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Biomedical subjects

K M Kim

Publications and source records attributed to K M Kim.

At least 145 records · Page 8Linked to original sources
PubMed1996

Negative signaling in B cells by surface immunoglobulins.

Cross-linking of surface immunoglobulins generates negative signals that cause B-cell death unless appropriate rescue signals are provided. Surface IgM is the main transducer of the negative signaling, but surface IgD and IgG may also transduce negative signaling when cross-linked intensively. In the surface IgM+, IgD+ human malignant B lymphoma cell lines B104 and DND-39, cross-linking of surface IgM by anti-IgM antibodies induced cell death. Anti-IgM antibody-induced B104 cell death was inhibited by stimulation with alpha- and beta-interferons but not stimulation with anti-CD40 antibody or IL-4, whereas anti-IgM antibody-induced DND-39 cell death was inhibited by stimulation with anti-CD40 antibody but not stimulation with alpha- and beta-interferons. Anti-IgM antibody-stimulated B104 cells had morphologic features compatible with necrosis, whereas anti-IgM antibody-stimulated DND-39 cells showed morphologic features of apoptosis. CD11a/CD54-dependent cell adhesion induced by stimulation with anti-CD40 antibody was involved in anti-CD40 antibody-mediated inhibition of anti-IgM antibody-induced DND-39 cells. In normal human mature B cells, cross-linking of surface IgM induced different signaling consequences, including DNA synthesis or cell division (positive signaling) or cell cycle arrest or death (negative signaling). In this system, too, CD40-transduced signal inhibited anti-IgM antibody-induced negative signaling, and CD11a/CD54-dependent cell adhesion played a role in the rescue process. It is suggested that quantitatively different intensities of surface IgM cross-linking induce qualitatively different signaling consequences; relatively weak cross-linking may induce DNA synthesis; moderate cross-linking may induce DNA synthesis with cell cycle arrest at the G2/M interphase; and intense cross-linking may induce apoptotic cell death. The reasons for this difference are not yet known. Further elucidation of the molecular mechanisms responsible for surface IgM-mediated negative signaling and its rescue signaling may contribute toward development of therapy for allergic disorders by artificial modulation of specific immunoglobulin production.

Animals↗
PubMed1996

Chemotherapy versus transplants for acute myelogenous leukemia in second remission.

The best therapy for persons with acute myelogenous leukemia (AML) in 2nd remission is unknown. Bone marrow transplants from an HLA-identical sibling are reported to be better than chemotherapy but this is controversial. The objective of the study was to compare 3-year leukemia-free survival (LFS) in comparable subjects receiving chemotherapy or a transplant. 485 persons with AML in 2nd remission were studied. The chemotherapy cohort included 244 persons treated on trials of the British Medical Research Council, Eastern Cooperative Oncology Group and MD Anderson Hospital. The transplant cohort included 257 persons transplanted worldwide and reported to the international Bone Marrow Transplant Registry (16 were also chemotherapy subjects.) Subjects were selected for comparable age and year of treatment. Preliminary analyses identified two factors correlated with LFS: age < or = or > 30 years and 1st remission duration < or = or > 1 year; subsequent analyses were partitioned accordingly. Three-year probabilities of treatment-related mortality with chemotherapy and transplants were 7% (95% confidence interval, 3-15%) vs 56% (49-63%). Three-year leukemia relapse probabilities were 81% (74-86%) vs 41% (33-49%). Three-year probabilities of LFS were 17% (12-23%) vs 26 (20-32%). Cohort analysis showed significantly higher LFS with transplants vs chemotherapy in persons < or = 30 years and 1st remissions > 1 year (41% (29-53%) vs 17% (7-32%); P = 0.017) and those in > 30 years with 1st remissions < or = 1 year (18% (9-29%) vs 7% (2-16%); P = 0.046). Others had comparable LFS with both treatments. These data indicate better LFS with HLA-identical sibling transplants than chemotherapy in some persons with AML in 2nd remission.

Adolescent↗
PubMed1996

Determinants of weddellite formation: chondroitin sulfates and citrate determine weddellite formation in vitro.

In synthetic urine (SU), addition of oxalate tends to form monohydrates of calcium oxalate. However, addition of oxalate to natural urine preferably forms calcium oxalate dihydrate (COD). Urine apparently contains a determinant for COD formation. To identify the determinant, the effects of pH, temperature, oxalate, calcium, urate, citrate, magnesium, sulfate and chondroitin sulfates (CS) on calcium oxalate crystal formation were studied. Lower temperatures, higher oxalate concentrations and higher pH favored COD formation in a SU. Mixed CS in the presence of citrate were the most decisive determinant of COD formation. Substitution of CS for agar and gelatin produced similar results, indicating that the colloidal effect of the macromolecules determines COD formation. Identification of the determinants led to a simple, reproducible method of COD formation in SU without natural urine. Addition of strontium to SU resulted in dodecahedral bipyramids. Interpenetration twinning of bipyramids occur within seconds of the crystal formation.

