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Biomedical subjects

S Y Kim

Publications and source records attributed to S Y Kim.

At least 19 recordsLinked to original sources
PubMed1995

Highly active soluble processed forms of the transglutaminase 1 enzyme in epidermal keratinocytes.

The transglutaminase 1 (TGase 1) enzyme is required for the formation of a cornified cell envelope in epidermal keratinocytes. We show here that in addition to its membrane-anchored form, soluble forms of it are also important in keratinocytes. Proliferating cells contain soluble full-length enzyme of 106 kDa, but terminally differentiating cells contain a soluble 67-kDa form often complexed with a 33-kDa protein as well. The amino terminus of the 67 kDa form is residue 93 of the TGase 1 protein, corresponding to the site of proteolytic activation of the factor XIIIa TGase. The amino terminus of the 33-kDa protein is residue 573, corresponding to the site of a second proteolytic cleavage site of factor XIIIa, and of the site for proteolytic activation of the TGase 3 enzyme. The specific activity of the 67/33-kDa soluble complex is twice that of the soluble 67-kDa form and 10 times that of full-length TGase 1. The half-lives of the 67/33- and 106-kDa forms are about 7 or 20 h, respectively. Thus the TGase 1 enzyme is complex, since it exists in keratinocytes as multiple soluble forms, either intact or proteolytically processed at conserved sites, and which have varying specific activities and likely functions.

Amino Acid Sequence↗
PubMed1995

Structure and function of the HOX A1 human homeobox gene cDNA.

Homeobox genes code for transcription factors and are arranged in clusters, named A, B, C and D, found on four separate chromosomes in vertebrates. They contain a homeobox DNA sequence which codes for the homeodomain, a region of amino acids responsible for the DNA binding exhibited by these proteins. During embryonic development, the homeobox genes are both spatially and temporally regulated. In teratocarcinoma cell cultures, homeobox genes are regulated by retinoic acid (RA). The cDNAs from the first gene in the human HOX A cluster, HOX A1 (1.6), were cloned and the nucleotide sequence of a full-length cDNA was determined. It is highly homologous to its murine counterpart. Another HOX A1 cDNA was cloned, corresponding to an alternatively spliced form. In vitro translation of the full-length cDNA clone gave rise to a protein of 36 kDa. In PA-1 human teratocarcinoma cells HOX A1 is the earliest HOX A gene to be expressed after treatment with RA. To test whether HOX A1 could function as a early regulator of other HOX A cluster genes, we cotransfected into PA-1 human teratocarcinoma cells sense and antisense HOX A1 cDNAs expressed from an SV40 promoter with a 5.4-kb RA-sensitive HOX A4 (1.4) promoter-cat reporter. We found no effect of HOX A1 on the HOX A4 promoter. However, cotransfection of HOX A5 (1.3) was able to inhibit the HOX A4 promoter activity.

Alternative Splicing↗
PubMed1995

Involvement of the Na,K-ATPase in the induction of ion channels by palytoxin.

The effects of ouabain, ATP, and vanadate on palytoxin induction of ion channels were examined with the aim of elucidating the role of Na,K-ATPase in palytoxin action. Palytoxin-induced membrane depolarization of crayfish giant axons and single channel currents of frog erythrocytes and mouse neuroblastoma N1E-115 cells were examined using the intracellular microelectrode and patch-clamp techniques. External application of palytoxin in nanomolar concentrations induced depolarization in the crayfish giant axons, and the depolarization was inhibited by pretreatment of the axon with ouabain (10 microM). Internally perfused axons were less sensitive to palytoxin unless ATP (6 mM) was added internally. In patch-clamp experiments, picomolar palytoxin in the patch electrode induced single channels in both cell-attached and inside-out patches of erythrocytes and neuroblastoma cells. The induced channels had a conductance of about 10 pS, reversed near 0 mV in physiological saline solution, and was permeable to Na+, K+, Cs+, and NH4+, but not to choline. Single channel activities induced by palytoxin were inhibited by ouabain (10 microM) and vanadate (1 mM), but promoted by ATP (1 mM). The modulating effects of ouabain, vanadate, and ATP on palytoxin action suggest that the Na,K-ATPase is involved in the induction of single channels by palytoxin. Palytoxin-induced and ouabain-inhibitable single channels were observed in planar lipid bilayer incorporated with purified Na,K-ATPase. The results indicate that an interaction between palytoxin and Na,K-ATPase leads to opening of a 10-pS ion channel. They further raise the possibility that a channel structure may exist in the sodium pump which is uncovered by the action of palytoxin.

