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Biomedical subjects

S K Liu

Publications and source records attributed to S K Liu.

At least 55 records · Page 3Linked to original sources

Mechanism of SOS mutagenesis of UV-irradiated DNA: mostly error-free processing of deaminated cytosine.

We measured the kinetics of growth and mutagenesis of UV-irradiated DNA of phages S13 and lambda that were undergoing SOS repair; the kinetics strongly suggest that most of SOS mutagenesis arises from the deamination of cytosine in cyclobutane pyrimidine dimers, producing C----T transitions. This occurs because the SOS mechanism bypasses T--T dimers promptly, while bypass of cytosine-containing dimers is delayed long enough for deamination to occur. The mutations are thus primarily the product of a faithful mechanism of lesion bypass by a DNA polymerase and are not, as had been generally thought, the product of an error-prone mechanism. All of these observations are explained by the A-rule, which is that adenine nucleotides are inserted noninstructionally opposite DNA lesions.

Cytosine↗

Tumor necrosis factor-alpha in human milk.

We previously demonstrated that certain biologic activities in human milk were partially blocked by antibodies directed against human tumor necrosis factor-alpha (TNF-alpha). In this study, immunochemical methods were used to verify the presence of TNF-alpha in human milk obtained during the first few days of lactation. Gel filtration revealed the presence of TNF-alpha by RIA in molecular weight fractions between 80 and 195 kD. TNF-alpha could not be detected consistently by conventional Western blotting or cytotoxic assays. Although immunoreactive bands were detected by a Western blot-125I protein A technique in TNF-alpha-positive fractions from gel filtration, those bands proved to be nonspecific. TNF-alpha in milk was reliably quantified by the competitive RIA. Those studies revealed that the concentrations of TNF-alpha in milk were 620 +/- 183 pg/mL. Although RNA to TNF-alpha was detected in milk leukocytes by Northern blotting, little TNF-alpha was found in those cells before or after stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine or 4 beta-phorbol-12 beta-myristate-13 alpha-acetate. The origin of this cytokine in human milk remains unclear. Nevertheless, this study suggests that TNF-alpha is present in early human milk in sufficient quantities to exert possible biologic effects upon the mammary gland of the mother or the immune system of the infant.

Adolescent↗

Case report 673: Telangiectic osteogenic sarcoma.

A case is presented of a telangiectatic osteogenic sarcoma involving the left third metatarsal of a 4-year-old male Great Dane dog. Radiographs revealed a diaphyseal, expanding, lytic lesion with minimal intralesional sclerosis and a sclerotic rim in the proximal portion. The lesion contained a large amount of blood. The biopsy specimens consisted of spaces which were outlined by fibrous osteoid or granulation tissue. There were islands of multinuclear giant cells and/or fibrous osteoid tissue. A diagnosis of aneurysmal bone cyst was made. The lesion was treated by curettage and insertion of cancellous bone graft but was progressive 10 weeks after treatment. The lesion was further curetted, and these biopsy specimens consisted of aneurysmally dilated spaces and areas of anaplastic sarcomatous cells with mitotic figures and osteoid production, characteristic of telangiectatic osteogenic sarcoma. The dog was euthanized as the owner requested; an autopsy was not performed.

Animals↗

Excision and transposition of Tn5 as an SOS activity in Escherichia coli.

Excision and transposition of the Tn5 element in Escherichia coli ordinarily appear to occur by recA-independent mechanisms. However, recA(Prtc) genes, which encode RecA proteins that are constitutively activated to the protease state, greatly enhanced excision and transposition; both events appeared to occur concomitantly and without destruction of the donor DNA. The recombinase function of the RecA protein was not required. Transposition was accompanied by partial, and occasionally full, restoration of the functional integrity of the gene vacated by the excised Tn5. The stimulation of transposition was inhibited by an uncleavable LexA protein and was strongly enhanced by an additional role of the RecA(Prtc) protein besides its mediation of LexA cleavage. To account for the enhanced transposition, we suggest that (i) there may be a LexA binding site within the promoter for the IS50 transposase, (ii) activated RecA may cleave the IS50 transposition inhibitor, and (iii) the transposase may be formed by RecA cleavage of a precursor molecule.

Bacterial Proteins↗

Effects of intracarotid and intravenous infusion of human TNF and LT on established intracerebral rat gliomas.

