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Biomedical subjects

K Kim

Publications and source records attributed to K Kim.

At least 361 records · Page 20Linked to original sources
PubMed1996

Primary stent implantation without coumadin in acute myocardial infarction.

OBJECTIVES: We tested the feasibility and efficacy of primary stent implantation without Coumadin in 74 patients within 8 h of the onset of acute myocardial infarction. BACKGROUND: Although stent implantation in patients with effort angina provides better short- and long-term outcomes than balloon angioplasty, it is not clear whether primary stent implantation is applicable or effective in acute myocardial infarction. METHODS: Primary sent implantation was attempted when 1) the lesion was not located distally in the main coronary branches, 2) the coronary artery did not show any severe calcification or excessive bending proximal to the lesion on fluoroscopy, and 3) the arterial diameter was > or = 2.5 mm. The results (group S) were compared with those of primary balloon angioplasty (group P). Poststenting regimens contained ticlopidine and aspirin without Coumadin. Poststenting inflation was performed with > or = 12 atm. RESULTS: Stent implantation was successful in 72 patients. Stent thrombosis was noted in only one patient who was not given ticlopidine, aspirin or Coumadin. The rates of restenosis and frequency of major clinical events during the hospital period in groups S and P were 0% versus 13.2% (p = 0.007) and 2.8% versus 18.6% (p = 0.009), respectively. Kaplan-Meier analysis demonstrated that cumulative 90-day clinical event-free rates in groups P and S were 98.1 +/- 16.0% versus 79.4 +/- 43.7% (p = 0.0068), and that 180-day rates were 86.5 +/- 38.4% versus 64.2 +/- 49.7% (p = 0.014). CONCLUSIONS: Primary stent implantation can improve clinical outcomes of patients with acute myocardial infarction when the stent is dilated adequately and antiplatelet drugs are used.

Angioplasty, Balloon, Coronary↗
PubMed1996

Amplification of stromelysin-3 transcripts from carcinomas of the colon.

Stromelysin-3 has been recently described in association with the stroma of different types of cancer including colorectal carcinomas. This article reports the detection of transcripts for stromelysin-3 (matrix metalloproteinase-11 [MMP-11]) in extracts of tissue from colorectal carcinomas using the technique of reverse transcription-polymerase chain reaction (RT-PCR). In 12 cases of primary colon carcinoma, stromelysin-3 messenger RNA (mRNA) was detected after 25 cycles, whereas this procedure did not reveal stromelysin-3 mRNA expression in one rectal carcinoma micrometastasis to the liver or in normal colon tissue (controls) after 30 cycles of PCR. However, stromelysin-3 mRNA was detected in normal colon specimens after 45 cycles. The high sensitivity of this technique allows application for the investigation of the expression of stromelysin-3 in small amounts of tissue.

Adenocarcinoma↗
PubMed1996

Yeast thiol-dependent protector protein expression enhances the resistance of Escherichia coli to hydrogen peroxide.

A soluble protein from Saccharomyces cerevisiae specifically provides protection against a thiol-containing oxidation system but not against an oxidation system without thiol. This 25-kDa protein was thus named thiol-dependent protector protein (TPP). The role of TPP in the cellular defense against oxidative stress was investigated in Escherichia coli containing an expression vector with a yeast genomic DNA fragment that encodes TPP (strain YP) and mutants in which the catalytically essential amino acid cysteine (Cys-47) has been replaced with alanine (strain YPC47A) or tryptophan (Trp-82) has been replaced with phenylalanine (strain YPW82F) by a site directed mutagenesis. There was a distinct difference between these three strains in regards to growth inhibition kinetics, viability, modulation of activities of superoxide dismutase and catalase, and the accumulation of oxidized proteins. These results suggest that TPP may play a direct role in the cellular defense against oxidative stress by functioning as an antioxidant protein.

Alanine↗
PubMed1996

Phase II study of topotecan in patients with extensive-stage small-cell carcinoma of the lung: an Eastern Cooperative Oncology Group Trial.

