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Biomedical subjects

J G Kim

Publications and source records attributed to J G Kim.

At least 163 records · Page 9Linked to original sources

Selectivity of oxomemazine for the M1 muscarinic receptors.

The binding characteristics of pirenzepine and oxomemazine to muscarinic receptor were studied to evaluate the selectivity of oxomemazine for the muscarinic receptor subtypes in rat cerebral microsomes. Equilibrium dissociation constant (KD) of (-)-[3H]quinuclidinyl benzilate([3H]QNB) determined from saturation isotherms was 64 pM. Analysis of the pirenzepine inhibition curve of [3H]QNB binding to cerebral microsome indicated the presence of two receptor subtypes with high (Ki = 16 nM, M1 receptor) and low (Ki = 400 nM, M3 receptor) affinity for pirenzepine. Oxomemazine also identified two receptor subtypes with about 20-fold difference in the affinity for high (Ki = 84 nM, OH receptor) and low (Ki = 1.65 microM, OL receptor) affinity sites. The percentage populations of M1 and M3 receptors to the total receptors were 61:39, and those of OH and OL receptors 39:61, respectively. Both pirenzepine and oxomemazine increased the KD value for [3H]QNB without affecting the binding site concentrations and Hill coefficient for the [3H]QNB binding. Oxomemazine had a 10-fold higher affinity at M1 receptors than at M3 receptors, and pirenzepine a 8-fold higher affinity at OH receptors than at OL receptors. Analysis of the shallow competition binding curves of oxomemazine for M1 receptors and pirenzepine for OL receptors yielded that 69% of M1 receptors were of OH receptors and the remaining 31% of OL receptors, and that 29% of OL receptors were of M1 receptors and 71% of M3 receptors. However, M3 for oxomemazine and OH for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could be classified as a selective drug for M1 receptors and also demonstrate that rat cerebral microsomes contain three different subtypes of M1, M3 and the other site which is different from M1, M2 and M3 receptors.

Animals↗

Rudimentary polydactyly.

A case of rudimentary polydactyly on the radial aspect of the thumb of a 4-year-old male was examined. Histologic examination revealed hyperkeratosis and acanthosis in the epidermis and large numbers of nerve bundles in the dermis. With immunoperoxidase staining for S-100 protein, the nerve corpuscles were positively stained. We think that rudimentary polydactyly is a kind of congenital traumatic neuroma and that the possible cause may be intrauterine amputation.

Child, Preschool↗

Jejunal inflammatory fibroid polyp presenting as intussusception--a case report with review of the literature.

A 52-year-old woman was presented with intermittent abdominal pain and vomiting for 10 days. Abdominal CT scan disclosed a dilated small bowel loop with a round solid mass in the right anterior supravesical space. The clinical impression was intussusception caused by small bowel tumor. She underwent an exploratory laparotomy. The macroscopic and microscopic findings confirmed an inflammatory fibroid polyp of jejunum causing intussusception. To the best of our knowledge, this was the 5th reported case of such a presentation in English medical literature.

Female↗

Helicobacter pylori infection and development of gastric or duodenal ulcer in arthritic patients receiving chronic NSAID therapy. The Misoprostol Study Group.

OBJECTIVES: Helicobacter pylori infection and nonsteroidal anti-inflammatory drug use are both common causes of peptic ulcer. It remains unclear whether H. pylori/NSAID interactions occur, and if they do, with what result(s). METHODS: We prospectively evaluated development of gastric or duodenal ulcers in 181 arthritics followed for up to 3 months while receiving an NSAID chronically and with no active anti-ulcer medications. H. pylori status was determined with a sensitive, specific ELISA for anti-H. pylori IgG. RESULTS: H. pylori infection was present in 51%; peptic ulcers developed in 24. H. pylori infection was present in only 36% of those who developed a duodenal ulcer. Stepwise logistic regression analysis indicated none of the variable factors of age, gender, alcohol consumption, type of arthritis, or H. pylori status were significantly associated with development of peptic ulceration. CONCLUSIONS: These data suggest that H. pylori does not confer increased risk of ulceration in arthritics receiving NSAIDs chronically.

Adult↗

Mammalian heterogeneous ribonucleoprotein A1 and its constituent domains. Nucleic acid interaction, structural stability and self-association.

