Biomedical subjects

T W Kim

Publications and source records attributed to T W Kim.

At least 73 records · Page 4Linked to original sources

PubMed1996

[The replacement processes of growth plate cartilage to bone in endochondral ossification of mandibular condyle].

Using 3-week-old male beagle dogs, we examined the cartilage-bone replacement processes in the mandibular condyle by means of light and electron microscopy. Calcification of the cartilage matrix occurred in the central area of the longitudinal septa, but not in the transverse septa. Perivascular mononuclear cells absorbed the transverse septa which initiated the opening of the chondrocytic lacunae. These cells phagocytosed septal cartilage fragments. Shortly thereafter, a thin bone layer was deposited on the remaining longitudinal septa by invading osteoblasts. Osteoclasts in lacunae developed neither ruffled borders nor clear zones in the cartilage matrix, but once the bone layer has been deposited in the remaining cartilage, these structures formed. Our results suggest that the cartilage-bone replacement in mandibular condyle involves three sequential processes: 1) degradation and phagocytosis of cartilage fragments in the transverse septa by mononuclear cells, 2) bone deposition over the remaining longitudinal septa, and 3) degradation of both calcified cartilage and bone by osteoclasts.

Animals↗

PubMed1995

Deficiency of brain synaptic dystrophin in human Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is characterized by a defect in dystrophin, a high molecular weight protein that is located predominantly in muscle, but which has been detected in brain. Brain dystrophin has been localized to the synapse, in the postsynaptic density (PSD), and is absent in the mdx mouse, an animal model of human DMD. To define the potential pathogenic role of dystrophin deficiency in cognitive impairment, we examined the protein in human DMD brain. The 427-kd dystrophin was absent in the PSD from DMD brain, but was normally expressed in the brain from an age-matched control subject. Our findings indicate that dystrophin is deficient in human DMD cortical synapses and provide a potential pathogenic mechanism for cognitive impairment.

Brain Chemistry↗

PubMed1995

Selective localization of amyloid precursor-like protein 1 in the cerebral cortex postsynaptic density.

Senile plaques, a hallmark of Alzheimer's disease (AD), contain amyloid beta-peptide (A beta), which is generated from the larger amyloid beta protein precursor (APP). In addition to APP, several APP-related proteins have been recently identified in different organisms, including Drosophila amyloid precursor protein-like protein (APPL). Deficiency of APPL causes behavioral deficits in Drosophila, implicating a role in brain function. Moreover, mouse and human cDNA clones encoding amyloid precursor-like proteins (APLP1 and APLP2) have been identified and exhibit extensive sequence similarity to the APPL and APP genes. To define the potential role of APLP in the mammalian brain, we sought to directly localize APLP1 within the complex cortical synaptic structure. We focused on the postsynaptic density (PSD), which appears to be central to synaptic function. We now report that the 90 kDa APLP1, the first known APLP, is localized to the PSD from rat and human cerebral cortex. APLP1 increased during cortical synaptic development, suggesting a role in synaptogenesis or synaptic maturation. In contrast, APP was predominantly expressed in the synaptic membrane fraction, but was barely detectable in the PSD, including different subcellular distributions of APP and APLP1. Our observations raise the possibility that APLP1, a homologue of APPL, which appears to be necessary for normal behavior in Drosophila, participates in brain synaptic function in mammals.

Amyloid beta-Protein Precursor↗

PubMed1995

Lack of effect of retinoic acid and fluocinolone acetonide on mirex tumor promotion indicates a novel mirex mechanism.