PURPOSE: To determine the response rate and survival of chemotherapy-naive patients with extensive-stage small-cell lung cancer (SCLC) treated with topotecan, and to determine the relationship of topotecan pharmacokinetics with response and toxicity. PATIENTS AND METHODS: Forty-eight patients with previously untreated, extensive-stage SCLC received 2.0 mg/m2 of topotecan daily for 5 days. The first 13 patients were treated without colony-stimulating factor (CSF) support; the next 35 patients received 5 micrograms/kg of granulocyte-colony-stimulating factor (G-CSF) for 10 to 14 days starting on day 6. Cycles were repeated every 3 weeks for a maximum of four cycles. Patients who had a partial response to topotecan after four cycles, stable disease after two cycles, or progressive disease at any time received salvage chemotherapy with cisplatin and etoposide. Topotecan pharmacokinetics were measured using a four-point sampling scheme. RESULTS: Of 48 patients, none had a complete response and 19 had a partial response, for an objective response rate of 39% (95% confidence interval [CI], 25.2% to 53.0%). The median response duration was 4.8 months (95% CI, 3.0 to 7.3). After a median follow-up duration of 18.2 months, the overall median survival time was 10.0 months (95% CI, 8.2 to 12.7); the 1-year survival rate was 39% (95% CI, 25.2% to 53.0%). Eight of 34 patients (24%) who received salvage chemotherapy responded. Four of 17 patients who did not respond to first-line therapy with topotecan responded to cisplatin and etoposide. The most common toxicity was hematologic. Ninety-two percent of patients treated without G-CSF developed grade 3 or 4 neutropenia, compared with 29% who received G-CSF. However, the incidence of neutropenic fevers was similar between the two groups (8% and 11%, respectively), and one patient in each group died of neutropenic fevers. There were no differences in objective tumor response, duration of response, time to treatment failure, or survival between the 13 patients who entered the study before G-CSF administration was mandated and the 35 patients who entered after and received G-CSF. There was poor correlation between the WBC count and absolute neutrophil counts (ANCs) and both the area under the curve (AUC) and maximum concentration++ (Cmx) of total topotecan in plasma. There was no correlation between the tumor response and either AUC or Cmx of total topotecan. CONCLUSION: The activity of topotecan in extensive-stage SCLC noted in this study warrants further investigation of this agent in phase III clinical trials.

Adult↗
PubMed1996

Expression of gamma-aminobutyric acid and gonadotropin-releasing hormone during neuronal migration through the olfactory system.

Neurons containing the decapeptide GnRH originate in the olfactory placodes and migrate into the central nervous system during fetal development. The neurotransmitter gamma-aminobutyric acid (GABA) has been proposed as a trophic factor and may also influence neuronal migration. Immunocytochemical analyses were conducted in fetal rats, mice, and humans to identify potential developmental relationships between cells containing GABA, and GnRH neurons. Cells containing GABA were found along the nasal portion of the GnRH migration pathway in rats, mice, and humans during development. A peak number of cells containing immunoreactive GABA was observed in the nasal compartment of rats at embryonic day 15. At this time (E15), a majority of GnRH neurons were clustered in the region of the cribriform plate. By postnatal day 1, all GnRH neurons had migrated into the CNS and GABA cells were virtually absent from the nasal compartment. Double-label and confocal analyses of GABA and GnRH in mice and rats demonstrated that some olfactory GABAergic neurons coexpress GnRH. This implies that neurons that transiently express GABA originate in olfactory placodes and migrate into the forebrain. Based on the transient dual-label and adjacent relationships between GABA and GnRH containing cells in the nasal compartment, and other data showing migrational and trophic roles for GABA in development, we suggest that GABA may directly influence GnRH neuronal migration and development.

Animals↗
PubMed1996

Hepatocyte growth factor is involved in the morphogenesis of tooth germ in murine molars.

The patterns of gene expression for hepatocyte growth factor (HGF) and its receptor, c-Met, were revealed in the tooth germ of rat mandibular molars using RT-PCR. In situ hybridization demonstrated that the HGF gene was expressed only in the cells of the dental papilla of the tooth germ in vivo. The characteristic temporospatial distribution of HGF and c-Met during germ development was revealed using immunohistochemical studies in vivo. In order to demonstrate the functional role played by HGF in tooth development, HGF translation arrest by antisense phosphorothioate oligodeoxynucleotide (ODN) was carried out in vitro. In the control experiment, explants of tooth germs from embryonic 14 day mice were cultured in a modification of Trowell's system under serum-free and chemically defined conditions for two weeks. Other explants were cultured with 15mer antisense or sense ODN targeted to the HGF mRNA. Both the control and the sense-treated explants showed normal histological structure, as observed in vivo. On the other hand, antisense-treated explants exhibited an abnormal structure in which the enamel organs were surrounded by a thin layer of dentin and dental papilla, appearing 'inside-out' compared to the control and sense-treated explants, although the cytodifferentiation of ameloblasts and odontoblasts was not inhibited. The explants treated with recombinant human HGF combined with antisense ODN showed normal development, indicating that exogenous HGF rescued the explants from the abnormal structure caused by antisense ODN. The findings of a BrdU incorporation experiment suggested that the imbalance between the proliferation activity of the inner enamel epithelium and that of the dental papilla caused by HGF translation arrest results in the abnormal structure of the tooth germ. These results indicate that HGF is involved in the morphogenesis of the murine molar.

