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Biomedical subjects

S K Liu

Publications and source records attributed to S K Liu.

At least 37 records · Page 2Linked to original sources

Sustained attention deficit and schizotypal personality features in nonpsychotic relatives of schizophrenic patients.

OBJECTIVE: The authors investigated whether nonpsychotic relatives of schizophrenic probands have an elevated risk of deficits in sustained attention as measured by the Continuous Performance Test (CPT), whether such deficits are associated with specific factors of schizotypy, and whether poor CPT performance by probands predicts poor performance by their relatives. In addition, the heritability of CPT performance in the families of schizophrenic probands was estimated. METHOD: The study subjects were 60 schizophrenic probands, 148 of their first-degree relatives, 20 normal comparison probands, and 42 of the comparison probands' first-degree relatives. Subjects completed undegraded and 25% degraded sessions of the CPT and were interviewed with use of the Chinese version of the Diagnostic Interview for Genetic Studies. Subjects' CPT sensitivity indexes, d', were standardized against those of a community sample of 345 subjects, with adjustment for age, sex, and level of education. RESULTS: On average, the d' values of the relatives of schizophrenic probands were lower than those of the relatives of comparison probands but higher than those of schizophrenic probands. Lower sensitivity indexes among the relatives of schizophrenic patients were associated with the interpersonal dysfunction and disorganization factors of schizotypy but not the cognitive/perceptual factor. When schizophrenic probands were divided into two subgroups by a cutoff of -3.0 for adjusted z score on the CPT, the d' values of relatives of probands with CPT deficits were lower than those of relatives of probands without deficits. The estimated heritability of performance on the CPT ranged from 0.48 to 0.62. CONCLUSIONS: Sustained attention deficit may be a genetic vulnerability marker for schizophrenia, and it may be more useful in linkage analysis than traditional phenotype definitions of schizophrenia.

Adult↗

Clinical symptom dimensions and deficits on the Continuous Performance Test in schizophrenia.

We examined the relationships between symptom dimensions derived from factor analytic studies of schizophrenic symptoms and sustained attention deficits. Four factors, negative, delusion/hallucination, disorganization, and excitement, were yielded from factor analysis on 14 items of the Positive and Negative Syndrome Scale (PANSS) among 60 Chinese inpatients with acute schizophrenia. The negative dimension was associated with lower sensitivity index (d') while the excitement dimension was associated with higher d' on the Continuous Performance Test (CPT) after sex, age and education were adjusted for in multiple linear regressions. The positive dimension affected only response criterion (ln beta) and was not associated with the d' on the CPT. In contrast, the summed scores of PANSS Positive and Negative scales did not have significant correlations with d' on the CPT. Thus, the discriminant validity of these symptom dimensions of schizophrenia is supported by their correlations with CPT performance indices.

Acute Disease↗

Operation in patients with incurable colon cancer--is it worthwhile?

PURPOSE: This study was designed to identify objective criteria that might help surgeons decide which patients with incurable colon cancer will benefit from palliative surgery and which will not. METHODS: Charts of 68 patients with incurable colon cancer were reviewed. Fifty-seven patients underwent resection, six had a bypass of a nonresectable cancer, and five had no surgery at all. Time to death was the major end point of the study. Minor end points were postoperative morbidity and mortality. Independent variables analyzed were comorbidity, preoperative carcinoembryonic antigen, liver function tests, extent of liver metastases, stage and site of tumor, and tumor cell differentiation. RESULTS: There were six postoperative deaths, and six patients had complications. Mean survival after palliative resection was 10.6 months, after bypass was 3.4 months, and after diagnosis in patients not operated on was 2 months. Patients with > 50 percent of their liver replaced by cancer had significantly worse survival than those with < 50 percent involvement (mean, 4.2 +/- 4 standard deviation (SD) vs. 14.4 +/- 10.6 SD; P < 0.003, Wilcoxon's rank-sum test). Tumor differentiation also influenced survival (poor, mean 8.4 +/- 8.2 SD; well/moderate, 12.5 +/- 9.2 SD; P < 0.02). No other variable had a significant effect on survival. CONCLUSION: Resection of primary colon cancer in patients with incurable disease has a relatively high postoperative mortality but is worthwhile as long as hepatic metastases occupy less than 50 percent of liver volume.

Aged↗

Preferential mutagenesis of lacZ integrated at unique sites in the Escherichia coli chromosome.