Mirex, a halogenated hydrocarbon, is a potent skin tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. In the present study retinoic acid (RA) and fluocinolone acetonide (FA), classical inhibitors of phorbol ester- and non-phorbol ester-type skin tumor promoters, were examined for their ability to inhibit mirex tumor promotion. Female CD-1 mice were initiated with 200 nmol DMBA and promoted with equipotent promoting doses of either 5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) or 200 nmol mirex twice weekly for 25 weeks and RA (2(1 or 5 nmol), FA (0.5 or 2 nmol) or acetone were applied 30 min prior to each TPA or mirex dose. TPA-promoted papilloma formation was strongly inhibited by > 70% with both doses of RA and by > 90% with both doses of FA. In contrast, mirex-promoted papilloma formation was not inhibited by either dose of RA or 0.5 nmol FA and 2 nmol FA weakly inhibited mirex-promoted papillomas by only 32%. TPA- and mirex-promoted papillomas that were refractory to RA and FA demonstrated the same incidence of Ha-ras mutation as TPA- or mirex-promoted papillomas without RA and FA treatment, further indicating that the inhibitory activity of RA and FA is promoter-dependent and not solely dependent on mutant Ha-ras. FA (2 nmol) treatment completely abolished TPA-induced epidermal hyperplasia and proliferating cell nuclear antigen (PCNA) S phase-positive cells, however, FA had no inhibitory effect on the weak proliferative response induced by mirex. Collectively, these results indicate that the promotional activity of mirex, as well as its weak proliferative response, result from a distinct promoter mechanism and/or that mirex promotes a unique population of epidermal cells that are insensitive to FA and RA and cannot be distinguished by their mutant Ha-ras genotype.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1994

Synergistic interaction between the non-phorbol ester-type promoter mirex and 12-O-tetradecanoylphorbol-13-acetate in mouse skin tumor promotion.

Mirex, an organochlorine pesticide and non-genotoxic rodent hepatocarcinogen, is also a potent non-phorbol ester-type promoter of mouse skin tumors. Mirex, unlike most other skin tumor promoters, is not a significant epidermal hyperplasiogen even at a maximally promoting dose (200 nmol). Experiments described here examined whether tumor promotion by mirex and 12-O-tetradecanoylphorbol-13-acetate (TPA) are mediated through different mechanisms as indicated by their additivity when co-applied to 7,12-dimethyl-benz[a]anthracene (DMBA, 200 nmol)-initiated female CD-1 mouse skin. Instead of the additive response of 14 plus 5 tumors/mouse predicted from mice promoted for 20 weeks (2x/week) with either mirex (200 nmol) or TPA (2 nmol) respectively, their co-application yielded 35 tumors/mouse. This synergy with TPA was specific to mirex since a structurally related compound, chlordecone (Kepone) was inactive. Mirex plus TPA-promoted papillomas contained a c-Ha-ras A182-->T mutation as frequently (13/14) as those promoted by mirex or TPA alone, suggesting that these DMBA-initiated/co-promoted papillomas were not atypical in this genotypic marker. Promotional synergy with mirex was only observed with a submaximal promoting dose of 2 nmol TPA; 5 or 8 nmol TPA plus mirex gave additive or less tumor multiplicities. This synergistic multiplicity with mirex plus 2 nmol TPA (35 tumors/mouse) approximated the sum of individual responses to 200 nmol mirex (14 tumors/mouse) and the maximally promoting dose of TPA (12 nmol), 24 tumors/mouse, suggesting that mirex potentiated the promotional activity of TPA, as well as promoted through a mirex-specific mechanism. Epidermal DNA synthesis induced by 2 nmol TPA was potentiated by mirex, further supporting a role for mirex in potentiation of epidermal TPA activity. Collectively, these studies suggest that mirex affects two possibly related responses: (i) promotion through a distinct mirex-specific mechanism, and (ii) potentiation of a mechanism mediating the promotional activity of TPA.