Animals↗
PubMed1996

Progesterone together with estradiol promotes luteinizing hormone beta-subunit mRNA stability in rat pituitary cells cultured in vitro.

The present study examined the role of ovarian steroids, estradiol and/or progesterone in the regulation of luteinizing hormone beta-subunit (LH-beta) mRNA levels and LH release in the rat anterior pituitary cells cultured in vitro. When estradiol (10 nmol/l) and/or progesterone (100 nmol/l) were added to the cultures, neither estradiol or progesterone nor both together altered the basal LH-beta mRNA levels or LH release. Continuous exposure to gonadotropin-releasing hormone (GnRH, 0.2 nmol/l) for 24 h markedly induced LH-beta mRNA accumulation, and in this experimental condition, progesterone alone and progesterone + estradiol further augmented GnRH-induced LH-beta mRNA levels and LH release. Then we explored further the possibility that ovarian steroids are involved in modulating LH-beta mRNA stability in cultured rat pituitary cells where transcription was inhibited by actinomycin D. Anterior pituitary cells were preincubated with GnRH (0.2 nmol/l) for 16 h and, after removing GnRH from culture medium, the cells were incubated further in the presence of actinomycin D (5 mumol/l) for 24 h. The LH-beta mRNA levels gradually declined to about 30% of the control values (zero time point after GnRH removal) in a time-dependent manner. During this period, either progesterone alone or progesterone + estradiol clearly blocked the degradation of LH-beta mRNA species. These results indicate that ovarian steroids promote LH-beta mRNA stability, thereby contributing to the maintenance of GnRH-stimulated LH-beta mRNA levels.

Animals↗
PubMed1996

The neurochemistry of the GnRH pulse generator.

We review the crucial role of the two neurotransmitters norepinephrine (NE) and GABA in eliciting GnRH pulse. NE acts via an alpha l-receptor mechanism and also GABA acts at the alpha-subtype of the GABA receptor. The function of NE appears to be induction of phasic activation of GnRH neurons and GABA inhibits GnRH neurons tonically until they are all ready for phasic activation. By an unknown mechanism preoptic GABA release in dramatically reduced which causes simultaneous desinhibition of the GnRH neurons. Hence they release their product into the portal vessels simultaneously which is the appropriate signal for the pituitary ganodotrophs. The action of norepinephrine and GABA is most likely exerted at the perikarya level of the GnRH neurons since the alpha l-adreno receptor blocker doxazosin and GABA inhibit GnRH secretion only when applied into the medial preoptic/anterior hypothalamic area (where in the rat brain the GnRH perikarya are located). Utilizing a quantitative reverse transcription polymerase chain reaction, we demonstrate furthermore that GnRH receptors are present in the mediobasal hypothalamus as well as in the preoptic area of rats. Their function appears to serve autoinhibitory purposes since Buserelin added to medium significantly decreased GnRH release. Simultaneously, the release of GABA was increased and that of glutamate decreased. We conclude from these experiments that GABAergic and glutamatergic neurons in the hypothalamus may also be GnRH-receptive.

Animals↗
PubMed1996

Computed tomography: an unreliable indicator of pancreatic trauma.

Computed tomography (CT) is currently the modality of choice in evaluating pancreatic injury in patients suffering abdominal trauma who do not require immediate exploration. The purpose of this study was to determine the reliability of initial CT scanning in the detection of pancreatic trauma. A retrospective review was performed of all patients admitted to two Level 1 trauma centers over a 10-year period. Those patients identified with pancreatic injury who underwent initial evaluation with CT scanning were reviewed for clinical course and comparison of CT results with findings at laparotomy. Seventy-two patients of 16,188 admissions (0.4%) were identified with pancreatic injury. Mechanism of injury was blunt in 27 (37%), gunshot wound in 32 (45%), and stab wound in 13 (18%). There were 18 (25%) grade I, 32 (45%) grade II, 16 (22%) grade III, and 5 (7%) grade IV pancreatic injuries. Seventeen of the 72 patients with pancreatic injury underwent initial abdominal CT. The pancreas was normal on CT in 9 and of these, 8 underwent exploration, most commonly secondary to splenic injury. Three were found to have grade I pancreatic injury, two grade II, and three grade III, which required distal pancreatectomy. The pancreas was abnormal on CT in eight patients, and of these three underwent exploration. One patient had an injury upgraded from II on CT to III at exploration and underwent distal pancreatectomy. The mean pancreatic injury by CT was 0.45 versus 2.0 on exploration (P < 0.001). Injury to the pancreas following blunt trauma is rare. Computed tomography will often miss or underestimate pancreatic injuries that require operative treatment, and normal findings on initial scan should not be relied upon to exclude significant pancreatic trauma.