Acrylamides↗
PubMed1995

Effect of an inelastic aortic synthetic vascular graft on exercise hemodynamics.

This study compared aortic input impedance characteristics between patients with aortic interposition Dacron grafts placed for traumatic aortic injury and normal age-matched control subjects. All subjects were examined at rest and after treadmill exercise. Magnetic resonance imaging was conducted to rule out anatomic (stenosis) effects. Exercise increased characteristic impedance (ie, reduced aortic distensibility) by 29% and decreased total systemic arterial compliance by 21% in the patient group, whereas the normal control group showed insignificant change in these variables after exercise. Peripheral pressure wave reflection was reduced substantially with exercise (27%) in the control group, with much less reduction observed in the patient group. These abnormal vascular hemodynamics were associated with significantly high cardiac energetic costs in the patient group. A plausible explanation for the observed differences lies in the exaggerated vascular impedance mismatch between compliant aorta and inelastic graft, when cardiac output increases dramatically.

Adult↗
PubMed1995

How important is the role of the internal anal sphincter in fecal continence? An experimental study in dogs.

It is a generalized concept that the internal anal sphincter (IAS) plays a significant role in fecal continence by generating high pressure in the anal canal at rest and relaxation during rectal distention. Agreement also exists on the importance of internal sphincter-saving anoplasty on anorectal malformations in establishing anal continence. Twelve dogs were divided into four groups. Group 1, a control group, was subjected to a perirectal dissection only. Group 2 underwent the same perirectal dissection plus a 2-cm resection of the anal canal. Group 3 underwent the perirectal dissection plus a 4-cm resection of the anal canal, and group 4 underwent perirectal dissection and transposition of the anus to the posterolateral portion of the voluntary muscle mass. Clinical continence was evaluated, and manometric results were compared with preoperative measurements. All dogs in groups 1, 2, and 3 were clinically continent without soiling except one in group 3, and also manometric results showed minimal change between preoperative and postoperative anal pressure profiles. The transposed anus of group 4 showed continuous fecal soiling. The anal resting pressure (ARP) was also decreased but still existed in this group. This experimental study showed that the IAS contributes to the anal resting tone. However, resection of the IAS did not completely interfere with fecal continence. The smooth muscle of pulled-through rectum seemed to partly take over the function of the IAS.

Anal Canal↗
PubMed1995

Sestamibi parathyroid imaging.

Since the introduction of technetium-99m (99mTc) sestamibi (hexakis-2-methoxyisobutyl isonitrile) as a parathyroid imaging agent in 1989, many investigators using several different imaging protocols have reported uniformly excellent results for localization of parathyroid adenomas. Exact localization of hyperplastic parathyroid glands has not met with as much success. However, the results of multiple comparative studies suggest that the diagnostic utility of sestamibi protocols equals or exceeds other noninvasive, nonscintigraphic imaging strategies, including high-resolution ultrasound, computed tomography, and magnetic resonance imaging. Two different, but not necessarily mutually exclusive imaging strategies have been used: subtraction imaging using iodine-123 (123I) or 99mTc sodium pertechnetate as the thyroid agent, and sestamibi dual-phase imaging, which takes advantage of differential washout of sestamibi from thyroid and parathyroid tissue. Sestamibi subtraction imaging has been shown to have greater sensitivity for abnormal parathyroid glands compared with thallium-201 subtraction imaging using pooled data, 87% versus 71%, respectively. Dual-phase sestamibi imaging protocols are much more variable in their conduct and have a much greater variability in sensitivity, 43% to 91%, but with a pooled sensitivity of 73%. Data suggest that dual phase techniques are at least as sensitive, and in optimized protocols, superior to, thallium-201 subtraction techniques. This superiority is attributed to the favorable washout kinetics of sestamibi and the superior imaging characteristics of the 99mTc label. Specificity and positive predictive value for both sestamibi techniques are very high, typically greater than 90% and at least equal to thallium-subtraction protocols, although specificity may be slightly lower for sestamibi subtraction techniques. Therefore, sestamibi protocols are the scintigraphic procedure of choice for parathyroid imaging. Dual-phase sestamibi protocols are more robust and lend themselves to single photon emission computer tomography (SPECT) imaging, and may be followed sequentially by subtraction techniques if results are inconclusive. Despite the excellent results of sestamibi parathyroid imaging, it is unclear whether this accuracy can compete with the even better success of an experienced surgeon in initial surgeries for hyperparathyroidism, and routine preoperative imaging before initial surgery is still controversial. However, sestamibi parathyroid imaging is an excellent addition to a correlative imaging approach in reoperations for persistent and recurrent hyperparathyroidism.

