Search PubMed⌕ Search

Biomedical subjects

K E Kim

Publications and source records attributed to K E Kim.

At least 37 records · Page 2Linked to original sources
PubMed1996

Intestinal distribution of human Na+/H+ exchanger isoforms NHE-1, NHE-2, and NHE-3 mRNA.

The identity of Na+/H+ exchanger (NHE) isoforms in the human small intestine and colon and their role in vectorial Na+ absorption are not known. The present studies were undertaken to examine the regional and vertical axis distribution of NHE-1, NHE-2, and NHE-3 mRNA in the human intestine. Ribonuclease protection assays were used to quantitate the levels of mRNA of these isoforms in various regions of the human intestine. In situ hybridization technique was used to localize NHE-2 and NHE-3 mRNA in the colon. The NHE-1 isoform message was present uniformly throughout the length of the human intestine. In contrast, mRNA levels for human NHE-2 and NHE-3 isoforms demonstrated significant regional differences. The NHE-3 abundance was found in decreasing order: ileum > jejunum > proximal colon = distal colon. The NHE-2 message level in the distal colon was significantly higher than in the proximal colon but was evenly distributed in the small intestine. In addition, NHE-2 mRNA was present in surface epithelial cells as well as in cells of the crypt region, suggesting the presence of NHE-2 message throughout the vertical axis of the colonic crypts. In contrast, NHE-3 mRNA was localized to surface colonocytes in the proximal colon. On the basis of this tissue-specific localization of NHE-2 and NHE-3 mRNA, it can be speculated that the relative contribution of NHE-2 and NHE-3 isoforms in Na+ absorption in the human intestine may be region specific, and these putative apical isoforms may be differentially regulated.

Amino Acid Sequence↗
PubMed1995

Reduced level of octamer binding transcription factor (Oct-1) is correlated with H2B histone gene repression during differentiation of HL-60 cells by all-trans retinoic acid.

To gain insight on the role of transacting factors in the regulatory mechanism of H2B histone gene expression during the differentiation of HL-60 cells by all-trans retinoic acid (retinoic acid), the binding pattern of the nuclear proteins to various elements in the human H2B histone upstream region has been investigated with DNase I footprinting and DNA mobility shift assay. The level of H2B histone mRNA was markedly reduced at 48 hr in retinoic acid-treated HL-60 cells. The H2B histone mRNA was repressed in proportion to the concentration of retinoic acid. In DNase I footprinting analysis, a nuclear factor (octamer binding transcription factor, Oct-1) bound at -42 bp (ATTTGCAT) both before and after retinoic-acid-induced differentiation of HL-60 cells. One DNA-protein complex was formed by DNA mobility shift assay, and the level of Oct-1 decreased during retinoic-acid-induced differentiation. In the cycloheximide-treated HL-60 cells, the level of Oct-1 also reduced. These results suggest that the transcriptional repression of H2B histone gene during retinoic-acid-induced differentiation in HL-60 cells may be mediated by reduced level of Oct-1.

Base Sequence↗
PubMed1995

Spatial analysis of Honolulu motor vehicle crashes: I. Spatial patterns.

This study describes spatial patterns in Honolulu motor vehicle accidents for 1990. A method for geo-coding accident locations is utilized with approximately 98% of the crash locations being identified. Spatial software tools are developed for describing the degree of spatial concentration. The spatial patterns of different types of accidents and accidents for every hour of the day, weekdays and weekends separately, are analyzed. Accidents spatially fluctuate dynamically, as a response to changing traffic patterns and volume. Generally, most accidents are closer to employment centers than to residential areas. In the suburban and rural areas, however, accidents are more likely to involve fatalities or serious injuries and be related to night-time driving and alcohol. It is shown that these conditions spatially correlate with single-vehicle crashes and crashes with opposite direction vehicles. The spatial patterns point to the limits of "blackspot" analysis.

Accidents, Traffic↗
PubMed1995

Spatial analysis of Honolulu motor vehicle crashes: II. Zonal generators.

The spatial relationship between activities which generate trips and motor vehicle accidents is examined and applied to the City and County of Honolulu for 1990. A method is described for examining spatial variations in motor vehicle accidents, aggregated into small geographical areas. A spatial lag model is developed which examines the zonal relationship of motor vehicle accidents to population, employment and road characteristics. The resulting model is tested for each hour of the day, weekdays and weekends separately. The predictors of accidents fluctuate according to different trip generating activities and change considerably over the day. The method can generate expected accidents, allowing for an identification of areas which have higher than expected levels. It is argued that this method focuses attention on characteristics of neighborhoods and areas, and not just on the road system.