Calcium Oxalate↗
PubMed1995

Signaling difference between class IgM and IgD antigen receptors.

Most mature B lymphocytes coexpress two classes of antigen receptor, IgM and IgD. The differences in the signal transduction from the two receptors are still a matter of controversy. We have analyzed B-cell lines expressing IgM or IgD antigen receptors with the same antigen specificity. Cross-linking of these receptors with either antigen or class-specific antibodies results in the activation of protein tyrosine kinases and the phosphorylation of the same substrate proteins. The kinetic and intensity of phosphorylation, however, was quite different between the two receptors when they were cross-linked by antigen. In membrane IgM-expressing cells, the substrate phosphorylation reached a maximum after one minute and diminished after 60 minutes, whereas in the membrane IgD-expressing cells, the substrate phosphorylation increased further over time, reaching its maximum at 60 minutes and persisting longer than 240 minutes after exposure to antigen. Recently prolonged signaling has been found to be responsible for signaling differences between tyrosine kinase receptors using otherwise similar signaling routes. Thus, the duration of a signal may be an important biological feature of signal-transducing cascades.

Amino Acid Sequence↗
PubMed1995

The B cell antigen receptor of class IgD induces a stronger and more prolonged protein tyrosine phosphorylation than that of class IgM.

Most mature B lymphocytes coexpress two classes of antigen receptor, immunoglobulin (Ig)M and IgD. The differences in the signal transduction from the two receptors are still a matter of controversy. We have analyzed B cell lines expressing IgM or IgD antigen receptors with the same antigen specificity. Cross-linking of these receptors with either antigen, or class-specific antibodies, results in the activation of protein tyrosine kinases and the phosphorylation of the same substrate proteins. The kinetic and the intensity of phosphorylation, however, was quite different between the two receptors when they were cross-linked by antigen. In membrane IgM-expressing cells, the substrate phosphorylation reached a maximum after 1 minute and diminished after 60 minutes whereas, in the membrane IgD-expressing cells, the substrate phosphorylation increased further over time, reached its maximum at 60 minutes, and persisted longer than 240 minutes after exposure to antigen. As a result, the intensity of protein tyrosine phosphorylation induced by cross-linking of membrane IgD was stronger than that induced by membrane IgM. Studies of chimeric receptors demonstrate that only the membrane-proximal C domain and/or the transmembrane part of membrane-bound IgD molecule is required for the long-lasting substrate phosphorylation. Together, these data suggest that the signal emission from the two receptors is controlled differently.

Antibodies, Anti-Idiotypic↗
PubMed1995

Function of B-cell antigen receptor of different classes.

Most mature B lymphocytes co-express two classes of antigen receptor, IgM and IgD. The differences in the signal transduction from the 2 receptors are still a matter of controversy. We have analysed B-cell lines expressing IgM or IgD antigen receptors with the same antigen specificity. Cross-linking of these receptors with either antigen or class-specific antibodies results in the activation of protein tyrosine kinases and the phosphorylation of the same substrate proteins. The kinetics and intensity of phosphorylation, however, were quite different between the 2 receptors when they were cross-linked by antigen. In membrane IgM-expressing cells, the substrate phosphorylation reached a maximum already after 1 min and diminished after 60 min whereas in the membrane IgD-expressing cells, the substrate phosphorylation increases further over time, reached its maximum at 60 min and persisted longer than 240 min after exposure to antigen. Recently prolonged signaling has been found to be responsible for signaling differences between tyrosine kinase receptors using otherwise similar signaling routes. Thus, the duration of a signal may be an important biological feature of signal transducing cascades.

Amino Acid Sequence↗
PubMed1995

G protein-coupled inward rectifier modulated by dopamine agonists in cultured substantia nigra neurons.