Adenine↗

PubMed1992

Detection of dystrophin in the postsynaptic density of rat brain and deficiency in a mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a common, lethal, chromosome X-linked inherited disease. Moderate cognitive impairment is a feature of DMD, but the underlying mechanisms are unknown. DMD is characterized by a defect in a protein, dystrophin, that is located predominantly in muscle but has been detected in brain. We sought to directly localize dystrophin within the complex synaptic structure of the cerebral cortex by focusing on the postsynaptic density (PSD), which appears to be central to synaptic function. We report that a specific anti-dystrophin antibody (anti 6-10) recognizes three distinct proteins in the purified PSD: the 400-kDa dystrophin and two previously unidentified dystrophin-related proteins of 120 and 110 kDa. These proteins exhibited differential regional expression in PSDs from cerebral cortex, cerebellum, and olfactory bulb. In the cortical PSD, the 400-kDa dystrophin was predominant, whereas the 120-kDa protein was the major species in cerebellum and olfactory bulb PSDs. The three proteins were differentially expressed in the PSD during cortical development: the 400-kDa protein exhibited a selective 9-fold increase during postnatal days 7 to 10, suggesting a normal physiological role in synaptic maturation. The PSD from the mdx mouse, a model of human DMD, contained no detectable 400-kDa dystrophin but expressed the two dystrophin-related proteins. Our results indicate that brain dystrophins are localized to the PSD, potentially as three isoforms, and raise the possibility that cognitive abnormalities in DMD are attributable to synaptic dysfunction associated with deficits in brain dystrophin molecules.

Animals↗

PubMed1992

Synergistic effect between tannic acid and X-rays detected by the Tradescantia-micronucleus assay.

Tannic acid (TA), a complex mixture of polyphenolics, exhibited synergism with 4-nitroquinoline 1-oxide (4-NQO), methyl methanesulfonate (MMS) and cis-platinum (cis-DDP) in a recent study on w/w+ somatic mutation in the eye pigment of Drosophila, although several studies indicated that tannic acid is an antimutagen in cultured mammalian cells. The goal of this study was to determine the genotoxicity of tannic acid alone and its possible synergistic effect with X-rays using the Tradescantia-micronucleus (Trad-MCN) bioassay. Plant cuttings were irradiated with 35 R of X-rays (80 kV, 5 mA) and followed by a series of increasing dosages (0.1, 0.5, 0.75, 1.0, 1.25, 1.50 mM) of TA treatment (24 h) and in some cases TA treatment was followed by X-irradiation. Inflorescences were fixed after a 24-h recovery period and slides were prepared for scoring MCN frequencies. Four series of experiments were conducted and the results of Trad-MCN tests on X-rays alone yielded an average of 47.5 MCN/100 tetrads (SE = 6.08), and 1.0 mM TA alone yielded an average of 8.95 MCN/100 tetrads (SE = 0.1), while the combined treatments (35 R X-rays plus 1.0 mM TA) yielded an average of 126.95 MCM/100 tetrads (SE = 13.69). The MCN frequency of the negative control was around 4.6 MCN/100 tetrads (SE = 0.75). This kind of synergism was exhibited through all the increasing dosages around 1.0 mM or higher. The synergistic effect of these two agents remained at the same level when TA was followed by X-irradiation. When a 12-h repairing period was allowed after X-irradiation in the combined treatment, the MCN frequency was similar to that of the X-ray treatment alone. The synergistic effect in the cases where the TA exposure was given immediately after X-irradiation could be attributed to the inhibitory action of TA on the DNA repair process.

Hydrolyzable Tannins↗

PubMed1992

Synergistic and antagonistic effects on genotoxicity of chemicals commonly found in hazardous waste sites.

Synergistic and antagonistic effects on genotoxicity of mixtures of four chemicals; i.e., lead tetraacetate (LTA), arsenic trioxide (ATO), dieldrin (DED), and tetrachloroethylene (TCE), were evaluated by the Tradescantia-micronucleus (Trad-MCN) assay. The chemicals were mixed in ratios of 1:1, 1:2 and 2:1 for mixtures of two chemicals and 1:1:1 each for three chemicals. The concentration of stock solution of these chemicals was around the minimum effective dose (MED) or below the MED for these chemicals as reported by Sandhu et al. (1989). Treatments were applied to plant cuttings by hydroponic uptake of the mixed solutions through the stems of the plant for 30 h followed by fixation of the flower buds in aceto-alcohol (1:3 ratio) without a recovery period. Microslides were prepared for scoring MCN frequencies. Results of two series of repeated experiments indicated that all mixtures of LTA/ATO exhibited antagonistic effects. On the other hand, all mixtures of TCE and DED exhibited synergistic effect. These data indicate that for evaluating biological hazards at chemical waste sites, it is prudent to evaluate the genotoxicity of complex chemical mixtures as these exist in nature because the biological effects based on evaluating individual chemicals may not be true predictors of the interactive effects of the pollutants.