With a view toward further understanding the structure-function relationships of the eukaryotic heterogeneous ribonucleoprotein (hnRNP) A1, and in particular its multiplicity of nucleic acid-interactive domains, we have studied the nucleic acid binding properties of the globular N-domain (UP1) and sequence-repetitive, flexible C-domain, the thermal denaturation of UP1 and the concomitant effects of binding polynucleotide, and the self-associative properties of the full-length protein. Utilizing protein tryptophan fluorescence as a probe, polynucleotide binding was shown to stabilize UP1 against thermal unfolding. The denaturation profile of UP1-poly(thymidylic acid) complexes was biphasic, suggesting that unfolding of the two subdomains of UP1 can occur independently. This is in agreement with a previously proposed structure in which only one of the two UP1 subdomains binds the nucleic acid. The subdomains of UP1 can be prepared by controlled proteolysis of A1, further indicating that these two globular segments within A1 are connected by an exposed, flexible linkage. Circular dichroism measurements on UP1 confirm previous data that this portion of A1 binds single-stranded nucleic acids non-co-operatively. UP1 clearly shows a preference for single-stranded nucleic acids with a 2'-OH, since its affinity for poly(U) is three times higher than for poly(dU), and five times higher than its affinity for poly(2'-OCH3U). The nucleic acid-interactive properties of the C-domain were further examined by preparing a synthetic peptide polymer (M(r) approximately 12,000) containing about seven repeats of a 16-residue sequence, GNFGGGRGGNYGGSRG, which in turn comprises two copies of the C-terminal consensus, GN(F/Y)GG(G/S)RG. The polymer of this sequence exhibited significant affinity for the fluorescent polyribonucleotide, poly(ethenoadenylic acid), binding stoichiometrically at < or = 0.2 M-Na+. Complex formation was accompanied by an increase in aggregate formation, as indicated by the appearance of scattering. For purposes of comparison, the data were analyzed via the linear co-operative model of McGhee and von Hippel, though this model may not be fully descriptive of the protein-nucleic acid complex(es) formed in this case. In contrast to the non-co-operative binding mode of the UP1 domain, the C-polymer exhibited moderate co-operativity, comparable to that seen with full-length A1. Although addition of sufficient NaCl reversed the interaction, a sigmoidal binding isotherm could still be observed (with sufficient added polymer) at 0.8 M-NaCl. This suggests that non-electrostatic interactions contribute significantly to the free energy of binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Identification of cis-regulatory elements in the myelin proteolipid protein (PLP) gene.

Regulatory elements of the proteolipid protein (PLP) gene were identified physically by footprinting and gel mobility shift assays and functionally by transfecting glial cell lines with PLP-chloramphenicol acetyltransferase chimeric genes. In both human and rat glial cells, only several hundred base pairs of upstream sequence were sufficient for high level activity of the human PLP promoter. This region contains five sites that contact nuclear proteins in vitro. More distal recognition sites may exist, as regions upstream of -524 displayed silencing activity indicative of a negative regulatory element. A series of site directed mutations revealed one essential positive element (ATGGA at -118) which is found in other genes encoding myelin proteins. Our combined biochemical and functional analyses indicate that the key cis sites for maximal tissue-specific expression of PLP in cultured glial cells are clustered near the promoter. Within this cluster are several conserved motifs that may coordinate the regulation of myelin-specific genes.

Animals↗

Papillomavirus found in anorectal squamous carcinoma, not in colon adenocarcinoma.

We used polymerase chain reaction DNA amplification methods for the detection and typing of genital human papillomaviruses in paraffin-embedded tissue sections of five patients with anorectal squamous cell carcinoma and 22 patients with colonic adenocarcinoma. The cases were further tested by in situ hybridization with biotin-labeled probes specific for human papillomavirus types 6/11, 16/18, and 31/33/35. By polymerase chain reaction, human papillomavirus DNA was demonstrated in all of the cases of anorectal squamous cell carcinoma and in none of the cases of colonic adenocarcinoma for which analyzable DNA was available. Tumor cell nuclei stained for human papillomavirus DNA by in situ hybridization in four of the five cases of squamous cell carcinoma and in none of the cases of colonic adenocarcinoma. We conclude that human papillomavirus types usually associated with malignant transformation are uniformly present in anorectal squamous cell carcinoma but are absent from adenocarcinoma of the colon.