Accidents, Traffic↗
PubMed1995

Daily fluctuations in honolulu motor vehicle accidents.

Changes in daily motor vehicle accidents during 1990 are examined for the City and County of Honolulu. Adjusting for changed reporting criteria, daily accidents fluctuate according to an interaction between traffic volume, weekday travel patterns, holidays and weather. Fridays, particularly, and Saturdays have more daily accidents. Minor holidays generate more daily accidents, but major holidays generate fewer daily accidents, primarily because of lower traffic volume. Rainfall increases the risk of accidents substantially. The interaction between afternoons and rainfall is particularly dangerous. Unemployment also appears to reduce daily accidents.

Accidents, Traffic↗
PubMed1995

A 33 kDa Pit-1-like protein binds to the distal region of the human thyrotrophin alpha-subunit gene.

Our previous studies demonstrated that at least two DNA regions with upstream limits between positions -223 to -190 and positions -151 to -135 of the human TSH gene are important for transcriptional regulation by TRH in GH3 rat pituitary cells. The proximal region (-151 to -135 bp) including the cAMP-responsive element (CRE) was required for the induction of the TSH gene by TRH, while the distal region (-223 to -190 bp) containing an element similar to the binding site for the pituitary-specific transcription factor, Pit-1, was necessary to amplify the effects of TRH. To determine whether a pituitary-specific nuclear protein, in addition to the CRE-binding protein, is involved in the molecular mechanism of TRH regulation, a gel retardation assay and Southwestern blot analysis were performed on the distal region with GH3 cell nuclear extracts. GH3 extracts generated a distinct DNA-protein complex that was effectively eliminated in the presence of excess unlabelled DNA fragment, and TRH treatment increased the affinity of protein binding remarkably. Excess Pit-1 DNA-binding sequence from the rat prolactin gene inhibited formation of the complex, but mutation of the Pit-1 consensus sequence in the distal region did not eliminate the complex. In addition, Southwestern experiments showed that a 33 kDa nuclear protein present in GH3 cells bound to this region and its binding affinity was increased slightly 2 h after TRH treatment, with the maximal increase (fivefold) at 3 h, which was similar to the results when using gel retardation. Phosphatase treatment of nuclear protein also resulted in a loss of binding affinity. Taken together, these data indicate that the interaction of a pituitary-specific nuclear protein, identical or closely related to Pit-1, with the distal region may be involved in the TRH stimulation of human TSH gene expression.

Animals↗
PubMed1994

Involvement of a cAMP-responsive DNA element in mediating TRH responsiveness of the human thyrotropin alpha-subunit gene.

TRH is known to stimulate the transcription of the TSH gene in pituitary cells. To examine TRH-responsive elements of the human TSH alpha-subunit gene, we have used transient transfection of GH3 rat pituitary tumor cells. Using this system, TRH treatment stimulated expression of a reporter gene containing 846 base pairs from the 5'-flanking region of the human glycoprotein hormone alpha-subunit gene linked to luciferase. Analysis of 5'-deletions of the alpha-subunit sequence revealed that at least two DNA regions with upstream limits between positions -223 to -190 and positions -151 to -135 are important for regulation by TRH. The more proximal region includes a previously defined cAMP-response element (CRE) while the more upstream region contains an element with sequence similarity to the binding site for the pituitary transcription factor, Pit-1. The TRH responsiveness of each individual region was tested by inserting fragments upstream of a thymidine kinase-luciferase reporter gene. The -151 to -100 region had basal enhancer activity and permitted a 3.4-fold response to TRH. The -223 to -168 region did not permit a TRH response, but possessed basal enhancer activity. The combination of both regions resulted in a 5-fold stimulation by TRH. To assess the contributions of different signal transduction pathways, various combinations of treatments were examined. Combined treatment with TRH and forskolin led to an additive activity. Treatment with TRH plus phorbol 12-myristate-13-acetate resulted in the same level of reporter gene activity as with either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The FSH beta-subunit promoter directs the expression of Herpes simplex virus type 1 thymidine kinase to the testis of transgenic mice.