To study the variation in spontaneous mutation frequencies in different chromosomal domains, a mini-Mu-kan-lacZ- transposable element was constructed to insert the lacZ-(Trp570 --> Opal) allele into many different loci in the Escherichia coli chromosome. Papillation on MacConkey lactose plates was used to screen for mini-Mu insertion mutants with elevated levels of spontaneous mutagenesis of lacZop --> LacZ+; candidates were then screened for normal mutation frequencies in other genes. Two different insertion mutants with this enhanced mutagenesis phenotype were isolated from 14000 colonies, and named plm-1 (preferential lacZ mutagenesis) and plm-2. The frequency of LacZ- --> LacZ+ mutations in these plm mutants was over 400-fold higher than that in isogenic strains containing mini-Mu-kan-lacZop insertions at other loci. Six Lac+ reversion (or suppression) mutations obtained from each of the two plm mutants were mapped by P1 transduction and all were found to be linked to the Kan(r) gene in the mini-Mu-kan-lacZop, suggesting that a localized mutagenic event is responsible for the preferential mutagenesis. Furthermore, both the LacZ+ --> LacZ- and Kan(r) --> Kan(s) mutant frequencies of these Lac+ revertants were in the range of 10(-3) to 10(-2), indicating that this putative localized mutagenesis is neither allele nor gene specific. To identify the plm loci, the chromosomal regions flanking the mini-Mu insertion sites were cloned and sequenced. A computer-assisted database search of homologous sequences revealed that the plm-1 locus is identical to the mutS gene; the mini-Mu insertion most probably results in the production of a truncated MutS protein. We suggest that the enhanced lacZ mutation frequency in plm-1 may be associated with an active process involving the putative truncated MutS protein. The DNA sequence of the plm-2 locus matched a putative malate oxidoreductase gene located at 55.5 min of the E. coli chromosome.

Alleles↗

Intramural coronary artery disease in swine with naturally occurring hypertrophic cardiomyopathy.

Intramural coronary artery disease (ICAD) has been reported in myocardium affected with hypertrophic cardiomyopathy (HCM), but has never been studied in detail with respect to the cell type or lipid infiltration involved in the wall-thickening. The lack of heart samples may be one of the rationales to hamper the progress in investigating this disease. Recently, the discovery of naturally occurring HCM in swine has provided an excellent opportunity for the study of ICAD because of the high prevalence of ICAD in this animal. The present study provides a detailed structure feature in the thickened arterial wall of ICAD by both histologic and electron microscopic means. Morphologically, the feature of ICAD is due primarily to the neointimal thickening. Smooth muscle cells (SMC) and extracellular matrix (collagen and elastic fibers) are the major components responsible for the thickened neointima. Fragmentation of the internal elastic membrane is associated with the migration and proliferation of SMC from the media to the intima. Therefore, pigs with HCM may be a potential animal model not only for the study of the mechanism by which SMC migrate and proliferate into intima, but also for the future investigation of interventions in coronary artery occlusion.

Animals↗

Rickets in a 6-month-old monkey.

A 6-month-old male monkey with rickets was found dead by its keeper. Radiographic studies showed osteopenia of the entire skeletal system, a cup-shaped concavity and poor mineralization of metaphyseal ends, and markedly widened and irregular epiphyseal growth plates of the long bones and ribs. Gross anatomic findings included bowing abnormalities and microfractures in the radius, ulna, tibia, and fibia, and enlarged and widened cartilage columns extending into the metaphyses in the long bones and ribs. Histologic features included deficient mineralization and irregular disordered columns of proliferating cartilage in growth plates extending into other zones, dilated vascular channels, and poor mineralization of chondroid and osteoid tissues.

Animals↗

Substantial decrease of heat shock protein 90 in ventricular tissues of two sudden-death pigs with hypertrophic cardiomyopathy.

We recently developed a pig model with naturally occurring hypertrophic cardiomyopathy (HCM). To further characterize the biochemical features of high frequency of sudden death affected by this disease, the protein profiles of ventricular tissues were analyzed on normal, HCM, and HCM with sudden-death pigs. By sodium dodecylsulfate-polyacrylamide gel electrophoresis, a protein corresponding to an apparent molecular mass of 90 kDa (p90) was found to be markedly decreased in the HCM-affected tissues of sudden-death pigs, but not in HCM or normal pigs. Further study showed that the primary decrease of p90 in HCM pigs with sudden death was located mainly in the interventricular septum. As determined by the molecular mass and isoelectric point on 2-dimensional gels and Western immunoblot with a specific 90 kDa heat shock protein (HSP90) monoclonal antibody, the unknown protein was identified as HSP90. Our findings indicate for the first time that substantially decreased heart HSP90 is associated with HCM pigs with sudden death. Although the role that HSP90 may play in protecting pigs with HCM from sudden death is still nuclear, the model itself may provide further insight into understanding the role of heat shock proteins in cardiac sudden death.-Lee, W.-C., Lin, K.-Y., Chiu, Y.-T., Lin, J.-H., Cheng, H.-C., Huang, H.-C., Yang, P.-C., Liu, S.-K., Mao, S. J. T. Substantial decrease of heat shock protein 90 in ventricular tissues of two sudden-death pigs with hypertrophic cardiomyopathy.