Adenocarcinoma↗

Induction of vesicle-to-micelle transition by bile salts for DOPE vesicles incorporating immunoglobulin G.

The vesicle-to-micelle transition of immunoliposomes formed by dioleoylphosphatidyl-ethanolamine (DOPE) and palmitoyl-immunoglobulin G (p-IgG) was investigated in the presence of bile salts and conjugated bile salts. Turbidity and the release of calcein from liposomes were measured as a function of the amount of bile salts added and compared with the solubilizing profiles of the salts according to the number and configurational state of hydroxy groups in the cholate. The solubilizing phenomena by bile salts conjugated with glycine or taurine were investigated in comparison with non-conjugated bile salts. The solubilizing effect of bile salts on the bilayer of immunoliposomes increased remarkably with the number of hydroxy groups, but was not influenced by the configurational state of the hydroxy group. The half-maximal concentration of bile salts, defined as the concentration giving the half-maximum turbidity of liposome solutions, decreased with hydrophobicity in the phosphatidylcholine (PC) bilayer. The increase in the hydrophobicity of bile salts induces the ability to permeabilize and solubilize phospholipid vesicles. In the case of PC or PE liposome bilayers with inserted protein, bile salts conjugated with taurine or glycine had lower hydrophobicity than non-conjugated bile salts and showed a lower half-maximal concentration. The conjugated bile salts are believed to interact with lipids and solubilize the bilayers, while the head groups of bile salts interact with the inserted protein and extract it from the lipid bilayer.

Bile Acids and Salts↗

Novel member of the zinc finger superfamily: A C2-HC finger that recognizes a glia-specific gene.

A novel member of the zinc finger superfamily was cloned by virtue of its binding to cis-regulatory elements of a glia-specific gene, the myelin proteolipid protein (PLP) gene. Named MyTI (myelin transcription factor I), this gene is most highly transcribed in the developing nervous system, where expression precedes induction of its presumptive target, PLP. Low levels of MyTI transcripts can be detected in nonneural tissues only by polymerase chain reaction analysis. Zinc is a necessary cofactor for DNA binding of MyTI, as the zinc-chelating agent 1,10-orthophenanthroline eliminates binding activity. Zinc may stabilize the DNA-binding domain of MyTI by coordinating three cysteine and one histidine residue in a Cys-X5-Cys-X12-His-X4-Cys (C2-HC) arrangement. The MyTI protein has six fingers of the C2-HC class arranged in two widely separated clusters. These two domains of DNA binding can function independently and recognize the same DNA sequence, suggesting that MyTI may contribute to the higher-order structure of a target promoter by simultaneously binding both proximal and distal sites. The six fingers are highly conserved, suggesting that they arose from successive duplication events, while the linker regions diverge in size and sequence. Both amino acid sequence comparisons and secondary-structure predictions indicate that the C2-HC fingers of MyTI do not resemble the zinc-mediated loops of C2-H2 fingers, C2-C2 fingers, or Cx clusters. MyTI may therefore be the prototype of a new structural family of zinc-stabilized DNA binding proteins.

Amino Acid Sequence↗

Percutaneous mitral valvuloplasty in a mid-term pregnant woman with severe rheumatic mitral stenosis.

A 28-year-old woman with severe mitral stenosis underwent percutaneous mitral valvuloplasty at 26 weeks' gestation. Balloon dilation using a double 18-18 mm balloon resulted in improvement in mean mitral pressure gradient (32 to 8 mmHg) and in calculated mitral valve area (0.9 to 2.4 cm2) without complications and any evidence of fetal distress during procedures with an estimated radiation exposure to the fetus of 0.13 rem. This procedure resulted in the disappearance of symptoms of congestive heart failure and allowed for normal full term spontaneous delivery of a 3.51 Kg boy without any complication.

Adult↗

PDGF stimulation of inositol phospholipid hydrolysis requires PLC-gamma 1 phosphorylation on tyrosine residues 783 and 1254.