The bovine FSH beta-subunit promoter (2.3 kb) was coupled to the coding sequence of the Herpes simplex virus type 1 thymidine kinase (HSV-tk) gene and introduced into mouse embryos. A full-length tk transcript was found in the pituitary and testis. In the testis an additional truncated version of tk mRNA was also expressed. Two sets of primer extension fragments were identified, one corresponding to transcription initiation at or near the cap site of the FSH-beta gene, the other to transcription initiation within the tk gene. Furthermore, the latter, shorter transcript contained a 227 bp deletion. Only the long transcript was translated into immunoreactive tk in the later stages of developing spermatids. The tk protein was also functional in the testes, since spermatogenesis was either arrested or the germinal epithelium almost completely destroyed in transgenic males treated with the antiherpetic agent. If the FSH-beta-HSV-tk transgene also functions correspondingly in the pituitary, these mice will provide a useful model for studies on FSH.

Animals↗
PubMed1992

Analysis of DNA sequences required for pituitary-specific expression of the glycoprotein hormone alpha-subunit gene.

Transient transfection studies have been used to determine the DNA sequences of the glycoprotein hormone alpha-subunit gene that are required for tissue-specific expression. In the initial phase of these studies, a variant mouse alpha gene was identified which contains a fully palindromic cAMP response element (CRE). The corresponding region of a previously cloned and sequenced mouse alpha gene contains a single point mutation that disrupts the symmetrical nature of this element. DNase footprint studies demonstrate that the fully palindromic CRE binds the CRE-binding protein with much higher affinity than the imperfect palindrome. Transfection experiments using both mouse alpha gene variants demonstrate differences in basal and cAMP-induced expression. Studies of the cAMP response of the human alpha gene indicated that this gene contains sequences other than the known CRE that are sufficient to permit a transcriptional response to cAMP in both placental and pituitary cells. Expression of human and mouse alpha-subunit genes has been examined in cells of the gonadotrope, thyrotrope, and trophoblast lineages to identify DNA sequences that mediate selective transcription of the alpha gene in these cells. The results demonstrate that sequences between about -500 and -200 are important for expression in the pituitary, but not the placenta. Clustered point mutations were used to further characterize sequences required for expression in the pituitary. Two regions, one at positions -445 to -438 and one at positions -337 to -330, were required for expression in cells of the gonadotrope lineage. One of these regions, at -337 to -330, is also important for expression in thyrotropes. When linked to a minimal promoter, multiple copies of the -344 to -300 region had transcriptional enhancer activity in gonadotropes and thyrotropes, but not in several other cell types. These results are consistent with a model involving different combinations of regulatory elements that determine cell-specific alpha expression in gonadotropes and thyrotropes.

Animals↗
PubMed1992

Characterization of a non-tissue-specific, 3',5'-cyclic adenosine monophosphate-responsive element in the proximal region of the rat prolactin gene.

The nature of a DNA element located in the -100 to -85 region of the rat PRL gene has been characterized. Previous studies demonstrated that this region may contribute to basal and hormonally regulated expression of the PRL gene. As this region contains a sequence with similarity to a consensus cAMP-responsive element (CRE), a possible role for the cAMP response element binding protein (CREB) has been explored. A point mutation which made the PRL CRE-like sequence less like a consensus CRE had little effect on basal or cAMP-stimulated expression of a PRL-luciferase reporter gene. DNase footprint studies demonstrated that the proximal region of the PRL gene does not contain a high affinity CREB binding site. Mobility shift experiments demonstrated that the major GH3 nuclear protein which interacts with the -100 to -85 region of the PRL gene in vitro is not CREB. Transfection of a dominant inhibitor of CREB action had little or no effect on expression of an indicator gene containing the PRL proximal region. Thus, the PRL proximal region does not contain a high affinity CREB binding site, and it is unlikely that CREB plays a major role in expression of the PRL gene. The functional capabilities of the -100 to -85 region of the PRL gene were then tested in a transfection assay. Synthetic multimers of this region were found to be sufficient to permit a transcriptional response to cAMP or TRH in GH3 cells and cAMP in Rat-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

RBC improved survival due to recombinant human erythropoietin explains effectiveness of less frequent, low dose subcutaneous therapy.