Animals↗

Heritability estimate of hypertrophic cardiomyopathy in pigs (Sus scrofa domestica).

The purpose of this study was to evaluate the heritability of hypertrophic cardiomyopathy (HCM) in pigs and the relation between HCM and heart measurements, pathologic features, and growth to provide references for HCM line development. A total of 353 on-farm tested gilts (females) and boars (males) from 74 sire families were randomly selected from a single breeding farm where HCM was prevalent. Hearts were collected after animals were slaughtered. Heart length, width, and weight, heart-to-body weight ratio, and thickness of the cranial, middle, and caudal portions of the ventricular septum, left and right ventricles, and apex were measured. Cardiac hypertrophy and myocyte disorganization, myocardial and endocardial fibrosis, and intramural coronary arterial occlusion were used as criteria for HCM. Growth traits were evaluated from average daily body weight gain, ultrasonically determined backfat thickness, loin-eye area, and performance selection index. Heritability of the disease was estimated by treating it as a threshold trait. The prevalence of HCM in three studied breeds was 5.26 in Duroc, 22.98 in Landrace, and 5.56% in Yorkshire pigs. The value in Landrace pigs was significantly (P < 0.001) higher than that in the other pigs. There was no significant difference between sexes. In general the heart of pigs with HCM was heavier, wider, longer, and thicker than that of clinically normal pigs. Backfat was the only growth trait with a difference (P < 0.05) among pig breeds. The HCM pigs were leaner than normal pigs. Leaner pigs may have a higher risk of HCM. Heritability of HCM was > 0.30 for all three breeds, but the standard errors of these estimates were high because of limited sample size, in particular for the Yorkshire and Duroc breeds. The preliminary results of this study indicate that HCM in pigs is moderately heritable; thus development of a high-HCM incidence line by selection is possible.

Animals↗

Echocardiographic assessment of spontaneously occurring feline hypertrophic cardiomyopathy. An animal model of human disease.

BACKGROUND: Necropsy studies in domestic cats have suggested the occurrence of a primary cardiac disease resembling hypertrophic cardiomyopathy (HCM) in humans. We used two-dimensional echocardiography to define morphological and functional features of HCM during life in 46 domestic cats evaluated in a subspecialty veterinary clinic. Cats were 8 months to 14 years old (mean, 6 years). METHODS AND RESULTS: During the follow-up period of as long as 49 months, 18 cats died (or were euthanatized) due to congestive heart failure, peripheral embolization, or both, and 3 other cats experienced out-of-hospital sudden, unexpected death. Echocardiography showed a small left ventricular cavity, associated with a variety of patterns of hypertrophy. Wall thickening was most often diffuse (involving ventricular septum and free wall) in 31 cats (67%) and segmental in 15 (33%), including 12 with thickening confined to anterior septum; wall thickening was judged to be asymmetrical in 42 and symmetrical (concentric) in 4. In 30 cats (65%), marked mitral valve systolic anterior motion produced dynamic obstruction to left ventricular outflow (Doppler estimated gradients, 25 to 110 mm Hg). Compared with survivors, cats with HCM that died with heart failure had greater left ventricular thickness (8.1 +/- 1.5 versus 7.3 +/- 0.9 mm; P < .05) and larger left atria (20.1 +/- 4.6 versus 16.8 +/- 3.4 mm; P = .01) and more often had the nonobstructive form (89% versus 48%; P < .01). CONCLUSIONS: A spontaneously occurring disease of domestic cats was identified by echocardiography and was similar in its phenotypic expression to HCM in humans; it was characterized by unexplained left ventricular hypertrophy in a variety of patterns with or without evidence of outflow obstruction. Unfavorable prognosis was associated with greater magnitude of hypertrophy and absence of outflow obstruction. Feline HCM may prove to be a valuable animal model of the human disease.

Animals↗

Applications of electroporation of adherent cells in situ, on a partly conductive slide.

