of differences in the electrical anisotropy of the intracellular and extracellular spaces and provides clear proof of the validity of the bidomain model.

Animals

Application of ABO genotyping using polymerase chain reaction method to assess engraftment in bone marrow transplantation--a case report.

We described a case of acute promyelocytic leukemia with O blood type who received bone marrow transplantation during a second remission from his HLA identical, B blood type sibling. Using PCR genotyping of the ABO group and analysis of the variable number of tandem repeats of the D1S80 locus, we could quickly document the successful early engraftment in this patient. We emphasize that the use of PCR ABO genotyping is a quick and valuable method which could be applied to assess the engraftment and its follow up in those transplant cases with donors of mismatched blood groups.

ABO Blood-Group System

Clonal analysis in acute myeloid leukemia by polymerase chain reaction.

We have used PCR to amplify a polymorphic portion of the X-chromosome linked phosphoglycerate kinase gene (PGK) combined with a methylation-sensitive restriction enzyme digestion of the active X chromosome to examine the frequency of heterozygosity in Taiwanese females and analyze clonality in 18 female patients with acute myeloid leukemia (AML). We used hair follicles as normal tissue control. We found that the incidence of heterozygosity of the PGK gene in 102 hematological normal females and 18 patients tested was 35% (42/120). In five AML patients, a monoclonal X-inactivation pattern of leukemic blasts was found at presentation, which then returned to polyclonal at remission. In two of these five cases, a monoclonal pattern recurred at relapse. We also found that the hair follicles were readily accessible normal tissue for control, were easy to obtain, and were non-invasive.

Base Sequence

MDR1 gene expression in acute myeloid leukemia: clinical correlation.

Acute myeloid leukemia (AML) has a poor long-term prognosis, with a disease-free survival rate of only 20%. Drug resistance remains the major obstacle in this disease, although relatively little data are available on the correlation of multi-drug resistance (MDR) and clinical outcome. We examined 28 bone marrow samples from 24 patients with AML. The MDR1 RNA levels were determined by slot blot analysis. The incidence of positive expression of MDR1 mRNA in patients was 64.7% in samples from newly-diagnosed patients and 85.7% in relapse samples. The overall complete remission rate was 45%. However, the complete remission rate was lower for patients in the MDR1 RNA positive group than in the negative group. In three cases, the MDR1 RNA expression steadily rose during the period of disease progression and after several courses of chemotherapy. We suggest that a high frequency of MDR1 gene expression in patients with AML and higher MDR1 RNA levels are associated with a lower incidence of complete remission as well as a shorter disease-free time. The expression of MDR1 is a poor prognostic factor for AML treatment and it may play an important role in resistance to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem

Chronic neutrophilic leukemia--a case report.

We describe a 77-year-old patient with chronic neutrophilic leukemia (CNL). Diagnosis of CNL was made by marked increase of mature neutrophils without increased immature granulocytes, splenomegaly and elevated serum vitamin B12 level and by ruling out any infection or occult malignancy. The chromosome analysis showed one abnormal karyotype out of 14 metaphases. The neutrophilic function with nitroblue tetrazolium test revealed impaired phagocytic function in this patient. The neutrophil count became normal gradually after hydroxyurea treatment. However, it still maintained a high percentage of mature neutrophils. Background literature and the prognosis of CNL are discussed.

Aged

[The first successful case or Norwood operation for hypoplastic left heart syndrome in Taiwan].

UNLABELLED: Hypoplastic left heart syndrome is not infrequently seen in Taiwan, but all died previously. An 8 day-old-male baby suffering from hypoplastic left heart syndrome was transferred to our hospital after cardiopulmonary resuscitation. Oral prostaglandin E2 was used to maintain ductal patency and carbon dioxide was used through a respirator to control his pulmonary blood flow. He underwent Norwood operation at age 15 days under deep hypothermia and circulatory arrest. The postoperative course was smooth and occasional tachypnea was controlled by carbon dioxide inhalation through a mask. A follow up echocardiogram showed patent shunt and neoaortic pathway, good interatrial communication and mild tricuspid regurgitation. The baby survived and has fared well 2 years postoperatively. CONCLUSION: We recommend carbon dioxide manipulation before and after the Norwood operation for hypoplastic left heart syndrome with increased pulmonary blood flow uncontrollable by the respirator.