Effectiveness of less frequent, once weekly, low dose subcutaneous recombinant human erythropoietin (rHuEPO) in maintaining 35% hematocrit in patients with chronic renal failure, predialysis and ESRD receiving dialysis, is dependent on rHuEPO induced prolonged RBC survival. One year of weekly rHuEPO doses to 7 patients originally part of the National Cooperative Protocol were evaluated for a total of 372 weeks for an average of 53 weeks per patient. The original 8 to 12 week dosage was directed by protocol for units per dose at 3 doses per week (4 IV, 3 subcutaneous). Thereafter, all doses were subcutaneous. Units/dose and doses/week were titrated to keep hematocrit at 35-38%. Dosage reduction of rHuEPO was determined by two investigators at the time of each examination. Statistical correlation was performed on effect of rHuEPO on 51Cr T1/2 RBC survival changes and changes of rHuEPO weekly doses. Patients evaluated at specific time points in the study were compared to themselves as their own controls by paired t-test analysis. The long-term increased RBC count correlated with prolonged RBC survival by 51Cr T1/2 rather than reticulocytosis. A relatively increased ease of sustaining the target hematocrit of 35% was demonstrated from the 8th week to 1 year. Thirty-two percent of the expanded RBC mass was older at 12 weeks and 22% was older at 1 year. rHuEPO dosage was reduced to 27% at weeks 8-12, to 21% at weeks 20-24, and to 38% at 1 year corresponding to prolonged RBC survival. 51Cr T1/2 increased from 21.6 days control to 28.6 days at 12 weeks and 26.3 days at 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Decreased catalytic subunit mRNA levels and altered catalytic subunit mRNA structure in a cAMP-resistant Chinese hamster ovary cell line.

The mechanisms responsible for decreased levels of cAMP-dependent protein kinase activity in a mutant Chinese hamster ovary cell line have been examined. The cAMP-resistant Chinese hamster ovary 10260 cell line was found to possess only 20% of the cAMP-dependent protein kinase activity found in wild-type cells. The presence of decreased concentrations of the catalytic subunit in these cells was confirmed through binding studies using a radiolabeled, heat-stable inhibitor of the kinase. Cloned Chinese hamster ovary catalytic subunit cDNAs were isolated, characterized, and used as hybridization probes to examine the relative concentrations of catalytic subunit mRNAs in the wild-type and 10260 cell lines. A 40-50% decrease in the concentration of the mRNA for the C alpha isozyme of the catalytic subunit was observed in 10260 cells, as compared with wild-type. This decrease in catalytic subunit mRNA concentration probably accounts for a portion of the decreased kinase activity in the mutant cells. Further analysis of C alpha mRNA by polymerase chain reaction confirmed the decreased expression of C alpha mRNA in 10260 cells and further demonstrated the presence of two different species of C alpha mRNA in the 10260 cells. One species of C alpha cDNAs was indistinguishable from the wild-type cDNA, but the other species was shorter. Nucleotide sequence analysis of the amplified cDNAs led to the identification of a 191-base pair deletion in the shorter cDNA. Gene transfer studies using wild-type and 10260 C alpha cDNAs demonstrated that the longer cDNA from the 10260 cells produced wild-type activity, but the shorter cDNA was inactive. These studies suggest that at least two alterations in gene expression are responsible for decreased cAMP-dependent protein kinase activity in the 10260 cell line. One alteration results in an approximately 2-fold decrease in the concentrations of C alpha mRNA in the cells. The other change produces two species of C alpha mRNA; one of the C alpha mRNAs does not encode an active kinase.

Amino Acid Sequence↗
PubMed1991

Comparative clinical pharmacology of calcium channel blockers.

Calcium channel blockers are effective antihypertensive agents, both as initial monotherapy and in combination with other antihypertensive agents. These drugs are also effective in the treatment of chronic, stable angina, variant angina and supraventricular arrhythmias. Drugs in this class have different affinities for calcium channels in vascular smooth muscle, cardiac muscle, cardiac sinus and atrioventricular node. They are all useful in hypertension and angina, but only verapamil and diltiazem are also useful in the control of heart rate and supraventricular arrhythmias. Nimodipine may control vascular spasm following subarachnoid hemorrhage. Calcium channel blockers have also been used in the treatment of migraine headache and Raynaud's phenomenon.

Calcium Channel Blockers↗
PubMed1991

Cardiovascular hemodynamic effects of correction of anemia of chronic renal failure with recombinant-human erythropoietin.

