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Biomedical subjects

L H Chow

Publications and source records attributed to L H Chow.

At least 37 records · Page 2Linked to original sources
PubMed1996

Processing of chimeric antisense oligonucleotides by human vascular smooth muscle cells and human atherosclerotic plaque. Implications for antisense therapy of restenosis after angioplasty.

BACKGROUND: Antisense oligonucleotides have been used in animals to inhibit the accumulation of vascular smooth muscle cells (VSMCs) after arterial injury. This has raised prospects for an oligonucleotide-mediated approach to prevent restenosis in patients undergoing angioplasty. However, little is known about the processing of oligonucleotides by human VSMCs or their bioavailability in human atherosclerotic tissue. METHODS AND RESULTS: Oligonucleotides were synthesized with a mixture of unmodified and sulfur-modified linkages (S-chimeric oligonucleotides). These were more stable than unmodified oligonucleotides and could be recovered from within human VSMCs after 36 hours. Oligonucleotide antisense to human proliferating cell nuclear antigen mRNA specifically reduced DNA synthesis (P < .01) and proliferating cell nuclear antigen protein content (P < .05) in human VSMCs. Confocal microscopy of both live and fixed cells showed modest oligonucleotide uptake that was primarily nuclear. Surprisingly, cationic liposomes did not enhance nuclear uptake but led to extensive, punctated cytoplasmic loading without an enhanced antisense effect. Oligonucleotides incubated with human coronary atherosclerosis fragments associated with cells within 1 hour, despite the presence of abundant extracellular matrix. CONCLUSIONS: S-chimeric oligonucleotides are stable and can specifically inhibit gene expression in human VSMCs. Nuclear transport is a feature of oligonucleotide processing by human VSMCs, indicating a potential influence at the nuclear level rather than with cytoplasmic mRNA. Cationic liposomes increased oligonucleotide uptake but not intracellular bioavailability, and S-chimeric oligonucleotides can be incorporated into cells within human atherosclerotic plaque, despite the presence of a dense extracellular matrix.

Angioplasty↗
PubMed1996

EMG spike trains of succinylcholine-induced fasciculations in myalgic patients.

Single spike activity from the surface electromyogram (EMG) of fasciculations induced by succinylcholine (Sch) were studied from limb muscles (biceps, triceps, anterior tibialis and gastrocnemius) in 100 female patients. About 2/3 of them (n = 72) also received nondepolarizing neuromuscular pretreatment (atracurium or vecuronium). We observed from 20% of EMG records in the myalgic (but not in the nonmyalgic) patients, sustained spike trains (mean duration 1.47 s) that resembled motor units firing at physiologically high rates (mean 21.7 spikes/s). The finding reflects Sch's distal actions at the muscle spindle. The implications for myalgia and the possible involvement of micro damage at the extrafusal muscles are discussed.

Action Potentials↗
PubMed1995

Latissimus dorsi dynamic cardiomyoplasty: role of combined ICD implantation.

Latissimus dorsi cardiomyoplasty is a promising surgical therapy in some patients with congestive heart failure. Although the mortality in heart failure patients is attributable primarily to heart failure and ventricular arrhythmias, the mechanism of death after cardiomyoplasty is not well characterized. We describe the clinical course of a patient undergoing cardiomyoplasty and discuss the role of combined use with an implantable cardioverter defibrillator. A 39-year-old man with congestive heart failure due to a massive anterior wall myocardial infarction was evaluated for latissimus dorsi cardiomyoplasty. The patient was in NYHA Functional Class III due to heart failure. He did not have any significant exertional or rest angina. During a Naughton stress test, the patient could exercise for 10 minutes, achieving 4 METS. Pulmonary function study showed a peak V O2 of 22.1 mL/min per kg. Radionuclide angiography demonstrated that the anterior wall was akinetic with a left ventricular ejection fraction of 22%. Cardiac hemodynamic studies suggested moderate pulmonary hypertension, elevated wedge pressure, and suboptimal response to exercise. A Holter recording showed frequent ventricular extrasystoles. Cardiomyoplasty was preferred to heart transplantation because the patient did not have end-stage heart failure. Postoperatively, the patient required low doses of dopamine. He developed recurrent, sustained, and hemodynamically significant episodes of ventricular tachycardia. He was treated with a combination of amiodarone and procainamide. He died 2 days postoperatively with ventricular fibrillation. Ventricular arrhythmias are a major cause of death in patients with heart failure. Latissimus dorsi cardiomyoplasty appears to be a promising but unproven therapy in such patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Endothelin receptor mRNA expression in renal medulla identified by in situ RT-PCR.