Arsenic↗

PubMed1990

Determination of cysteine on low-density lipoproteins using the fluorescent probe, 5-iodoacetamidofluoresceine.

Using the fluorescent sulfhydryl probe, 5-iodoacetamidofluoresceine, to label the free sulfhydryl of low-density lipoprotein, the positions of two cysteine residues in apolipoprotein B were located. The tryptic peptides containing the fluorescent probe were isolated by high-performance liquid chromatography systems and sequenced by automatic techniques. The free cysteine residues of apolipoprotein B-100 on low-density lipoprotein are located at positions 3734 and 4190, either or both of which can potentially form a disulfide linkage with apolipoprotein(a) in lipoprotein(a).

Amino Acid Sequence↗

PubMed1990

Isolation and characterization of sulfhydryl and disulfide peptides of human apolipoprotein B-100.

Twenty-three of the 25 cysteine residues in apolipoprotein B-100 have been isolated directly from tryptic or peptic peptide mixtures. Sixteen cysteine residues exist in disulfide forms: Cys-1-Cys-3, Cys-2-Cys-4, Cys-5-Cys-6, Cys-7-Cys-8, Cys-9-Cys-10, Cys-11-Cys-12, Cys-13-Cys-14, and Cys-20-Cys-21. All of these except Cys-20-Cys-21 are recently discovered disulfide linkages. In addition to Cys-22 and Cys-24, which have been described as sulfhydryls on low density lipoprotein, Cys-15 to Cys-18 and Cys-23 are in the reduced form. Cys-19 and Cys-25 are not yet confirmed. Our results revealed that all identified disulfide linkages are located in the trypsin-releasable regions and that all except Cys-1-Cys-3 and Cys-2-Cys-4 are linked to the neighboring cysteine. We propose a linear model of apolipoprotein B-100 in low density lipoprotein that wraps around the low density lipoprotein molecule.

Amino Acid Sequence↗

PubMed1989

Structure and conformational analysis of lipid-associating peptides of apolipoprotein B-100 produced by trypsinolysis.

Apolipoprotein B-100 (apo B-100) contains putative lipid-associating regions that are, in part, responsible for its overall structure in human plasma low-density lipoproteins. Some of these regions have been identified by reassembly of the total tryptic peptides of apo B-100 with bovine brain sphingomyelin, 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) and dimyristoylphosphatidylcholine (DPMC). Although more than 500 tryptic peptides are predicted from the known number of arginines and lysines in apo B-100, significant amounts of only 13 peptides spontaneously associate with all three phospholipids. These peptides share some structural characteristics, as predicted by several algorithms, that distinguish them from the water-soluble apolipoproteins. Most apolipoproteins associate with lipids via amphipathic helices and are highly helical in native and reassembled lipoproteins. Analysis of all apo B-100 lipophilic peptides by circular dichroism and by use of a predictive algorithm reveals no evidence of amphipathic helices. Although the predictive algorithm suggested that the lipophilic peptides of apo B-100 contain the sequence determinants for beta-sheet, no spectroscopic evidence for this structure was found. We conclude that the lipophilic regions of apo B-100 liberated by trypsinolysis are highly hydrophobic, although their secondary structures do not fit any simple model.

Amino Acid Sequence↗

PubMed1989

Resolution of secondary amyloidosis 14 years after adequate chemotherapy for skeletal tuberculosis.

Despite available chemotherapy, survival of patients with skeletal tuberculosis and secondary amyloidosis for more than five years is extremely unusual. We have described a patient with inadequately treated tuberculous osteomyelitis and later concomitant pulmonary tuberculosis and secondary amyloidosis. After a prolonged course of antituberculous chemotherapy, the patient was found to be cured of the tuberculosis and to have complete resolution of the amyloidosis 14 years after the diagnosis.

Aged↗

PubMed1989

Comprehensive employment preparation for adolescents with developmental disabilities: an empirical paradigm.