Adenoma↗
PubMed1995

Human mesangial cell production of monocyte chemoattractant protein-1: modulation by lovastatin.

Macrophages play a critical role in the progression of clinical and experimental glomerular injury. Serum-stimulated human fetal mesangial cells in culture produce a chemotactic factor that is monocyte-selective. This chemotactic factor is most likely monocyte chemoattractant protein-1 (MCP-1) as a monoclonal antibody directed against MCP-1, but not an irrelevant antibody, suppressed the mesangial cell-derived chemotactic activity. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase by lovastatin resulted in a reduction of the mesangial cell-derived chemotactic activity as well as MCP-1 mRNA expression. The inhibitory effects of lovastatin in the presence of exogenous cholesterol were reversed by mevalonate, suggesting a role for isoprenoid intermediates of the mevalonate pathway and/or isoprenylated proteins in mesangial cell MCP-1 regulation. These findings suggest an additional mechanism by which HMG-CoA reductase inhibition in vivo may reduce glomerular injury.

Cells, Cultured↗
PubMed1995

Expression of transglutaminase 1 in human epidermis.

To explore the expression and function of the membrane-associated or type I transglutaminase (TGase1) in human epidermis, we have made a new antihuman TGase1 antibody in goats elicited against a purified active recombinant protein expressed in bacteria. By use of Western blotting and immunoprecipitation methods, the antibody reacted with high specificity with only the TGase1 activity of the epidermis and in cultured keratinocytes. By indirect immunofluorescence, the antibody decorated the entire epidermis, including the basal layer, with some potentiation of the granular layer. However, these staining properties are quite different from those of a widely used, commercially available TGase1 monoclonal antibody (termed B.C1), which decorates the granular layers of the epidermis. By Western blotting, it identifies the TGase1 protein band only weakly, but recognizes strongly a group of bands of 15-20 kDa, two of which by amino acid analysis and amino acid sequencing are the small proline-rich (SPR) 1 and SPR2 proteins, also expressed in epidermal and epithelial tissues. Together with a series of blocking experiments with TGase1 proteins and synthetic peptides, these data reveal that the major epitope of the B.C1 antibody most likely resides on the amino-terminus of these two SPR proteins rather than on TGase1. Further studies will now be necessary to determine the role(s) of TGase1 during the different stages of development and differentiation in the epidermis.

Adult↗
PubMed1995

Discrepancy of recovery times related to potency between atracurium and mivacurium simultaneously administered in isolated forearms.

Recovery from potent non-depolarising muscle relaxants is slower than from the less potent agents. However, recovery from mivacurium, which is more potent than atracurium, is faster than from atracurium following systemic administration. In an attempt to confirm this discrepancy we compared recovery times following simultaneous administration of equipotent doses of atracurium and mivacurium into the isolated forearms of human volunteers (n = 10). This method enabled us to study the interaction of muscle relaxants with receptors at the neuromuscular junction separated from the effects of plasma drug concentration. In these experiments, the recovery times from maximum block to 50% recovery of control twitch height were significantly longer with mivacurium than with atracurium (mean 25.2(SD 4.7) versus 22.6(3.1) min, p < 0.01). We found that the evidence that mivacurium has a slower recovery than the less potent atracurium may be true using the bilateral, isolated forearm technique and that the discrepancy might be due to a difference in the pharmacokinetic variables of the two drugs.

Adult↗
PubMed1995

Stress increases brain-derived neurotropic factor messenger ribonucleic acid in the hypothalamus and pituitary.