Three subtypes of endothelin (ET) receptors have been identified by cDNA cloning, namely ET-RA, ET-RB, and ET-RC. In the current study the precise cellular distribution of the ET receptor subtypes in the renal medulla was explored by detecting the corresponding polymerase chain reaction (PCR)-amplified cDNAs by in situ reverse transcription (RT)-PCR. The PCR-amplified cDNAs were detected either by direct incorporation using digoxigenin-dUTP (dig-dUTP) as a nucleotide substrate in the PCR reaction or by in situ hybridization with the dig-dUTP-labeled probe. ET-RB mRNA was detected exclusively in the epithelial cells of the inner and outer medullary collecting duct. In contrast, ET-RA message was observed primarily in interstitial cells and pericytes of the vasae rectae in the outer and inner medulla. Southern blot analysis of PCR-amplified cDNAs reverse transcribed from extracted RNA of rat renal medulla confirmed the specificity of the RT-PCR products. ET-RC mRNA was not detected. We conclude that ET-RB is the major ET receptor found in rat renal medulla and is expressed exclusively on inner medullary collecting duct cells. The pattern of ET receptor mRNA expression described suggests different physiological actions for ET on the diverse cellular structures of the renal medulla.

Animals↗
PubMed1995

Vecuronium dissolved in normal saline exaggerates pain on intravenous injection.

BACKGROUND: On some anesthetic occasions, many patients complained of pain at the site of injection when vecuronium, dissolved in normal saline, was administered intravenously. The aims of this study was to compare the incidence of pain on i.v. injection of vecuronium either dissolved in normal saline or in a solvent provided by the pharmaceutical manufacturer. METHODS: We studied eighty patients of ASA physical status class I-II undergoing elective surgery under general anesthesia. Patients were arranged randomly to receive intravenous 0.1 mg/kg vecuronium dissolved either in solvent (n = 40) or in normal saline (n = 40) through the catheter indwelling in a vein on the dorsum of hand over 5 seconds. Immediately after injection, a nurse was appointed to score the degree of pain. Induction of anesthesia was accomplished with thiopental and fentanyl 30 seconds after vecuronium administration. RESULTS: Vecuronium dissolved in normal saline induced severe pain more frequently during injection than that dissolved in solvent (27.5% versus 10%). There was no significant difference in pH between these two solutions (3.87 versus 4.08). However, vecuronium dissolved in normal saline showed higher osmolality than that dissolved in solvent (425 +/- 7 mOsm/kg versus 149 +/- 3 mOsm/kg). CONCLUSIONS: Pain resulting from intravenous injection of vecuronium can be aggravated if normal saline was used as the solvent. Increased osmolality may also be responsible for this phenomenon.

Adult↗
PubMed1995

Acquired long QT syndrome in a child undergoing craniotomy: a case report.

The long QT syndrome (LQTS) is a rare disorder of cardiac conduction in children. It may lead to severe arrhythmia, syncope or sudden death. Electrolyte disturbance and the use of procainamide are closely related to the acquired LQTS. This report concerns a fatality of acquired LQTS in a boy undergoing craniotomy. After induction of anesthesia, his electrocardiogram displayed a frequent torsade de pointes type of ventricular tachycardia with prolonged QT interval. Therefore, congenital LQTS was impressed. However, the arrhythmia was aggravated by intravenous propranolol. Isoproterenol infusion was given under the diagnosis of acquired LQTS. The arrhythmia was successfully abolished and a stable hemodynamic status was maintained. However, the child could not tolerate the anesthesia which lasted for 30 hours, and eventually succumbed, despite aggressive treatment and resuscitation attempts. Differential diagnosis between the types of LQTS should be made promptly. This may be of paramount importance in the outcome since prognosis depends upon proper treatment. This case report discusses the etiology and management of this rare abnormality.

Child↗
PubMed1993

Verification of endotracheal tube misplacement with the colorimetric carbon dioxide detector during anesthesia.