Abdominal Injuries↗
PubMed1996

Characterization and cell distribution of polycystin, the product of autosomal dominant polycystic kidney disease gene 1.

BACKGROUND: In a majority of cases, autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations within a putative open reading frame of the PKD1 gene. The encoded protein, polycystin, is predicted to span the plasma membrane several times and contains extracellular domains, suggestive of a role in cell adhesion. The cellular distribution and function of polycystin is not known. MATERIALS AND METHODS: We selected as immunogens two conserved 15 amino acid peptides: P1, located in a predicted extracellular region of polycystin, and P2, located in the C-terminal putative cytoplasmic tail. The anti-peptide antibodies from immunized rabbits were affinity purified on peptide-coupled resins and their specificity confirmed by their selective binding to recombinant polycystin fusion proteins. Western blotting and immunohistochemistry were used to characterize the size, tissue, and cell distribution of polycystin. RESULTS: A high-molecular mass protein (about 642 kD) was detected by Western blotting in rat brain tissue. A few additional bands, in the 100- to 400-kD range, probably representing tissue-specific variants and/or proteolytic fragments, were recognized in human and rat tissues. Polycystin was abundantly expressed in fetal kidney epithelia, where it displayed basolateral and apical membrane distribution in epithelial cells of the ureteric buds, collecting ducts, and glomeruli. In normal human adult kidney, polycystin was detected at moderate levels and in a cell surface-associated distribution in cortical collecting ducts and glomerular visceral epithelium. Expression of polycystin was significantly increased in cyst-lining epithelium in ADPKD kidneys, but was primarily intracellular. CONCLUSIONS: Polycystin appears to be a developmentally regulated and membrane-associated glycoprotein. Its intracellular localization in the cyst-lining epithelium of ADPKD kidneys suggests an abnormality in protein sorting in this disease.

Animals↗
PubMed1996

Detection of genomic alterations in human cervical cancer by two-dimensional gel electrophoresis.

Two-dimensional gel electrophoresis was used to comprehensively scan the whole genome of 6 cervical intraepithelial neoplasia (CIN) lesions, 7 cervical squamous cell carcinomas, 1 cervical adenosquamous cell carcinoma, and 2 cervical adenocarcinomas for multiple genetic alterations, such as DNA amplification, chromosome deletion, loss of heterozygosity, and chromosome translocation, as compared with the paired normal tissues. DNA spot analysis of the genomic 2-dimensional gels was performed by a computer color overlay system and by spot recognition software allowing for objective spot comparison and quantitation. Nine spots were found to be amplified in the cervical carcinomas while two amplified spots were detected in the CIN III lesions. Fourteen DNA spots were either reduced in their intensity or absent in cervical carcinomas as compared to their normal paired tissues. Reduction of intensity in 6 spots was observed in the 5 CIN III lesions. These genetic alterations may represent changes in cancer genes that are associated with human cervical carcinogenesis. Further characterization of these alterations may be significant to the understanding of cervical tumorigenesis and to the development of biomarkers for clinical trials in cancer chemoprevention.

Adenocarcinoma↗
PubMed1996

DNA quantification in cervical intraepithelial neoplasia thick tissue sections by confocal laser scanning microscopy.