Carbon Dioxide

Autoantigenic proteins that bind recombinogenic sequences in Epstein-Barr virus and cellular DNA.

We have identified conserved autoantigenic cellular proteins that bind to G-rich sequence motifs in recombinogenic regions of Epstein-Barr virus (EBV) DNA. This binding activity, called TRBP, recognizes the EBV terminal repeats, a locus responsible for interconversion of linear and circular EBV DNA. We found that TRBP also binds to EBV DNA sequences involved in deletion of EBNA2, a gene product required for immortalization. We show that TRBP binds sequences present in repetitive cellular DNA, such as variable-number tandem repeats (VNTR) and immunoglobulin heavy-chain class switch regions. We propose that EBV utilizes cellular DNA recombination systems to mediate several types of viral genome alterations. These findings may lead to an understanding of the mechanism of rearrangements of EBV DNA that are a central feature of the biology of the virus.

Animals

Functional analysis of the amino terminus of Epstein-Barr virus deoxyribonuclease.

A cDNA coding for the Epstein-Barr virus (EBV) alkaline deoxyribonuclease (DNase) was expressed in Escherichia coli using the T7 phage system designed to allow expression of potentially lethal proteins. Induction of protein synthesis from the gene yielded a peptide with a molecular weight of approximately 52 kDa, consistent with the predicted open reading frame of EBV BGLF5. A high level of nuclease activity was detected in crude cell extracts, and the activity was neutralized by sera from nasopharyngeal carcinoma patients with high titers of anti-DNase antibodies. A series of deletion clones truncated at the amino or carboxyl terminus was constructed and expressed to define the regions responsible for the nuclease activity of EBV DNase. All the mutated molecules lost their activities even though their expression levels were comparable to that of the full-length DNase. To determine the exact role of the amino terminus of EBV DNase, mutants with small deletions were expressed. While three mutants with deletions of amino acid residues 11-30, 16-28, or 23-28 failed to show any detectable nuclease activities, one mutant in which the first 8 amino acids were replaced by the first 12 amino acid residues of the T7 major capsid protein contributed by the vector was enzymatically active. To further define the importance of the amino-terminal region, full-length DNase with point mutations was generated among residues 23-29 by site-directed mutagenesis and expressed in the same system. Assays of the DNase activity of these mutants revealed that the mutation of residue 29 was fully active, and mutations in 24-27 retained 50% activity. Nevertheless, the mutation at residue 23 resulted in a complete loss of activity and the mutation at residue 28 resulted in loss of 70% activity. These results suggest the biological importance of the amino terminus of the EBV DNase, especially residues 23-28.

Amino Acid Sequence

Molecular basis and hematological characterization of Hb H disease in southeast Asia.

We molecularly characterized sixty-seven cases of Hb H disease by the polymerase chain reaction. The strategy depends on amplifying the alpha-thalassemia-1 (alpha-thal-1) gene by primers flanking the breakpoint and sequence differences of the 3' end of the alpha-globin gene and the nonhomologous elements I, II, and III among different types of alpha-thala-2. In the 67 cases studied, all involved alpha-thal-1 of the Southeast Asia type (SEA) in combination with deletional or nondeletional alpha-thal-2. Thirty-two cases were of the deletion form and 35 cases were of the nondeletion form. In 32 cases of the deletion form, 29 cases were rightward deletion (-alpha 3.7), and three cases were leftward deletion (-alpha 4.2). We found that all of the nondeletion forms were alpha-thal-1 of SEA type with Hb CS. After the subtyping of Hb H with -alpha 3.7, 26 out of 29 were type I deletion and 3 out of 29 were type II deletion. Comparisons of clinical data of deletion forms and the nondeletion form showed that there were earlier occurrence of anemic symptoms and a larger erythrocyte volume in the nondeletion form group (P < 0.005).

Asia, Southeastern

Diagnosis of thalassaemia by non-isotope detection of alpha/beta and zeta/alpha mRNA ratios.