This paper presents a comprehensive employment preparation intervention for adolescents with developmental disabilities. Vocational preparation is viewed in terms of the development of job and related psychosocial skills. The Comprehensive Employment Preparation program is designed to help youth and young adults with developmental disabilities acquire the skills necessary to prepare them for effective functioning as self-sustaining, working members of society. Substantial research indicates that social, problem-solving and employment-seeking skills are significant factors in attaining and maintaining employment. At this time, relevant literature clearly reveals that progress is being made in assessing individual deficiencies and programs for development of improved social competency. Future policy and research issues are reviewed.

Adolescent↗

PubMed1987

The complete amino acid sequence of proapolipoprotein A-I of chicken high density lipoproteins.

The complete amino acid sequence of proapolipoprotein (proapo) A-I of chicken high density lipoproteins was determined by sequencing overlapping peptides produced by trypsin, S. aureus V8 protease, and cyanogen bromide cleavage. There are 240 amino acid residues in mature chicken apoA-I. By direct sequence analysis of a cyanogen bromide peptide, we also determined the sequence of a 6-amino-acid prosegment which is present at approx. 10% the molar amount of the mature peptide in chicken plasma. Sequence comparison among apoA-I from chicken, human, rabbit, dog and rat, and secondary structure analysis indicate that while the degree of sequence homology is only moderate (less than 50% between chicken and man), there is good conservation of apoA-I secondary structure, especially in the N-terminal two-thirds of the protein in these widely separated species.

Amino Acid Sequence↗

PubMed1986

The rib cage in normal and emphysematous subjects: a roentgenographic approach.

The configuration and motion of the bony rib cage were studied from lateral chest roentgenograms in 10 young normal subjects (YN), 12 elderly normal subjects, and 12 hyperinflated emphysematous patients [chronic obstructive pulmonary disease subjects (COPD), mean total lung capacity (TLC) 133% of predicted]. The acute angles formed by the fourth through seventh ribs with an axial reference plane were measured at residual volume, functional residual capacity, and TLC in both supine and standing positions and correlated with corresponding lung volumes. both rib angles (RA) and changes in RA with lung volume were greatest with the fourth rib and decreased progressively going down (caudad) the chest. At TLC the RA of upper ribs was significantly less in EN and significantly greater in COPD than in YN. RA's were greater supine than standing. When RA information was used together with autopsy data on the angles formed by intercostal muscles with adjacent ribs, intercostal muscle lengths in hyperinflation could be calculated. Computed intercostal muscle length data suggested that hyperinflation should not be associated with degrees of intercostal muscle shortening or overstretching, that would interfere seriously with tension generation.

Adult↗

PubMed1985

Myxoid liposarcoma mimicking fluid density.

A case of liposarcoma of the liver capsule initially presenting as massive pleural effusion and ascites is reported. The chest radiograph, computed tomographic scan, and sonogram are emphasized.

Aged↗

PubMed1985

Clinical trial of cefotaxime in patients with typhoid fever.

In 45 patients in whom typhoid fever was confirmed by culture of a blood sample, cefotaxime (1 gm BID) was administered intravenously for four days; if defervescence did not occur by day 5, the dosage was increased to 2 gm BID until defervescence, when it was reduced to 1 gm BID until discharge. On average, defervescence occurred on day 7 (range, day 3 to day 14), requiring a total dose of 31 gm (range, 12 to 60 gm) of cefotaxime. Relapse, occurring in three patients, was treated with co-trimoxazole. The duration of cefotaxime therapy was longer than therapy with chloramphenicol but without the risk of bone marrow depression.

Adolescent↗

PubMed1977

Sacral chordoma. A rare cause of chronic pelvic and low-back pain.

A case of sacral chordoma causing chronic, persistant low-back pain for 5 years is reported. This tumor was palpable on pelvic and rectal examination in the presacral area. Early excision is the treatment of choice for this slow growing tumor of primitive notochordal origin. Diagnosis is often late and incomplete surgical excision leads to local recurrence and eventual death. Knowledge of the existence of this rare condition, together with careful pelvic and rectal examination, are the importnat keys to diagnosis and possible curative treatment.

Adult↗