The results of 8 to 12 weeks of treatment of the anemia of uremia with rHuEPO in patients with chronic renal failure and uremia are: a sustained increased hematocrit; increased RBC mass, and subsequent increased MAP; and increased TPRI. The observed trends of decreased LVEF, and echo Doppler evidence of a trend toward LV systolic and diastolic dysfunction, although not individually statistically significant, represent 3 separate evaluation techniques coupled with hypertension and TPRI increase during administration of rHuEPO to increase the hematocrit and packed red blood cell volume in patients with chronic renal failure and anemia. Increased TPRI and hypertension associated with correction of uremic anemia vasodilation and the increased blood viscosity have been noted in earlier investigations with transfusions. The hypertension and elevated TPRI demonstrated during rHuEPO therapy in patients with progressive chronic renal failure associated with increased hematocrit, and the trends toward systolic and diastolic cardiac dysfunction are noted herein. These changes were associated with the combined increase of packed RBC mass and plasma volume in this study. The natural progressive course of worsening of renal function exhibited by these patients could have limited their ability to regulate plasma volume, making them vulnerable to volume-dependent hypertension and a significant preload adding to potential cardiac dysfunction in addition to the increased TPRI.

Anemia↗
PubMed1990

DNA sequences required for expression of the LH beta promoter in primary cultures of rat pituitary cells.

To begin analysis of the DNA sequences necessary for luteinizing hormone (LH) gene transcription, fusion genes containing the 5' flanking region of the rat LH beta or the human alpha-subunit gene linked to luciferase were transfected into primary cultures of rat pituitary cells. The LH beta-luciferase construct was expressed in the primary cultures at a level 50 times greater than a promoterless luciferase control plasmid. Little or no expression of the LH beta-luciferase construct was detected following transfection of MCF-7, JAR or GH3 tumor cell lines. Treatment of transfected cells with gonadotropin-releasing hormone resulted in a modest induction of LH beta-luciferase activity. Considerably higher levels of LH beta-luciferase activity were obtained with cultures from ovariectomized rats than were obtained with cultures from intact female rats. Analysis of 5' deletions of the LH beta-luciferase construct demonstrated that activity was well maintained even after substantial deletions. The shortest construct, which contained 75 base pairs of 5' flanking sequence had 38% of the activity of the longest which contained 1.7 kilobase pairs of flanking sequence. These findings demonstrate that transfection of primary cultures of rat pituitary cells may provide a useful system for analysis of the cis-acting sequences and trans-acting factors required for LH gene expression.

Animals↗
PubMed1990

Male breast cancer--a 20-year review of 16 cases at Yonsei University.

Sixteen cases of male breast cancer seen over a 20-year period were reviewed. The causes of cancer of the male breast are no better understood, but major alterations in hormonal environment could be a significant factor. Some clinical characteristics correspond well with the results of other series. The median age at presentation was 61.7 years. The most frequent initial symptom was a painless mass, and the incidences of nipple discharge, central tumor location, and axillary node involvement were high. Males also had a higher incidence of local advancement which was associated with a longer delay in seeking treatment and small breast tissue. The pathologic type was infiltrating ductal type in all cases except one, and all cases showed favorable nuclear grade. Estrogen receptor analysis was performed from the tumor of 2 patients. Both of them showed a high receptor level. There was no locoregional relapse in 5 patients who received adjuvant radiotherapy in contrast to the 2 relapses in 3 patients who underwent surgery alone. And three of the five patients who received radiotherapy suffered from systemic metastasis which suggested the important role of adjuvant chemotherapy as well as radiotherapy. In light of the encouraging results about adjuvant chemotherapy in the treatment for female breast cancer with axillary lymph node involvement, it would be desirable to extend this policy to male breast cancer.

Adenocarcinoma↗
PubMed1988

Nucleotide sequence of the bovine gene for follicle-stimulating hormone beta-subunit.

The gene for the beta-subunit of follicle-stimulating hormone (FSH-beta) was isolated from a library of bovine DNA fragments cloned in bacteriophage gamma and the complete nucleotide sequence of the gene was determined. The bovine FSH-beta gene contains approximately 4000 nucleotides and consists of three exons separated by two intervening sequences. The transcription initiation site of the gene was mapped by nuclease protection experiments. Analysis of RNA species present in pituitary mRNA demonstrated the presence of a 4.0-kb RNA containing FSH-beta sequences, which is the appropriate size for the primary transcript of the gene. Comparison of nucleotide sequence of the 5'-flanking sequence of the FSH-beta gene to the 5'-flanking regions of other pituitary glycoprotein hormone genes reveals little sequence similarity.

Amino Acid Sequence↗