The alpha/beta and zeta/alpha messenger RNA (mRNA) ratios in the thalassaemia syndromes were investigated by polymerase chain reaction (PCR) with silver staining of the PCR products. In this study we used the PCR to amplify cDNA copies of circulating erythroid cell mRNA in order to measure the relative amounts of alpha-, beta- and zeta-globin contained within. Quantitation was performed by scanning the silver stain of specific globin cDNA bands. We found that there were significant differences of alpha/beta-mRNA and zeta/alpha-mRNA in patients with Hb H disease and alpha-thalassaemia-1 compared to normal subjects. There was a marked increase in the alpha/beta-mRNA ratio but not in the zeta/alpha-mRNA ratio in patients with beta-thalassaemia. In two beta-thalassaemia cases abnormal increases of zeta-globin bands were noted and they were confirmed through DNA analysis to be combined with alpha-thalassaemia-1. This method provides a simple, rapid and non-radioactive approach to detect thalassaemia syndromes, and can help to screen cases of beta-thalassaemia with alpha-thalassaemia-1.

Adult

[Rhinocerebral mucormycosis in a case of malignant lymphoma].

Mucormycosis, an uncommon opportunistic fungal infection, usually occurs in immunocompromised patients. It is rapidly progressive and almost always fatal. Patients with lymphoma are susceptible to pulmonary or disseminated mucormycosis, whereas rhinocerebral mucormycosis in such patients, as far as we know, is rarely reported. We present a patient with malignant lymphoma who exhibited such an acute rhinocerebral infection after chemotherapy which manifested initially as a stuffy nose and intractable headache. Then ptosis, proptosis, chemosis and multiple cranial nerve palsies appeared. Eschar was found in the nasal cavity. Direct KOH smear and tissue biopsy revealed mucormycotic infection. He survived because of early diagnosis and prompt treatment.

Brain Diseases

Malignant pheochromocytoma associated with Jaccoud's-type arthropathy, Raynaud's phenomenon, positive antinuclear antibody and rheumatoid factor.

We describe a patient with malignant pheochromocytoma who developed Jaccoud's-type arthropathy and Raynaud's phenomenon as initial manifestations of malignant pheochromocytoma. Serologic findings included positive antinuclear antibody (ANA) and rheumatoid factor (RF) was also found in this patient. To our knowledge, this is the first time Jaccoud's-type arthropathy with positive ANA and RF has been reported as rheumatic manifestations of pheochromocytoma.

Adrenal Gland Neoplasms

Effects of laser-induced hyperthermia treatment on ionic permeability of myelinated nerve.

The effect of laser-induced hyperthermia on the ionic permeability of nerve membranes was studied using the nodes of Ranvier in amphibian myelinated nerve as a model. To effect a photothermal modification of nerve membrane functions, controlled laser irradiation consisting of a 5-sec thermal pulse was applied to the nodal membrane, increasing the temperature to a maximum of 48-58 degrees C at the node. Major electrophysiological changes observed in the nodal membrane following laser-induced hyperthermia were a differential reduction of the sodium and potassium permeability, an increase in the leakage current, and a negative shift on the potential axis of the steady-state Na inactivation. There was no significant change in the kinetics of ion channel activation and inactivation for treatments below 56 degrees C. The results suggest that a primary photothermal damage mechanism at temperatures below 56 degrees C could be a reduction in the number of active Na channels in the node, rather than a change in individual channel kinetics, or in the properties of the lipid bilayer of intervening nerve membrane. A differential heat sensitivity between the noninactivated and the inactivated Na channels is also suggested. For the treatments of 56 degrees C and above, a significant increase of membrane leakage current suggests an irreversible thermal damage to the lipid bilayer.

Animals

The effects of Chinese herbs on improving survival and inhibiting anti-ds DNA antibody production in lupus mice.

Systemic lupus erythematosus (SLE) is an important autoimmune disease with multiple organ system involvement. From preliminary studies, we have found that six Chinese herbs: Atractylodes ovata, Anqelica sinensis, Cordyceps sinensis, Liqustrum lucidum, Codonopsis pilosula and Homo sapiens can improve defective in vitro interleukin-2 (IL-2) production in patients with SLE. In order to investigate the in vivo effects of these herbs, we used NZB/NZW F1 mice, a typical lupus animal model used to test these herbs. It was found that C. pilosula, H. sapiens and C. sinensis could prolong the life span of female NZB/NZW F1 mice and inhibited anti-ds DNA production. Although A. sinensis could prolong the life span of experimental mice, it did not inhibit the production of anti-ds DNA antibody. These herbs may have great potential for the management of human SLE in the future.

Animals