The sensitivity and reliability of the colorimetric end-tidal carbon dioxide detector (CETCO2) in verifying misplacement of endotracheal tube in the esophagus were assessed during induction of anesthesia using a conventional capnograph as control. Sixty patients of ASA physical status I and II undergoing elective minor surgery had their anesthesia induced with thiopental sodium (4-5 mg/kg, i.v.). Oral endotracheal intubation facilitated with succinylcholine (1.0 mg/kg, i.v.) was performed by junior residents. The time required for the appearance of discoloration from purple (< 2.5 torr) to tan-hued (3.8-7.6 torr) or yellow (> 15.2 torr) on the CETCO2 (T1) was significantly shorter (3.83 +/- 0.92 second vs. 8.23 +/- 1.14 second, p < 0.01) as compared with the initial display of the ETCO2 waveform on the capnograph (T2). Out of 60 patients esophageal intubation occurred in 6 (10%). Two patients had the color of the CETCO2 changing from purple to tan-hued at the first breath but reverting to purple at the 2nd or 3rd breath. Thus, the sensitivity of CETCO2 was 97.0% (3.0% false positive) if the first breath was chosen as the point of determination. However, if it was set at the 6th breath or yellow was chosen as the color of determination, the sensitivity increased to 100% without either false positive or false negative. In conclusion, the CETCO2 detector is reliable for the detection of correct placement of endotracheal tube during induction of anesthesia, no matter whether Jackson-Rees modification Ayre's T-piece or anesthetic breathing circuit is used for ventilation.

Adolescent↗
PubMed1993

Studies of virus-induced myocardial injury in mice: value of the scid mutation on different genetic backgrounds and combined with other mutations.

The mechanism of cardiac muscle damage in virus-induced myocarditis remains to be fully understood. In particular, a direct role for viral replication has been obscured by evidence of immune-mediated injury. The combined use of severe combined immunodeficient (scid) and doubly mutant scid/beige mice of different genetic backgrounds has provided a unique opportunity to study the consequences of viral proliferation apart from the influence of immunologic responses. In these immunodeficient animals, inoculation with coxsackievirus B3 caused severe myocardial injury, indicating a profound and direct pathogenic potential of viral infection. These studies, in turn, serve to illustrate the value of the scid mutation in experimental biology, as defined among different genetic backgrounds and combined with other mutations.

Animals↗
PubMed1992

Enteroviral infection of mice with severe combined immunodeficiency. Evidence for direct viral pathogenesis of myocardial injury.

Inbred mice with genetically determined severe combined immunodeficiency (SCID) lack mature T and B lymphocyte functions. To distinguish direct viral effects in the pathogenesis of myocarditis from those mediated by antigen-specific and histocompatibility-complex-restricted host immunity, we inoculated coxsackievirus B3 into homozygous young adult SCID mice. We found that infected SCID mice invariably developed extensive myocarditis between 7 and 14 days postinoculation with high subsequent mortality. Histopathologic examination of the infected SCID myocardium indicated multiple foci of cardiomyocyte necrosis and a delayed pleomorphic inflammatory infiltrate. Immunohistochemically, the coxsackievirus B3-infected SCID heart contained frequent clusters of macrophages (Mac-1+) as well as other cells that may represent nonspecific phagocytic or cytolytic effectors. In situ hybridization with radiolabeled cDNA probes for enteroviral genome indicated a significant excess of positive-strand genome in the SCID myocardium compared with that in similarly infected non-SCID controls, with hybridization signals localized primarily to cardiomyocytes. In vitro culture confirmed persistent viremia and a vast excess of infective virus in the SCID myocardium relative to infected non-SCID controls. Thus, direct viral mechanisms in the production of cardiomyocyte injury in coxsackievirus B3-infected mice appear to be more important than previously recognized, particularly in the setting of unrestricted viral proliferation.

Animals↗
PubMed1992

Interpleural administration of bupivacaine for postoperative analgesia after thoracotomy in patients with patent ductus arteriosus.

Interpleural analgesia for postoperative pain with bupivacaine 0.25%, 0.375% and 0.5% at dosage of 1.5 mg/kg was evaluated in three randomized groups (A, B and C) of 22 children having triple ligation for patent ductus arteriosus (PDA). Complete pain relief was obtained within 30 min irrespective of the concentration of bupivacaine. The duration of pain relief significantly varied with the concentrations of the drug used, respectively 5.02 +/- 0.4 h, 6.88 +/- 0.7 h and 8.24 +/- 1.08 h (mean +/- SD) for 0.25%, 0.375% and 0.5% bupivacaine (p less than 0.05). No side effects were observed and no other supplemented narcotics were given. We concluded that 0.5% bupivacaine at the dose of 1.5 mg/kg was effective in postoperative pain relief after thoracotomy in patients undergoing PDA ligation surgery.

Adolescent↗
PubMed1991

Progress and challenges in the pathological diagnosis of myocarditis.

