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Biomedical subjects

S Chang

Publications and source records attributed to S Chang.

At least 379 records · Page 21Linked to original sources

Therapeutic ultrasound in the treatment of glaucoma. I. Experimental model.

Controlled ultrasonic energy was used to treat a series of laboratory animals in which glaucoma had been induced experimentally. Insonification successfully reduced elevated intraocular pressure in the majority (86%) of test animals. Histopathologic review of globes examined at varying time intervals following treatment showed localized thinning of the sclera with intact conjunctiva, allowing filtration and focal disruption of ciliary epithelium. This technique of treating elevated intraocular pressure in a noninvasive manner offers potential for clinical application in humans.

Animals↗

Shape change of sickled erythrocytes induced by pulsed rf electrical fields.

The shape change of sickled erythrocytes induced by electrical pulses was investigated under various experimental conditions using different suspending media. The purpose of this research is to find a set of conditions under which sickled erythrocytes from an individual with sickle cell anemia (SS erythrocytes) can be desickled with minimal damage to the membrane. Previously we observed, using 0.9% NaCl solution, that rounding of the SS erythrocytes eventually led to hemolysis even when the field was turned off. Using short pulses, we have now observed that the rounding of sickled erythrocytes does not necessarily lead to hemolysis if buffer solutions such as Hanks' solution are used. The cause of the shape change is believed to be the perforation of the erythrocyte membrane by the potential induced by applied fields. The field-induced membrane potential has been calculated for spherical cells and infinitely long cylinders. Using an ellipsoid of revolution as a model, we generalize the calculation of membrane potential. These calculations indicate that a transverse field is less effective in inducing a potential than a longitudinal field.

Anemia, Sickle Cell↗

Effect of hyperthermia on experimental choroidal melanoma.

Thirty-five rabbit eyes were implanted subchoroidally with Greene's hamster melanoma. When the tumours reached a base diameter of 5 mm, they were treated with ultrasonically induced hyperthermia with a range of temperatures and exposure durations (43-67 degrees C and 75 s to 60 min). Of the 23 treated eyes examined two months after treatment eight showed complete regression of the tumour. Seven showed initial tumour regression, but there was subsequent regrowth of tumour round the margins of the original mass. In eight eyes the tumour continued to grow, though in some cases the rate of growth appeared to be slower than in the controls. In contrast, in all untreated animals the tumour grew to fill the vitreous cavity. These preliminary findings indicate that ultrasonically induced hyperthermia can be an effective local treatment of this intraocular tumour model.

Animals↗

Efficacy of ECT: a meta-analysis.

The authors analyzed several rigorously controlled studies that compared the efficacy of ECT with that of simulated ECT, placebo, and antidepressants. The data from these studies were combined statistically (with the Mantel-Haenszel method for the combination of fourfold tables), showing ECT's clear superiority over all these other forms of treatment for severe depression. The authors similarly analyzed the data from several studies comparing the efficacy of unilateral nondominant ECT with that of bilateral ECT and found no significant difference in their efficacy.

Antidepressive Agents, Tricyclic↗

Reduction in plasma cholesterol and increase in biliary cholesterol by a diet rich in n-3 fatty acids in the rat.

Cholesterol and lipoprotein metabolism were investigated in a group of rats fed a fish oil-supplemented diet, a rich source of n-3 fatty acids. For comparison purposes, other groups of rats were fed either safflower oil (n-6 fatty acids) or coconut oil (saturated fatty acids). Diets were isocaloric and contained identical amounts of cholesterol. Rats fed fish oils for 2 weeks showed a 35% lower plasma cholesterol level than rats fed safflower oil, who in turn showed a 14% lower plasma cholesterol level than those fed coconut oil. The fall in plasma cholesterol level with fish oils was associated with significant falls in low density and high density lipoprotein cholesterol levels, but with no significant change in the ratio of low density to high density lipoprotein cholesterol. The fatty acid compositions of plasma, hepatic, and biliary lipids showed relative enrichment with n-3 fatty acids, reflecting the composition of the diet. The fish oil diet increased the basal secretion rate of cholesterol into bile, but the bile acid secretion rate remained unchanged. It is suggested that n-3 fatty acids reduce the plasma cholesterol level in rats by increasing the transfer of cholesterol into bile.