Brain-derived neurotropic factor (BDNF) is a member of the nerve growth factor family that is important for neuronal survival and plasticity. We recently demonstrated that stress decreases BDNF messenger RNA (mRNA) levels in the hippocampus, which raises the possibility that BDNF may play a role in regulation of the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine whether BDNF expression is present and influenced by stress in other brain areas relevant to control of the hypothalamic-pituitary-adrenal axis. Using in situ hybridization, we found that BDNF mRNA is present in the parvocellular portion of the hypothalamic paraventricular nucleus (PVN), the lateral hypothalamus, and the anterior and neurointermediate lobes of the pituitary in rats. Acute (2-h) or repeated immobilization stress increased BDNF mRNA in all of these areas. This was in distinct contrast to stress-induced decreases in extrahypothalamic areas, including the basolateral amygdala, claustrum, and cingulate cortex as well as the hippocampus. BDNF was expressed in both CRF and TRH neurons in the PVN. Reducing glucocorticoid or thyroid negative feedback increased BDNF mRNA in the PVN and anterior pituitary, but not in the neurointermediate lobe. These results suggest that BDNF is a stress-responsive intercellular messenger that may be an important component of the stress response.

Adrenal Glands↗
PubMed1995

Profound hypotension immediately following insertion of methyl methacrylate during bipolar endoprosthesis in a patient with long-term levodopa-treated paralysis agitans.

Insertion of methyl methacrylate polymer into newly reamed bony cavities has sometimes resulted in profound hypotension, cardiac arrest, or sudden death which are more common in patients with hemodynamic instability or hypovolemia. In paralysis agitans(Parkinson's disease), dramatic worsening of the disease often occurs when another illness or trauma accompanies it. And it is possible that chronic medication with levodopa can cause the loss of ability to support blood pressure. So, it involves some risk to use methyl methacrylate in chronic levodopa-treated paralysis agitans. We present a case of paralysis agitans who demonstrated profound hypotension immediately following insertion of methyl methacrylate polymer in spite of normovolemia and proper anesthetic management.

Aged↗
PubMed1995

Changes in adhesive force between the retina and the retinal pigment epithelium by laser photocoagulation in rabbits.

A closed eyeball model was designed to estimate the chorioretinal adhesion of the laser-photocoagulated region. We used it to measure the duration of development of retinal detachment during vitrectomy before and after killing the test rabbits. During testing, negative pressure was applied into the vitreous cavity of the pigmented rabbits. Laser burns were produced in the posterior retina by exposure to an argon blue-green laser beam with a focus diameter of 200 microns of 0.1 to 0.2 second duration and 150 to 250 mW intensity. One hour and one, two, five, seven and fourteen days following laser photocoagulation, vitrectomy was done with a cutting rate of 500 per minute, aspiration pressure of 50 mmHg and infusion pressure of 55.2 mmHg. After core vitrectomy, the rabbit was killed with an intravenous bolus of 100 mg sodium pentobarbital solution. After killing the rabbit, the vitreous cavity was continuously aspirated under the pressure of 25 mmHg while the infusion was stopped. The changes of the fundus, especially development of retinal detachment, were observed in the laser-treated and untreated regions before and after killing the rabbit. When retinal detachment was noted anywhere before killing the rabbit, this postmortem change was not observed. One hour following laser photocoagulation, the laser-treated retina was detached during core vitrectomy before killing the rabbit, and the untreated area was not detached. One day following photocoagulation, the retina was intact before killing the rabbit. After killing the rabbit, the laser-treated retina was detached in four minutes and the untreated retina in 18 minutes postmortem.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesiveness↗
PubMed1995

Cytotoxic potential of monoalkylation products between mitomycins and DNA: studies of decarbamoyl mitomycin C in wild-type and repair-deficient cell lines.

Hypoxic regions in solid neoplasms have been associated with tumor recurrence and resistance to several cancer treatment modalities including radiation therapy. Various strategies have been designed to target these resistant cells, including the use of the bioreductive alkylating agent mitomycin C (MC), which exerts preferential cytotoxicity under hypoxic conditions in most cell lines. Analyses of the mechanism of action of MC indicate that this drug can form cross-links with DNA; it is currently thought that this bisadduct is the critical lesion responsible for inhibiting DNA synthesis. Computer-generated models suggest that the MC adduct fits snugly into the minor groove of B-DNA without imposing major distortion on the structure of the DNA molecule. To gain additional insight into the role of cross-linkage in the cytotoxicity of MC, we studied the analogue, decarbomoyl mitomycin C (DMC). The structure of DMC is identical to that of MC with the exception of the substitution of the carbamoyl group at the C-10 position by a nonalkylating hydroxyl group (-OH); this alteration would be expected to prevent DMC from forming bisadducts with DNA. In chemical systems, DMC produces only DNA monoadducts. If indeed it is the MC-DNA cross-links which are responsible for cell kill, one would predict DMC to be less cytotoxic than MC. However, tissue culture studies using DMC revealed that DMC is at least as toxic as MC to EMT6 mouse mammary tumor cells and to wild-type AA8 Chinese hamster ovary (CHO) cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Interphase cytogenetics in paraffin sections of lung tumors by non-isotopic in situ hybridization. Mapping genotype/phenotype heterogeneity.