Image analysis of tissue biopsies for determination of DNA content as an early marker of neoplasia is hampered by the complexity of corrections necessary to dea with nuclear truncation and overlap in thin sections. The use of confocal laser scanning microscopy (CLSM) for measurement of cellular DNA content on whole cells within thick tissue sections offers the advantage of preservation of cellular architecture, capacity for 3-dimensional analysis, and absence of sectioning artifacts. We have applied this technique to pararosaniline-Feulgen stained human cervical tissues graded from normal to cervical intraepithelial neoplasia (CIN) III. For the purpose of comparison, 15 microns sections were stained and mapped so that the same cell population could be analyzed by both integrated optical density and fluorescence intensity. Distribution of DNA content from normal cervical epithelial cells 2-3 layers out from the basal cell layer measured by both methodologies showed a stable G0/G1 population with no observable S-phase or G2 cells. Cells measured from areas of increasing CIN grade showed progressively higher DNA content values that were not observable in normal tissue. Although these data are preliminary they suggest that CLSM can be used to identify aneuploid states within defined structural areas of pre-invasive neoplasia.

Coloring Agents↗
PubMed1995

Mutational analysis of the att DNA-binding domain of phage Mu transposase.

The transposase (A protein) of phage Mu encodes binding to two families of DNA sites, att sites located at the Mu ends and enhancer sites located internally. Separate subdomains in the N-terminal domain I of Mu A protein are known to be involved in recognition of the att and enhancer sites. We have delineated an approximately 135 aa region within domain I beta gamma that specifies binding to Mu att sites. This peptide was overexpressed and its properties compared with that of the larger domain I beta gamma as well as the intact Mu A protein. Extensive mutagenesis of residues around a putative helix-turn-helix DNA-binding motif within the I beta domain identified several mutants defective in DNA transposition in vivo. Of these, Mu A(K157Q) was completely defective in att DNA-binding. Mu A(F131S) and Mu A(R146N) had a lower affinity for att DNA and low levels of transposition in vitro. Our results indicate that residues in the gamma region are required for activity and that residues outside the beta gamma region must also influence discrimination between the multiple att sites.

Amino Acid Sequence↗
PubMed1995

Excision of deoxyribose phosphate residues by DNA polymerase beta during DNA repair.

Eukaryotic DNA polymerase beta (pol beta) can catalyze DNA synthesis during base excision DNA repair. It is shown here that pol beta also catalyzes release of 5'-terminal deoxyribose phosphate (dRP) residues from incised apurinic-apyrimidinic sites, which are common intermediate products in base excision repair. The catalytic domain for this activity resides within an amino-terminal 8-kilodalton fragment of pol beta, which comprises a distinct structural domain of the enzyme. Magnesium is required for the release of dRP from double-stranded DNA but not from a single-stranded oligonucleotide. Analysis of the released products indicates that the excision reaction occurs by beta-elimination rather than hydrolysis.

Animals↗
PubMed1995

Detection of p21ras mutations in colorectal adenomas and carcinomas by enzyme-linked immunosorbent assay.

BACKGROUND: Point mutations of the ras protooncogene, primarily within codons 12 and 13, are commonly identified in colorectal carcinomas and large adenomas. Despite data suggesting that ras genotyping may have clinical significance with respect to colorectal cancer screening and prognosis, more widespread use has been limited because of the lack of a suitable assay system. The principal objective of this study was to assess the feasibility and validity of a qualitative enzyme-linked immunosorbent assay (ELISA) for detecting the four most common ras mutations in human colorectal tumors at the protein (p21ras) level. METHODS: Tissue homogenates (11-121 micrograms) from endoscopically or surgically resected colorectal adenomas, carcinomas, and normal mucosae were evaluated by a commercially available ELISA (Oncogene Science, Inc. Cambridge, MA) for mutant p21ras containing arginine position 12 (arg12), valine position 12 (val12), aspartate position 12 (asp12), and aspartate position 13 (asp13) amino acid substitutions. Portions of the same tissue from an initial series of 27 specimens also were subjected to mutant-enriched polymerase chain reaction (PCR) and/or PCR amplification with subsequent DNA sequence analysis to validate the ELISA data. RESULTS: Forty-seven adenomas, 9 carcinomas, and 14 normal mucosae were assayed. Mutations were identified in 16 (34%) of the adenomas (7-asp12, 7-val12, 2-asp13), 3 (33%) of the carcinomas (1-asp12, 1-arg12, 1-asp13), and none of the normal mucosae by ELISA: Polymerase Chain Reaction and DNA sequencing analyses demonstrated identical results for 21 of the 23 (91%) and 14 of 16 (88%) homogenates tested, respectively. The ELISA demonstrated an overall sensitivity of 80-86%, specificity of 90-92%, positive predictive value of 86-100%, and negative predictive value of 86-91%. CONCLUSIONS: The ELISA is a feasible and valid approach for identifying p21ras mutations in human colorectal adenomas and carcinomas.

Adenoma↗