Animals↗

Modification and processing of Bacillus licheniformis prepenicillinase in Escherichia coli. Fate of mutant penicillinase lacking lipoprotein modification site.

We have previously shown that Bacillus licheniformis prepenicillinase is modified and processed to form membrane-bound penicillinase in Escherichia coli which contains N-acylglyceride-cysteine27 at the NH2 terminus. In the present study, we have constructed, by in vitro site-directed mutagenesis, two mutant penicillinase genes in which the modification site (the 27th cysteine residue in prepenicillinase) is either converted into serine (penPSer27) or is deleted along with the preceding four residues (Ala23 to Cys27, delta penP2327). The modification, processing, and subcellular localization of these two mutant penicillinases in E. coli cells were studied. Our results indicate that the delta penP2327 deletion mutant prepenicillinase is largely metabolically inert and the unmodified and uncleaved form is associated with the membrane fraction; a small fraction (about 7-9%) appears to contain glyceride-modified prepenicillinase (presumably at the Cys-21 position) which is not cleaved. In contrast, the Cys-27 in equilibrium Ser-27 point mutant prepenicillinase is processed into two forms which contain Asn-29 and Ser-35 at their NH2 termini, respectively, and the bulk of the processed penicillinase appears to be located in the peri-plasm. These results are discussed in terms of the substrate specificities of signal peptidases in E. coli.

Amino Acid Sequence↗

Perfluoropropane gas in the management of proliferative vitreoretinopathy.

Perfluoropropane (C3F8), an expanding fluorinated hydrocarbon gas, was used as an adjunct to vitreous surgery in the management of 18 patients with retinal detachment complicated by proliferative vitreoretinopathy. Ten patients had reattached retinas six months after disappearance of the gas. The average intraocular longevity of the gas in successful cases was 92 days; that in failed cases was 62.7 days. This difference was not statistically significant. However, internal retinal tamponade by longer-lasting gases appears to increase the rate of retinal reattachment in the surgical management of proliferative vitreoretinopathy.

Eye Diseases↗

Treatment of total retinal detachment in morning glory syndrome.

A 14-year-old girl had headaches and sudden loss of vision as a result of total retinal detachment in association with the morning glory optic nerve anomaly. Metrizamide cisternography with contrast dye introduced into the subarachnoid space disclosed migration of metrizamide with radiographic enhancement in the subretinal space. The demonstration of an abnormal communication between the subarachnoid and subretinal spaces suggested that the subretinal fluid is of cranial origin. The patient underwent surgical removal of a window of dura from the optic nerve sheath. This resulted in retinal reattachment and improvement of visual acuity to 20/200. The retina was still attached after a 15-month follow-up period.

Adolescent↗

Recombination following transformation of Escherichia coli by heteroduplex plasmid DNA molecules.

Circular heteroduplex DNA molecules introduced into Escherichia coli-competent cells are converted to new recombinant plasmids as a result of enzymatic actions in vivo. A pair of plasmids with partial sequence homology were each linearized at a different position with restriction enzymes, and the termini were made flush with the single-strand-specific S1 nuclease. Duplex molecules were then formed by melting and annealing these plasmid DNAs together. In contrast to linear homoduplex molecules, heteroduplexes circularize and therefore transform E. coli efficiently. Unique DNA sequences on each of the parental strands in the transforming heteroduplexes can be selectively incorporated or deleted as a result of in vivo enzymatic activities in transformed cells. This method permits the generation of new recombinant sequences in vivo without relying solely on the presence of convenient restriction sites for manipulation of DNA fragments in vitro.

DNA Restriction Enzymes↗

Nucleotide sequence of the Escherichia coli prolipoprotein signal peptidase (lsp) gene.