Nontraumatic, simple, and reproducible procedures for the introduction of nonpermeant molecules into adherent mammalian cells by in situ electroporation are described. Cells are grown on a glass slide, half of which is coated with electrically conductive, optically transparent, indium-tin oxide. An electric pulse is applied in the presence of the molecules to be introduced, and their effect on the cellular phenotype can be observed. The cells growing on the nonconductive side of the slide do not receive any pulse and serve as controls. Careful adjustment of electric field strength can achieve the introduction of the molecules into essentially 100% of the cells, and this treatment causes no detectable disruption to cellular metabolism. This is applied in the presence of the fluorescent dye, Lucifer yellow, causing its penetration into the cells growing on the conductive half of the slide. The migration of the dye to the nonelectroporated cells growing on the nonconductive area is microscopically observed under fluorescence illumination.

Animals↗

Transition mutations in the 23S rRNA of erythromycin-resistant isolates of Mycoplasma pneumoniae.

Erythromycin is the drug of choice for treatment of Mycoplasma pneumoniae infections due to its susceptibility to low levels of this antibiotic. After exposure of susceptible strains to erythromycin in vitro and in vivo, mutants resistant to erythromycin and other macrolides were isolated. Their phenotypes have been characterized, but the genetic basis for resistance has never been determined. We isolated two resistant mutants (M129-ER1 and M129-ER2) by growing M. pneumoniae M129 on agar containing different amounts of erythromycin. In broth dilution tests both strains displayed resistance to high levels of several macrolide-lincosamide-streptogramin B (MLS) antibiotics. In binding studies, ribosomes isolated from the resistant strains exhibited significantly lower affinity for [14C]erythromycin than did ribosomes from the M129 parent strain. Sequencing of DNA amplified from the region of the 2S rRNA gene encoding domain V revealed an A-to-G transition in the central loop at position 2063 of M129-ER1 and a similar A-to-G transition at position 2064 in M129-ER2. Transitions at homologous locations in the 23S rRNA from other organisms have been shown to result in resistance to MLS antibiotics. Thus, MLS-like resistance can occur in M. pneumoniae as the result of point mutations in the 23S rRNA gene which reduce the affinity of these antibiotics for the ribosome. Since they involve only single-base changes, development of resistance to erythromycin in vivo by these mechanisms could be relatively frequent event.

Anti-Bacterial Agents↗

Electroporation of peptides into adherent cells in situ.

To study the effect of protein interactions in vivo upon cellular functions,such complexes may be disrupted through the introduction of peptides corresponding to the proteins' points of contact. In this communication a simple, rapid and reproducible procedure for peptide introduction into adherent cells by electroporation is described. Cells are grown on electrically conductive, optically transparent indium-tin oxide at the time of pulse delivery. Several electrode and slide configurations, necessary to obtain non-electroporated cells adjacent to the electroporated ones as a control, are outlined. Careful control of electric field strength achieved the introduction of the peptide into essentially 100% of the cells while this treatment caused no detectable disruption of their division cycle.

3T3 Cells↗

Unusual kinetics of uracil formation in single and double-stranded DNA by deamination of cytosine in cyclobutane pyrimidine dimers.

Mutagenesis studies have indicated that the deamination of cytosine in UV-induced cyclobutane pyrimidine dimers is a key part of an error-free process that can account for most of the C-->T base specificity that frequently characterizes UV-induced mutagenesis. The kinetics of deamination, as inferred from the mutagenic effect of delayed photoreactivation, is remarkable in its resemblance to a step function. To study the kinetics from a different point of view, we used an enzymatic approach combining photolyase and uracil-N-glycosylase treatment to detect the formation of uracil in UV-irradiated single or double-stranded infectious DNA of phage S13. Formation of abasic sites by removal of uracil was inferred from loss of infectivity. It is concluded that no uracil appeared at 37 degrees C within 20 minutes (single-stranded DNA) or 40 minutes (double-stranded DNA) after irradiation, but following those latent periods, most of the uracil residues rapidly appeared within a brief 14 minute period centered at 29 minutes (single-stranded DNA) and 55 minutes (double-stranded DNA) after irradiation. The timing appears to fully confirm the previous evidence that dimer cytosines in DNA deaminate with step-function-like kinetics. Furthermore, the appearance of uracil was shown to be dependent on the UV-induction of cyclobutane dimers containing cytosine.

Apurinic Acid↗

Comparison of morphologic findings in spontaneously occurring hypertrophic cardiomyopathy in humans, cats and dogs.