PDGF binding to its receptor promotes the association with and stimulates the phosphorylation of PLC-gamma 1 at tyrosine and serine residues. Also, PDGF induces an increase in the hydrolysis of inositol phospholipids by PLC. How PDGF activates PLC was investigated by substituting phenylalanine for tyrosine at PLC-gamma 1 phosphorylation sites 771, 783, and 1254 and expressing the mutant enzymes in NIH 3T3 cells. Phenylalanine substitution at Tyr-783 completely blocked the activation of PLC by PDGF, whereas mutation at Try-1254 inhibited and mutation at Tyr-771 enhanced the response. Like the wild type, PLC-gamma 1 substituted with phenylalanine at Tyr-783 became associated with the PDGF receptor and underwent phosphorylation at serine residues in response to PDGF. These results suggest that PLC-gamma 1 is the PLC isozyme that mediates PDGF-induced inositol phospholipid hydrolysis, that phosphorylation on Tyr-783 is essential for PLC-gamma 1 activation. These results provide direct evidence that growth factor receptors activate the function of intracellular protein by tyrosine phosphorylation.

Animals↗

A biotin-streptavidin enzyme immunoassay for detection of antibodies to porcine granulosa cell antigens.

A colorimetric solid-phase enzyme immunoassay has been developed which quantifies antibodies to porcine granulosa cell membrane antigens in rabbits immunized with porcine granulosa cells. A cell-free, particulate membrane preparation of porcine granulosa cells was used as coating antigen. A biotinylated second antibody in conjunction with a streptavidin-beta-galactosidase conjugate was utilized to amplify reactivity. The enzyme beta-galactosidase was used due to high background obtained using peroxidase, presumably due to endogenous peroxidase activity of the tissue. Sigmoidal serum dilution curves were obtained with immune rabbit sera indicating that absorbance was related to the concentration of antibodies. Assay activity was reduced by preincubation of immune serum with granulosa cell membranes. Sera from ovariectomized or pre-immune rabbits did not yield any specific binding in the assay. This assay has potential applicability for quantifying antiovarian and antigranulosa cell antibodies in women suspected of having autoimmune premature ovarian failure.

Animals↗

Vesicle to micelle transitions of egg phosphatidylcholine liposomes induced by nonionic surfactants, poly(oxyethylene) cetyl ethers.

Vesicle to micelle transitions of sonicated liposomes of egg yolk phosphatidylcholine (EPC) induced by a homologous series of nonionic surfactants, poly(oxyethylene) cetyl ethers [POE(n) cetyl ether], were investigated by using the method of turbidity titrations. The turbidities of the mixed dispersions of sonicated vesicles and surfactant were systematically measured as a function of the surfactant added for a wide range of lipid concentrations (from 0.51 to 6.35 mM EPC). From the titration curves, two threshold points representing onset and complete solubilization of liposomal membranes were determined as a probe for the effect of the length of ethylene oxide (EO) moiety on the phase behavior of ternary system of POE(n) cetyl ethers-EPC-excess water. Patterns of turbidity curves and the surfactant concentrations at two threshold points as well as widths of region between two transitions, where lamellar sheets and mixed micelles may coexist, mainly depended on the length of EO head group. With changing the lengths, solubilization of liposomes and phase diagram showed optimal behavior. That is, in the middle range of EO numbers, it resulted in narrowest coexistence region between onset and complete solubilization. Assuming the equilibrium partitioning model, critical effective molar ratios of surfactant to lipid, Rsat, free surfactant concentrations, Dw, and the partition coefficient of surfactant between bilayer and aqueous phase, K, in surfactant-saturated liposomes were quantitatively determined as a function of EO number. Effective ratios, Rsol, and free surfactant concentration in mixed micelles were also determined. In addition, the effects of CMC and HLB of surfactants on the solubilization of liposome were discussed.

Egg Yolk↗

Survival and cell acquisition rates after preimplantation embryo biopsy: use of two mechanical techniques and two mouse strains.

Two strains of mouse embryos at the four- and eight-cell stages had biopsy specimens obtained by means of two different mechanical techniques: aspiration and displacement. Embryos and biopsy specimen cells were evaluated for survival and development. Blastomere acquisition rates were significantly higher with the displacement biopsy technique; however, no difference in survival or developmental rates was found in blastomere biopsy specimens removed from either four-cell or eight-cell embryos. A maximum of one blastomere can be removed from a four-cell embryo, whereas three blastomeres can be taken at biopsy from an eight-cell mouse embryo without significantly affecting embryo development, although mouse strain differences were noted. Intact, viable, biopsied blastomeres will develop in vitro when cocultured with morphologically intact embryos. Births of live offspring after embryo biopsy are reported.