The nucleotide sequence of the prolipoprotein signal peptidase (lsp) gene has been determined. The lsp gene was found to be adjacent to the isoleucyl-tRNA synthetase ( ileS ) gene, such that the termination codon of the ileS gene overlaps with the initiation codon of lsp. These two genes are transcribed in the same direction and the major promotor for the lsp gene appears to be upstream of ileS . Identification of the lsp gene was established by amplification of prolipoprotein signal peptidase activity in strains carrying a subcloned 1.1-kilobase Stu I-Acc I fragment and was further confirmed by introducing mutational alterations in the COOH terminus of the protein that caused a decrease in prolipoprotein signal peptidase activity. The deduced amino acid sequence indicates that prolipoprotein signal peptidase contains 164 residues. Unlike most exported proteins, there is no apparent signal peptide sequence for the lsp protein. Computer-assisted secondary structure analysis of the deduced amino acid sequence identified four hydrophobic regions that share features common to transmembrane segments in integral membrane proteins.

Bacterial Outer Membrane Proteins↗

Scanning electron microscopic observations of the oocyst, sporoblast and sporozoite of Plasmodium yoelii yoelii.

Scanning electron microscopy was used to study the surface characteristics of the oocyst, sporoblast and sporozoite of Plasmodium yoelii yoelii. Observations were made of the sporogonic stages of 6-12 day infections of the malaria parasite in Anopheles stephensi. Oocyst and sporoblast development were not synchronous. The surface of the undifferentiated (early stage) oocyst appeared smooth, whereas that of differentiated (late stage) oocysts were rough or wrinkled. The wall of the differentiated oocysts showed numerous micropores at higher magnification (x15,000-20,000) the biological significance of which is not known. Small, bud-like satellite bodies were seen attached to some oocysts. Various forms of different stages of the sporoblast were described. Sporozoite budding took place on the surface of the sporoblast body. The sporozoite was elongate, curved and with a blunt anterior end.

Animals↗

Physiological and mutational protein variations in the ciliary membrane of Paramecium.

The proteins in the ciliary membrane of wild-type and mutant Paramecium tetraurelia are examined with SDS and IEF gels. Over 80% of the proteins in the ciliary membrane belong to two groups: the immobilization antigen (I-Ag), which is a 220-280 kD surface protein, and a set of at least four integral proteins slightly over 40 kD (the 40 k), most of which focus near pH 4.0 (the acidic 40 k). Variations of the I-Ag in its apparent molecular weight appear spontaneously in different clones of the same strain and can be triggered by changing the culture temperatures. We discovered that the members of the acidic 40 k family also vary in their relative proportion. Furthermore, the variations in I-Ag and those in acidic 40 k are tightly coupled. The concerted changes suggest a co-regulation in the synthesis of these proteins. The ciliary membranes of 20 mutants of 11 complementation groups known for their behavioral and electrophysiological defects are examined. Coupled variations of I-Ag and acidic 40 k among clones, similar to those of the wild type, are seen. Besides the I-Ag and the acidic 40 k, this membrane has over 60 other species of proteins, most of which are invariant. Shifts in the isoelectric points of two of these minor proteins have been correlated with two different mutations, 'fast-2' and 'paranoiac A'. No electrophoretic shifts can be correlated with the 'pawn B' mutation as found by Merkel et al. [35].

Animals↗

Selective groups of neuronal and mesodermal cells recognized early in grasshopper embryogenesis by a monoclonal antibody.

Our aim in generating monoclonal antibodies against the grasshopper nervous system is to identify molecules expressed early in neuronal development. A crude homogenate of the adult nervous system was used as the immunogen, and the hybridoma supernatants were screened on young grasshopper embryos. Here we report on the I-5 monoclonal antibody, which recognizes an antigen appearing in an interesting pattern of ectodermal and mesodermal cells early in the embryonic development of the grasshopper. Amongst the cells stained are the pioneer neurons in the central nervous system and the periphery, and the muscle pioneers.

Animals↗

Use of an intraocular gas tamponade to find retinal breaks.