The pathological diagnosis of myocarditis rests on well-described histopathological criteria. Appreciation for the disease-specific sensitivity of the endomyocardial biopsy, as well as the phenotypical and functional nature of inflammatory infiltrates, will enhance the clinical utility of the biopsy technique. New information regarding the role of enteroviruses in immunological sensitization and the study of enteroviruses in murine models and human patients are fostering new perspectives and routes of investigation of appropriate therapeutic interventions for myocarditis.

Animals↗
PubMed1991

Susceptibility to Coxsackievirus B3-induced chronic myocarditis maps near the murine Tcr alpha and Myhc alpha loci on chromosome 14.

This study was undertaken to determine the genetic control of host susceptibility to coxsackievirus B3 (CVB3)-induced chronic myocarditis in a mouse model. An autosomal recessive autoimmune myocardial disease (amd) gene (possibly more than one gene), which determined susceptibility to CVB3-induced chronic myocarditis in the A/J and DBA/2J inbred mouse strains, was mapped to a segment of chromosome 14. Data from both the AXB/BXA recombinant inbred (RI) strains and the B10.D2(57N) H-8b congenic mice supported this linkage relationship. Analysis of the AXB/BXA RI strain distribution patterns suggested that amd maps distal to the Np-2, Tcr alpha, and Myhc alpha loci.

Animals↗
PubMed1991

Differential effects of myocarditic variants of Coxsackievirus B3 in inbred mice. A pathologic characterization of heart tissue damage.

The histopathologic features reflecting the influence of virus genotype and host differences on myocarditis were evaluated in six inbred mouse strains (C57BL/6, B10.D2, BALB/c, DBA/2, A/J, and C3H/HeJ) inoculated with four respective variants of coxsackievirus B3 (CVB3-CG, -SH, -ST, or -NR). The most severe and most prevalent histologic lesions occurred after infection with CVB3-SH or -CG variants, regardless of mouse strain. In general, C57BL/6 mice showed the lowest susceptibility to myocarditis while A/J or C3H/HeJ animals had the highest susceptibility, whether early (7 days) or late (21 days) after CVB3 inoculation. Lesion size and calcification depended to an extent on disease severity, but calcification in the C3H/HeJ myocardium was notably sparse. Lesions clustered distinctly in the midthird of the ventricular wall in some animals, particularly in DBA/2 mice. Extensive pericarditis occurred exclusively in BALB/c and DBA/2 animals and predominated over the right ventricle anterolaterally. Virus titer in the heart did not account for disease susceptibility among mouse strains. These characteristics reflect differences in pathogenicity and are important considerations in the study of mechanisms in CVB3-induced myocarditis in mice.

Animals↗
PubMed1991

Progressive cardiac fibrosis and myocyte injury in v-fps transgenic mice. A model for primary disorders of connective tissue in the heart?

Transgenic mice that express v-fps protein-tyrosine kinase have severe cardiac or neurologic abnormalities and a high incidence of lymphoid or mesenchymal tumors. The cardiac lesions of v-fps transgenic mice were examined at less than 1, 2, 3, 6, 14, 26, and 43 weeks of age (total N = 19) and compared with nontransgenic littermate controls (N = 34). Three of eight transgenic animals 1 to 4 days old showed moderate proliferation of connective tissue elements most evident along the septal endocardium of the right ventricle. Variable cardiac hypertrophy was seen grossly in 2- to 14-week-old transgenic animals, and marked biventricular dilatation was present in those 6 to 43 weeks of age. Sections of all transgenic mice 3 weeks or older revealed characteristic lesions that consisted of cellular fibrosis in subendocardial, subepicardial, and perivascular sites, with associated proliferation of pericytes and fat cells. Atrophy, degeneration, and loss of entrapped myocytes were noted in transgenic animals as early as 2 weeks of age, but frank coagulative necrosis or myocytolysis was absent at all ages studied. Nonetheless, pleomorphic nuclei were found in occasional myocytes late in disease. Inflammatory cells were rare, as confirmed immunohistochemically (Thy-1 [pan-T], L3T4 [CD4], Lyt-2 [CD8], interleukin-2 receptor [activated lymphocyte], Mac-1 [macrophage], and B220 [pan-B]). Monoclonal immunoreactivity to the v-fps transgene product was positive predominantly in nonmyocyte cardiac constituents. Collectively, the data suggest a primary proliferative abnormality of connective tissue elements in the heart, accompanied by secondary myocyte damage.

Aging↗
PubMed1990

The cDNA sequences encoding two components of the polymeric fraction of the intracellular hemoglobin of Glycera dibranchiata.