The effects of recombinant human tumor necrosis factor (TNF) and lymphotoxin (LT) were investigated against two different established rat gliomas. Single preestablished intracarotid (ic) or intravenous (iv) doses (1.5-2.0 x 10(6) units) were administered to Wistar rats with intracerebral C6 gliomas and Fischer 344 rats with intracerebral T9 gliomas. Five days after cytokine treatment, animals were sacrificed and tumor size determined by histopathologic techniques. In Wister rats, ic TNF produced a greater reduction in size of C6 tumors than iv TNF. Experiments with Fischer rats showed that both TNF and LT were more effective when administered ic compared to iv. Furthermore, LT induced a greater reduction in tumor size than TNF. Additional studies on the age-related susceptibility of these gliomas revealed early, 8-day tumors were more sensitive to ic LT than advanced, 14-day tumors. No direct toxicity of these cytokines against the tumor cells was detected in vitro indicating their autitumor effect was mediated by alternate mechanisms in vivo. Thus for regionally confined gliomas ic therapy was superior to iv therapy and LT was more effective than TNF. Cytokine treatment was most effective on earlier tumors and there appeared to be differences in efficacy related to the tumor-host combination.

Animals↗

Error-prone SOS repair can be error-free.

Most of the mutagenesis that accompanies the SOS repair of ultraviolet light-induced lesions in the single-stranded DNA of phage S13 is eliminated when the groES or the groEL gene of Escherichia coli is defective. Therefore, this SOS mutagenesis is not a necessary consequence of what is commonly called error-prone repair, but is additionally imposed on the repair system by the GroE heat shock proteins, which are responsible for the assembly of polypeptides into multimeric structures.

Bacterial Proteins↗

Mutagenesis by proximity to the recA gene of Escherichia coli.

Escherichia coli recA (Prtc) strains, which produce protease constitutive RecA proteins in the absence of DNA-damaging treatments, display an increased frequency of spontaneous mutations. These mutations occurred preferentially in the neighborhood of the recA gene. This cis-like mutagenic effect was observed in the recA, rexAB, phoE and bio genes. The localized mutagenesis can be explained by the ease with which RecA(Prtc) proteins are activated to the protease state, which implies that there should be a relatively high concentration of activated RecA protein near the recA gene, where the protein is synthesized. The unusually high frequency of mutation in the recA gene is a novel example of an overactive gene preferentially turning itself down by mutation.

Chromosome Mapping↗

Graves' ophthalmopathy. Correlation of saccadic eye movements with age, presence of optic neuropathy, and extraocular muscle volume.

Quantitative infrared oculography was used to record saccadic eye movements of 49 patients with Graves' ophthalmopathy. Peak saccadic velocities were decreased in those patients who developed or presented with optic neuropathy. This effect was more pronounced for larger eye movements. Peak saccadic velocity also decreased as total extraocular muscle volume and limitation of ocular motility increased. For any given extraocular muscle volume, peak saccadic velocity was 40 degrees/s slower in patients 40 years or older than in younger patients. The relationship between velocity and motility limitation was most pronounced for intermediate muscle volumes (8% to 15% of total orbital volume). Saccadic velocities in those patients with optic nerve compression often improved following treatment. This study demonstrated that eye movement recording was a useful adjunct in evaluation of patients with Graves' ophthalmopathy. Furthermore, age-related lowering of peak saccadic velocities implicated changes of extraocular muscle structure as a factor in the development of optic neuropathy.

Adolescent↗

Case report 622. Multiple cartilaginous exostoses.

The case is presented of multiple cartilaginous exostoses involving the right and left metatarsals and phalanges, left scapula, ends of several distal ribs, and the spinous processes of several thoracic and lumbar vertebrae in a 3-month-old female Scottish terrier dog. Radiographical studies showed circumscribed expansile lesions in the affected bones. The dog developed neurological deficits 3 weeks later. Myelography displayed extradural compression of the opaque column at several thoracolumbar vertebrae. The biopsy specimen from an affected phalanx consisted of trabecular bone and hemopoietic tissue covered by a thin cap of hyaline cartilage. The dog was euthanized due to the poor prognosis. At autopsy, the surface of the affected bones was covered by a bluish-white, smooth, undulating cartilage cap. Histopathologically, the cartilaginous cap consisted of hyaline cartilage without a reserve zone, and abnormal endochondral ossification. The hereditary nature and the malignant transformation of multiple cartilaginous exostoses in the dog have been considered.

Animals↗

groE genes affect SOS repair in Escherichia coli.

Repair of UV-irradiated bacteriophage in Escherichia coli by Weigle reactivation requires functional recA+ and umuD+C+ genes. When the cells were UV irradiated, the groE heat shock gene products, GroES and GroEL, were needed for at least 50% of the Weigle reactivation of the single-stranded DNA phage S13. Because of repression of the umuDC and recA genes, Weigle reactivation is normally blocked by the lexA3(Ind-) mutation (which creates a noncleavable LexA protein), but it was restored by a combination of a high-copy-number umuD+C+ plasmid and a UV dose that increases groE expression. Maximal reactivation was achieved by elevated amounts of the Umu proteins, which was accomplished in part by UV-induced expression of the groE genes. By increasing the number of copies of the umuD+C+ genes, up to 50% of the normal amount of reactivation of S13 was achieved in an unirradiated recA+ host.