To better understand the relationship between specific chromosome changes found in human lung tumors and their phenotypic consequences at the tissue level, an in situ hybridization procedure was optimized for use on formalin-fixed paraffin-embedded tissue sections of human lung tumors. Pretreatment heating of sections, pepsin concentration, duration of pepsin treatment, hybridization conditions, and posthybridization washing conditions were varied to determine optimum conditions. The deparaffinized sections were stained with centromeric probes for chromosomes 7 and 17, and a chromosome index for each tumor was derived by dividing the mean number of chromosome signals found on the tumor cells by the mean number of chromosome signals on normal cells (lymphocytes and fibroblasts) in the same section. This chromosome index was then compared with the DNA index determined in an adjacent section by Feulgen staining followed by image analysis quantitation. The chromosome index correlated well with the DNA index, but in some cases, chromosome 7, or 17 in other cases, was either over- or under-represented compared with the corresponding DNA index. In addition, chromosome and DNA alterations were shown to be differentially expressed within the same tissue section, correlating with a change in tumor differentiation status. These results suggest that in situ hybridization will prove to be an important tool for determining the underlying genetic basis for tissue phenotype heterogeneity by allowing genetic determinations to be made on paraffin-embedded tissue sections where tumor histological architecture is preserved.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Determination of biomarkers for intermediate end points in chemoprevention trials.

Renewed interest is being directed toward chemoprevention as a means of reducing cancer mortality. To overcome the inherent problems associated with using cancer development as a study end point, there has recently been a great surge of interest in defining the biomarkers associated with specific stages of the carcinogenic process as intermediate end points. We have detailed the evidence supporting the concept of field cancerization, a concept of general importance that is probably applicable to carcinogenesis and chemoprevention at many organ sites in humans, and presented results of tests of the potentially useful biomarkers proliferating cell nuclear antigen and blood group antigen. Because microassay techniques are more readily applicable to small biopsy samples, further expansion of these studies and exploration of panels of additional biomarkers are expected to generate exciting results in the field of chemoprevention.

ABO Blood-Group System↗
PubMed1992

Structure and organization of the human transglutaminase 1 gene.

Membrane-associated transglutaminases (TGase1) have recently been found to be common in mammalian cells, but it is not clear whether these derive from the same or different genes. In order to determine the complexity of this system, we have isolated and characterized the human gene (TGM1). The gene of 14,133 base pairs was found to contain 15 exons spliced by 14 introns. Interestingly, the positions of these introns have been conserved in comparison with the genes of two other transglutaminase-like activities described in the literature, but the TGM1 gene is by far the smallest characterized to date because its introns are relatively smaller. On the other hand, the TGase1 enzyme is the largest known transglutaminase (about 90 kDa), apparently because its gene acquired tracts that encode additional sequences on its amino and carboxyl termini that confer its unique properties. Southern blot analyses of total human genomic DNA cut with several restriction enzymes reveal only one band. Use of human-rodent cell hybrid panels and chromosomal in situ hybridization with biotin-labeled probes revealed that the human TGM1 gene maps to chromosome position 14q11.2-13. Such data suggest there is a single gene copy per haploid human genome. Comparisons of sequence identities and homologies indicate that the transglutaminase family of genes arose by duplications and subsequent divergent evolution from a common ancestor but later became scattered in the human genome. Although our present Southern blot and chromosomal localization studies revealed no restriction fragment length polymorphisms, comparisons of published sequences and our genomic clone indicate there are two sequence variants for TGase1 within the human population. The rare smaller variant contains a two-nucleotide deletion near the 5'-end, uses an alternate initiation codon, and differs from the common larger variant only in the first 15 amino acids. Furthermore, the DNA sequences of intron 14 possess several tracts of dinucleotide repeats that by polymerase chain reaction analysis show wide size polymorphism within the human population. Accordingly, this gene system constitutes a useful polymorphic marker for genetic linkage analyses.

Amino Acid Sequence↗