We used the receding meniscus of an intraocular bubble being absorbed or the advancing meniscus of an expanding bubble to find the levels of retinal breaks in five patients with retinal detachments in which the breaks could not be found by the usual examination techniques. When we used a receding meniscus, the subretinal fluid was drained and the volume replaced by a perfluorocarbon gas calculated to fill the eye below the probable level of the retinal break. The bubble closed the break and maintained reattachment until the gas was absorbed. The level of the meniscus when redetachment first occurred indicated the level of the break. When we used an advancing meniscus, small amounts of perfluorocarbons were injected without drainage of subretinal fluid. As the gas bubble expanded it reattached the retina from above downward. When the bubble covered the retinal break, it tamponaded it and the remaining fluid absorbed within hours. The level of the meniscus when the retina became reattached marked the level of the retinal break.

Adult↗

The perfluorocarbon gases in the treatment of retinal detachment.

Four straight chain perfluorocarbon gases that had been studied in animals were tried in 30 patients. The larger volumes injected into patients made for extended disappearance times. Two milliliters of CF4 diminished to half volume in six days and had a total disappearance time of 16 days; 0.8 ml of C2F6 diminished to half volume in 10 days and had a disappearance time of 40 days; 1 ml of C3F8 diminished to half volume in 35 days and disappeared in 70 days; 0.6 ml of C4F10 diminished to half volume in 45 days and disappeared in 120 days. The expansion potential was estimated to be the same as measured in the animal model.

Animals↗

Human sympathetic ophthalmia. An analysis of the inflammatory infiltrate by hybridoma-monoclonal antibodies, immunochemistry, and correlative electron microscopy.

A case of human sympathetic ophthalmia, enucleated after surgical trauma, was studied by means of hybridoma-derived monoclonal antibodies, histochemistry, and transmission electron microscopy. The choroidal infiltrate was composed predominantly of T-lymphocytes of the suppressor/cytotoxic subset (OKT8+); only 5% of the cells were immunoglobulin-producing B-lymphocytes (kappa or lambda light chain positive), thereby explaining the well-known paucity of plasma cells in the infiltrate. The epithelioid cells and phagocytic histiocytes in the choroid were la+ and OKM1+, antigenic determinants specific for bone marrow-derived monocytes, and their cytoplasms exhibited histochemical reactivity for alpha-1-antichymotrypsin and lysozyme. Ultrastructurally, the choroidal epithelioid cells contained single melanin granules in the cytoplasm, but these were membrane-bound and frequently associated with lysosomal material, features militating against these cells being transformed choroidal melanocytes. By means of immunologic and ultrastructural analysis, the Dalen-Fuchs nodules were found to be composed of a mixture of histiocytes (la+ and OKM1+) and depigmented retinal pigment epithelial cells (la- and OKM1-); the latter cells focally formed desmosomes and displayed inclusions of lipofuscin. Scattered within the Dalen-Fuchs nodules were small numbers of T-lymphocytes of the suppressor/cytotoxic subset. We have concluded that the uveitis and retinal pigment epithelial changes are mediated by a T-cell, delayed hypersensitivity pathogenetic mechanism (cell-mediated immunity), possibly directed at surface membrane antigens that may be shared by photoreceptors, retinal pigment epithelial cells, and choroidal melanocytes.

Animals↗

Genetic and biochemical distinction among Chinese hamster cell emtA, emtB, and emtC mutants.

Genetic and biochemical experiments have enabled us to more clearly distinguish three genetic loci, emtA, emtB, and emtC, all of which can be altered to give rise to resistance to the protein synthesis inhibitor, emetine, in cultured Chinese hamster cells. Genetic experiments have demonstrated that, unlike the emtB locus, neither the emtA locus nor the emtC locus is linked to chromosome 2 in Chinese hamster cells, clearly distinguishing the latter two genes from emtB. emtA mutants can also be distinguished, biochemically, from emtB and emtC mutants based upon different degrees of cross-resistance to another inhibitor of protein synthesis, cryptopleurine. Two-dimensional gel electrophoretic analysis of ribosomal proteins failed to detect any electrophoretic alterations in ribosomal proteins from emtA or emtC mutants that could be correlated with emetine resistance. However, a distinct electrophoretic alteration in ribosomal protein S14 was observed in an emtB mutant. In addition, the parental Chinese hamster peritoneal cell line of an emtC mutant, and the emtC mutant itself, are apparently heterozygous for an electrophoretic alteration in ribosomal protein L9.

Alkaloids↗