Dopamine release from dopaminergic neurons in the substantia nigra plays an important role in regulating their activity. In the present experiments the whole-cell clamp technique was used to elucidate the modulatory role of dopamine on K+ conductance in substantia nigra neurons in culture. In pars compacta neurons held near the resting potential, dopamine and quinpirole (a D2 receptor agonist) increased membrane conductance. This response was blocked by S(-)-sulpiride, a D2 receptor antagonist. The current-voltage relation of the quinpirole-induced current showed an inward rectification with a reversal potential that approximately equaled the K+ equilibrium potential. Intracellular application of a non-hydrolysable GTP analogue, guanosine 5'-O-(3-thiotriphosphate; 0.1-0.5 mM) into pars compacta neurons produced an initial spontaneous increase in an inwardly rectifying K+ conductance. Quinpirole markedly accelerated this conductance increase. In cells loaded with a poorly metabolized GDP analogue, guanosine 5'-O-(2-thiodiphosphate), the quinpirole response was diminished. Treatment of pars compacta neurons with pertussis toxin abolished the D2 response. Intracellular application of cyclic AMP (1 mM) neither mimicked nor occluded the D2 response. These results indicate that D2 receptor agonists produce neuronal inhibition by activating an inwardly rectifying K+ current, that this D2 agonist effect is mediated by a pertussis toxin-sensitive G protein, and that cyclic AMP does not mediate the D2 response. Unexpectedly, in cells loaded with guanosine 5'-O-(3-thiotriphosphate) after the inwardly rectifying K+ conductance spontaneously reached a maximum, it started to decline slowly. In cells loaded with guanosine 5'-O-(2-thiodiphosphate), the quinpirole response became diminished at first, but then the membrane conductance slowly increased, together with an increase in the quinpirole response. These results were explained by an interplay of two G proteins, one producing an increase and the other producing a decrease in the K+ conductance. In some pars reticulata neurons, R(+)-SKF-38393 (a D1 receptor agonist) reduced an inwardly rectifying K+ conductance; this would excite the neuron under current clamp conditions. The present study shows that cultured substantia nigra neurons produce functional responses to dopamine agonists. Using these neurons, the ionic mechanisms and signal transduction mechanisms of the responses were elucidated in a more critical manner than in previous studies.

Animals↗
PubMed1995

IgM-mediated B cell apoptosis.

Cross-linking of surface immunoglobulin M (sIgM) on normal mature B cells induces different signaling consequences, including DNA synthesis (positive signaling) and cell cycle arrest and/or death by apoptosis (negative signaling). Presumably, the difference depends on the intensity of sIgM cross-linking: relatively weak cross-linking induces DNA synthesis, moderate cross-linking induces DNA synthesis with cell cycle arrest at the G2/M interphase, and intense cross-linking induces apoptosis. In vivo experiments with transgenic mice have shown that relatively weak cross-linking of sIgM by soluble antigens induces anergy in autoreactive B cells, whereas intense sIgM cross-linking by membrane-bound forms of antigens induces deletion of them. However, it is still unknown whether the different intensities of sIgM cross-linking generate qualitatively different signals responsible for DNA synthesis or cell death or whether they generate qualitatively the same but quantitatively different signals, and the quantitative difference is responsible for the induction of positive or negative signaling. The sIgM-mediated negative signaling presumably plays an important role in the induction and maintenance of B cell tolerance, and sIgD and sIgG also possess the machinery necessary for negative signaling. Negative signaling through sIgM is dependent on tyrosine kinase(s) and Ca2+ influx and is sensitive to cyclosporin A in certain types of B cells but not in all B cells. It has been suggested that there are different intracellular signaling pathways that transduce negative signaling via sIgM, and that activation-induced B cell death by sIgM cross-linking does not necessarily show DNA fragmentation and the morphology of apoptosis. On the other hand, sIgM-mediated B cell death may be inhibited in the presence of appropriate co-stimulators such as IL-4, alpha-, and beta-interferons and CD40-mediated signaling. The CD40-mediated signaling effectively inhibits sIgM-mediated B cell apoptosis in many but not all experimental systems. Although homotypic cell adhesion through the LFA-1/ICAM-1 dependent pathway was shown to be involved in certain types of CD40-mediated inhibition of sIgM-mediated negative signaling, it is still not known how the cytokines and CD40-mediated signaling inhibit sIgM-mediated B cell death. The molecular mechanisms responsible for sIgM-mediated negative signaling and for the inhibitory signaling against sIgM-mediated negative signaling need further elucidation.

Animals↗
PubMed1995

Redistribution of facial nerve motor neurons after recovery from nerve crushing injury in the gerbil.