Morphologic features of spontaneously occurring hypertrophic cardiomyopathy (HC) were compared in 38 humans, 51 cats and 10 dogs. Asymmetric hypertrophy of the ventricular septum, marked disorganization of cardiac muscle cells, abnormal intramural coronary arteries and myocardial fibrosis were each present in the ventricular septum of human, feline, and canine forms of HC; these abnormalities were generally more severe and most frequently identified in humans. Asymmetric left ventricular hypertrophy (based on the calculated septal-to-free wall thickness ratio) was most common in humans (31 of 38 [81%]) and dogs (8 of 10 [80%]), as compared with cats (16 of 51 [31%]; p < 0.001) with HC; in all 3 species, hypertrophy was often diffuse, involving substantial portions of the anterolateral and posterior free walls, and the ventricular septum. Marked septal disorganization (> or = 5% of the tissue section) was present in 35 patients (92%), but in only 14 cats (27%) and 2 dogs (20%) (p < 0.001). Abnormal intramural coronary arteries occurred with similar frequency in the ventricular septum of patients (n = 25; 66%), cats (n = 38; 74%) and dogs (n = 6; 60%) (p < NS). Moderate-to-severe septal fibrosis was identified more commonly in humans (15 of 38 [39%]) than in animals (13 of 61 [21%]; p < 0.001). In all 3 species, abnormal intramural coronary arteries were most commonly observed within or at the margins of areas of fibrous tissue. These morphologic findings describe spontaneously occurring models of HC in cats and dogs with substantial structural similarities to the well-recognized disease entity in humans.

Adolescent↗

Case report 805: Synovial sarcoma, epithelial hyperplasia in the humeral air sacs, and formation of medullary bone.

In summary, we have reported a most interesting case of synovial sarcoma, epithelial hyperplasia in the air sacs, and formation of medullary bone in the left humerus of a 5-year-old female white pigeon. The tumor showed aggressive features radiologically and caused dysfunction of the left wing. The histologic findings and immunohistochemical reactions in this report were identical in many respects to the manifestation of synovial sarcoma described in human beings and dogs. Formation of medullary bone in female birds during the reproductive phase and hyperplasia of epithelia in the air sacs were also discussed.

Air Sacs↗

recA mutations that reduce the constitutive coprotease activity of the RecA1202(Prtc) protein: possible involvement of interfilament association in proteolytic and recombination activities.

Twenty-eight recA mutants, isolated after spontaneous mutagenesis generated by the combined action of RecA1202(Prtc) and UmuDC proteins, were characterized and sequenced. The mutations are intragenic suppressors of the recA1202 allele and were detected by the reduced coprotease activity of the gene product. Twenty distinct mutation sites were found, among which two mutations, recA1620 (V-275-->D) and recA1631 (I-284-->N), were mapped in the C-terminal portion of the interfilament contact region (IFCR) in the RecA crystal. An interaction of this region with the part of the IFCR in which the recA1202 mutation (Q-184-->K) is mapped could occur only intermolecularly. Thus, altered IFCR and the likely resulting change in interfilament association appear to be important aspects of the formation of a constitutively active RecA coprotease. This observation is consistent with the filament-bundle theory (R. M. Story, I. T. Weber, and T. A. Steitz, Nature (London) 335:318-325, 1992). Furthermore, we found that among the 20 suppressor mutations, 3 missense mutations that lead to recombination-defective (Rec-) phenotypes also mapped in the IFCR, suggesting that the IFCR, with its putative function in interfilament association, is required for the recombinase activity of RecA. We propose that RecA-DNA complexes may form bundles analogous to the RecA bundles (lacking DNA) described by Story et al. and that these RecA-DNA bundles play a role in homologous recombination.

Amino Acid Sequence↗

Clinical, echocardiographic, and Doppler imaging characteristics of mitral valve stenosis in two dogs.

Mitral stenosis was diagnosed noninvasively by echocardiography and Doppler imaging in 2 Bull Terriers. Two-dimensional echocardiography revealed severe atrial and moderate left ventricular dilatation; severely reduced mitral valve opening excursion; doming of the cranial mitral valve leaflet into the left ventricle during diastole; thickened, nodular cranial mitral valve leaflets; and reduced mitral valve orifice. M-mode echocardiographic findings additionally indicated greatly diminished mitral valve E to F slope and abnormal caudal mitral valve leaflet motion. Color flow Doppler imaging revealed bright bursts of color with aliasing originating from the stenotic mitral valve orifice, extending into the left atrium during systole, and into the left atrium during diastole. Spectral Doppler recordings revealed transvalvular mitral valve gradients and prolonged pressure half-times. Necropsy performed on 1 dog revealed extremely thickened, nodular, and stiff mitral valves with short, thickened, and fused chordae tendineae. The diagnosis of mitral valve stenosis was easily facilitated with diagnostic ultrasonography.

Animals↗