Coliphages↗

Infrared oculography of Duane's retraction syndrome (type 1).

Eye movements of two patients with Duane's retraction syndrome (type 1) were recorded using high-resolution infrared oculography. Slowed hypometric abduction was found. The dynamics of adducting saccades in the affected hypometric eye were normal, suggesting an absence of functional cocontraction of the medial and lateral rectus muscles. Therefore, narrowing of the palpebral tissue on adduction most likely reflects a reorganization of the central ocular motor pathways.

Adult↗

Acute mitral regurgitation with papillary muscle rupture in a dog.

Papillary muscle rupture is uncommon in the dog. Two-dimensional echocardiography provides a rapid, noninvasive test in the diagnosis of acute, severe mitral regurgitation resulting from papillary muscle rupture. This report illustrates the usefulness of echocardiography to determine the cause of acute mitral regurgitation.

Acute Disease↗

Nine-month evaluation of dogs after open-heart surgical removal of heartworms.

Adult heartworms were surgically removed from 4 infected dogs by use of intracardiac techniques during cardiopulmonary bypass. The number of worms removed ranged from 12 to 14 per dog. Observation for 9 months after surgery gave no clinical evidence of active adult heartworm infection, in spite of the consistent finding of circulating microfilariae during the follow-up period. There were no significant early or late postoperative complications. Results of postoperative hematologic and biochemical studies were unremarkable. At necropsy (following euthanasia, 9 months after surgery) the heart and pulmonary arteries of all dogs were free of adult heartworms; pathologic changes attributable to residual infection were not found.

Animals↗

Clinical and pathologic findings in dogs with atherosclerosis: 21 cases (1970-1983).

Atherosclerosis was diagnosed on necropsy in 21 dogs in a 14-year period. Nine dogs died and 12 were euthanatized because of complications associated with the disease. The mean age was 8.5 +/- 0.5 years; 18 dogs were male. Three breeds (Miniature Schnauzer, Doberman Pinscher, and Labrador Retriever) had a higher prevalence of the disease than other breeds in the canine necropsy population of The Animal Medical Center. Most common clinical signs were lethargy, anorexia, weakness, dyspnea, collapse, and vomiting. Hypercholesterolemia, lipidemia, and hypothyroidism were common in affected dogs tested, and protein electrophoresis revealed high values for alpha 2 and beta fractions in all dogs tested. Electrocardiography indicated conduction abnormalities and myocardial infarction in 3 of 7 dogs. Necropsy revealed that affected arteries (including coronary, myocardial, renal, carotid, thyroidal, intestinal, pancreatic, splenic, gastric, prostatic, cerebral, and mesenteric) were yellow-white, thick and nodular, and had narrow lumens. Myocardial fibrosis and infarction also were observed in the myocardium. Histologically, affected arterial walls contained foamy cells or vacuoles, cystic spaces, mineralized material, debris with or without eroded intima, and degenerated muscle cells.

Animals↗

Osteosarcoma of the patella in a dog.

Osteosarcoma of the patella was diagnosed by biopsy in a 9-year-old, male dog of mixed breeding. The dog was originally examined because of intermittent lameness of the left hindlimb; there were minimal palpable abnormalities of the stifle. After the diagnosis, the owner refused further treatment for the dog. The dog was reexamined 13 months later because of a marked swelling of the stifle. The dog was euthanatized and necropsy findings confirmed the diagnosis.

Animals↗

Myocarditis and cardiomyopathy in the dog and cat.

Myocarditis and cardiomyopathy were diagnosed in 36 dogs from 11 litters, and myoendocarditis and restrictive cardiomyopathy were diagnosed in 51 cats. Most of the dogs and cats died unexpectedly. Spontaneous parvoviral infection in the dogs caused acute (myocytolysis with presence of intranuclear inclusion bodies in the myocytes), subacute (inflammatory reaction and myocytolysis), and chronic (fibrosis and myocytolysis) myocarditis, which led to extensive myocardial fibrosis and abnormality of the myocytes, similar to dilated cardiomyopathy in man. Spontaneous acute, subacute, and chronic myoendocarditis in the cats led to granulation, extensive fibrosis, and necrosis of the myoendocardium, i.e., like restrictive cardiomyopathy which occurs in man without eosinophilia. Thus, the dog and cat are important animal models of primary myocardial disease.

Acute Disease↗