The intracellular hemoglobin of the polychaete Glycera dibranchiata consists of several components, some of which self-associate into a "polymeric" fraction. The cDNA library constructed from the poly(A+) mRNA of Glycera erythrocytes (Simons, P. C., and Satterlee, J. D. (1989) Biochemistry 28, 8525-8530) was screened with two oligodeoxynucleotide probes corresponding to the amino acid sequences MEEKVP and AMNSKV. Each of the two probes identified a full-length positive insert; these were sequenced using the dideoxynucleotide chain termination method. One clone was 630 bases long and contained 36 bases of 5'-untranslated RNA, a reading frame of 441 bases coding for the 147 amino acids of globin P2 including the residues MEEKVP, and a 3'-untranslated region of 153 bases. The other clone was 540 bases long and contained 24 bases of 5'-untranslated RNA, an open reading frame of 441 bases coding for globin P3 including the residues AMNSKV, and a 3'-untranslated region of 75 bases. The inferred amino acid sequences of the two globins were in agreement with the partial amino acid sequences obtained by chemical methods. The P2 and P3 globin sequences, together with the previously determined P1 sequence of a complete insert and partial sequences P4, P5, and P6 obtained from partial inserts (Zafar, R. S., Chow, L. H., Stern, M. S., Vinogradov, S. N., and Walz, D. A. (1990) Biochim. Biophys. Acta, in press) suggest that there are at least six components in the polymeric fraction of Glycera hemoglobin, which is in agreement with the results of polyacrylamide gel electrophoresis in Tris/glycine buffer, pH 8.3, 6 M urea. Nothern and dot blot analyses of Glycera erythrocyte poly(A+) mRNA using the foregoing two cDNA probes clearly demonstrated the presence of mature messages encoding both types of globins. Comparison of the polymeric sequences P1, P2, and P3 with the "monomeric" globins M-II and M-IV using the alignment and templates of Bashford et al. (Bashford, D., Chothia, C., and Lesk, A. M. (1987) J. Mol. Biol. 196, 199-216) showed that all five globins have identical residues at 39 positions. At 44 positions, the three polymeric globins share identical residues that differ from the identical residues at the corresponding locations in the monomeric sequences M-II and M-IV including position E7, where the latter have leucine instead of the distal histidine. At 15 positions, there occurs an alteration from polar to nonpolar or from a small nonpolar to a larger nonpolar residue in going from the monomeric to the polymeric globins.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1990

The heterogeneity of the polymeric intracellular hemoglobin of Glycera dibranchiata and the cDNA-derived amino acid sequence of one component.

The erythrocytes of the marine polychaete Glycera dibranchiata contain a number of different, single-chain hemoglobins, some of which self-associate into a 'polymeric' fraction. An oligodeoxynucleotide probe was synthesized based on partial amino acid sequences determined by chemical methods, and used to screen a cDNA library constructed from the poly(A+)mRNA of Glycera erythrocytes (Simons, P.C. and Satterlee, J.D. (1989) Biochemistry 28, 8525-8530). The longest positive inserts found were sequenced using the dideoxy nucleotide chain termination method. One complete clone was obtained: clone 5A, 816 bases long, contained 59 bases of 5'-untranslated RNA, an open reading frame of 441 bases coding for 147 amino acids and a 3'-untranslated region of 316 bases. The derived amino acid sequence of Glycera globin P1 was in agreement with the partial amino acid sequences obtained by chemical methods. Three additional inserts obtained in the screening were also sequenced: the inferred amino acid sequences proved to be partial globin sequences which were different from each other and from the sequence of P1. Thus, the 'polymeric' fraction of the intracellular hemoglobin of Glycera probably consists of at least four different globin chains much like the 'monomeric' fraction. Comparison of the 'polymeric' sequence with the two known 'monomeric' sequences, M-II and M-IV, shows that they share 54 identical residues. At 74 positions, the identical residues in M-II and M-IV differ from the corresponding residue in P1, including at E-7, where P1 has a distal His, in contrast to Leu in M-II and M-IV. The alignment of Bashford et al. ((1987) J. Mol. Biol. 196, 199-216) and their templates were used to examine the principal differences between the two types of Glycera globin sequences. They appear to consist of uncommon surface amino acid residues at positions C6 (Phe vs. Ala), E10 (Val vs. Lys), E17 (Lys vs. Val), G1 (Arg vs. Lys), G10 (Met vs. Ala) and H5 (Arg vs. Lys). One or more of these residues could be responsible for the self-association exhibited by the 'polymeric' Glycera globins.

Amino Acid Sequence↗