Animals↗

The efficacy of a combination administration of gonadotropin-releasing hormone agonist and gonadotropins for controlled ovarian hyperstimulation in IVF program.

In 105 patients with the past history of poor response to the previous controlled ovarian hyperstimulation (COH) due to poor follicular growth or premature LH surge, the efficacy of pituitary suppression with gonadotropin-releasing hormone agonist (GnRHa) in IVF/GIFT program was evaluated in 112 cycles of COH using a combination regimen of leuprolide acetate (Lupron) and FSH/hMG or pure FSH from May to December, 1989. After suppression phase, serum E2 and progesterone levels decreased significantly, but there was no change in serum LH and FSH levels. There was no occurrence of premature LH surge during COH. Eleven cycles (9.8%) were cancelled, and 3 cycles (3.0%) failed in the transvaginal oocytes retrieval. The 7.00 +/- 3.32 follicles (FD greater than or equal to 12 mm) were observed, and 6.11 +/- 4.15 oocytes were retrieved. The 3.59 +/- 2.57 oocytes were fertilized and cleaved with the cleavage rate of 55.7%. In 83 IVF patients, 4.08 +/- 2.39 embryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET of 19.3%. In 6 GIFT patients, 7.83 +/- 3.31 oocytes were available for transfer. When compared with the previous 108 cycles, the cancellation rate during COH was decreased and all the parameters of the outcome of COH including the pregnancy rate were increased. These data suggest that GnRHa therapy for pituitary suppression is an effective adjunct to the current gonadotropin regimens for COH in IVF/GIFT and can increase the probability of oocytes retrieval and pregnancy, especially in the previous poor responders.

Adult↗

Isolation and characterization of rat carcinoembryonic antigen.

A rat tumor-associated antigen with properties similar to those of human carcinoembryonic antigen (CEA) has been detected with rabbit immune sera in extracts of transplantable rat colonic adenocarcinoma, RCA-1. This antigen, termed rat CEA, was also detectable by a monkey antihuman CEA serum and a rat monoclonal antibody to rat CEA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of perchloric acid extracts of RCA-1 tumor, followed by immunoblotting with the above-mentioned anti-CEA reagents, revealed that rat CEA activity resided in components with a molecular weight of approximately 350 kD. The glycoprotein nature of these components was indicated by positive staining with periodic acid-Schiff. Sephadex G-200 chromatography, as well as Sepharose 4B chromatography with and without sodium dodecyl sulfate indicated that the 350-kD components existed in the extracts as molecular aggregates. The 350-kD material, which had been purified by an affinity column containing rat monoclonal antibodies to rat CEA, reacted with the rabbit and monkey anti-CEA sera. This provided strong evidence that serological activity of rat CEA was confined to the 350-kD components.

Animals↗

Factors affecting penetration of zona-free hamster ova.

The sperm penetration assay is an expensive, time-consuming test to assess male fertility in vitro. Although some investigators are enthusiastic in its application, others feel that it is not sensitive or specific enough to be used as part of the routine infertility evaluation. Indeed, this bioassay is not a faithful reproduction of in vivo conditions. However, if the SPA is abnormal, it is unlikely that sperm will fertilize a human ovum in vivo. Conversely, a normal SPA does not guarantee successful in vivo fertilization. No bioassay can be absolute in its predictive value, but false-negative results must be kept to a minimum for this bioassay to be of any clinical significance. Each laboratory performing the SPA should optimize the assay for sensitivity, reproducibility, and minimization of false-negative results and then establish normal and abnormal ranges of its own. If the limitations of the SPA are kept in mind, and if we employ it very selectively, it may still be useful.

Female↗

Liposarcoma arising in a giant lipomatous polyp of the esophagus.

A case of liposarcoma in a giant pedunculated lipoma of the esophagus in a 49-year-old Korean woman who presented intermittent swallowing difficulty for 3 years is reported. Endoscopy and esophagography revealed that a giant smooth longitudinal tumor mass almost entirely occupied the esophageal lumen. A total esohagectomy was done. The tumor was 20 cm in length and 7 cm in average diameter with an obvious stalk measuring 3 cm in length and 1 cm in diameter. Microscopic examination disclosed a lipoma with focal ulceration and liposarcomatous change infiltrating into interstitial fibrous tissue at its distal end.

Esophageal Neoplasms↗