We investigated the redistribution of facial motor neurons after recovery from a crush injury of the facial nerve in the mongolian gerbil, with the retrograde transportation of horseradish peroxidase (HRP) technique. The facial nerve at the vertical segment was crushed unilaterally for 10 s with forceps. After 1 month, movement of the vibrissae and blinking reflex were observed. Three months after nerve injury, we obtained the brainstems to investigate the distribution of the facial nerve motor neurons. On the normal side, motor neurons of the ophthalmic branch of the facial nerve were organized at the dorsomedial and dorsolateral subdivisions of the facial nucleus, and those of the superior buccal branch were distributed at intermediate and ventrolateral subdivisions of the facial nucleus in the brainstem. On the experimental side, instead of somatotopical organization, we found widespread irregular distribution of the motor neurons of both branches in the entire facial nucleus of the brainstem.

Animals↗
PubMed1995

Expression of p53 and NDP-K/nm23 in gastric carcinomas--association with metastasis and clinicopathologic parameters.

To evaluate the role of p53 and NDP-K/nm23(nm23) protein as a prognostic factor and their relation to metastasis of cancer, we studied metastatic and nonmetastatic gastric carcinoma specimens by immunohistochemical staining. Among the 101 specimens examined, 37(36.6%) showed positivity in staining for p53 protein and 64(63.4%) showed no detectable p53 protein in tumor cells. p53 overexpression was correlated with depth of invasion, lymphatic invasion, lymph node metastasis and distant metastasis. Out of 101 specimens, 35 cases had no staining for nm23. 62 cases(61.4%) exhibited a cytoplasmic staining on most cells and 42 cases (41.6%) had nuclear staining. In 16 of 101 cases(15.8%), a mild to moderate membranous staining was observed in some cells. Cytoplasmic nm23 expression was negatively correlated with lymph node metastasis(P < 0.01) and distant metastasis(P < 0.01). The nuclear nm23 expression showed negative correlation with depth of invasion(P < 0.01), lymphatic invasion(P < 0.01), lymph node metastasis(P < 0.01), and distant metastasis(P < 0.04). The membranous nm23 expression revealed negative correlation with lymphatic invasion(P < 0.02), lymph node metastasis(P < 0.01) and distant metastasis(P < 0.02).

Adult↗
PubMed1995

Overexpression of a gene cluster encoding a chalcone synthase-like protein confers redbrown pigment production in Streptomyces griseus.

A 7.0-kb DNA fragment that conferred redbrown pigment production on Streptomyces griseus was shotgun-cloned with a multicopy vector pIJ486 from this microorganism. By restriction endonuclease mapping and subcloning, a 1.5-kb fragment which is essential for the production of redbrown pigment was determined. The nucleotide sequence of this region revealed the presence of two open reading frames, ORF1 with 109 amino acids (named RppA) and ORF2 with 262 amino acids (RppB), in addition to a truncated ORF3. The termination codon of rppA and the initiation codon of rppB overlapped, sharing one common nucleotide, which strongly suggests that these two genes are cotranscribed. Both rppA and rppB were essentially required for the pigmentation. The RppB protein showed great similarity in amino acid sequence to a chalcone synthase, a key enzyme of central importance in the biosynthetic pathway of all classes of flavonoids in plants. Part of RppA showed sequence similarity to the 33kDa phosphoprotein of adenovirus. Nucleotide sequences homologous to rppA and rppB were widely distributed in Streptomyces species, as determined by Southern hybridization. Further nucleotide sequencing of the entire orf-3 gene showed that ORF3 with 403 amino acids was a cytochrome P-450 (named P-450RPP). These data suggested that the cloned fragment contained part of a gene cluster for the biosynthesis of a certain metabolite. Introduction of the subcloned 1.5-kb fragment into Streptomyces lividans as well as Escherichia coli also caused production of redbrown pigment, suggesting that RppA and RppB are capable of synthesizing the redbrown pigment from metabolites commonly present in bacteria.

Acyltransferases↗
PubMed1995

Apoptosis and calcification.

Calcification in necrosis has long been known. Of the tissue components, the cells are most vulnerable. Nevertheless, little attention has been paid to the role of cell death in calcification. This review attempts to update the mechanism of calcification with an emphasis on the role of apoptosis in calcification. A brief review on the basic sciences relevant to calcification is followed by a discussion of abnormal Ca2+ and Pi homeostasis in cell injury and apoptosis. Concomitant increases in Ca2+ and Pi in blebs (and matrix vesicles) formed by apoptotic and/or necrotic cells are apparently the primary mechanism of calcification. In addition, membranous cellular degradation products (CDP) resulting from cell disintegration in toto frequently serve as the nidus of calcification. Published data on physiological calcification are compared with findings in various dystrophic calcinoses. This led to the conclusion that apoptosis most likely underlies the mechanism of both physiological and pathological calcifications. It is concluded that calcification is an important function of apoptosis. The mechanism of calcification by CDP and morphology of the resultant calcific deposits are complex.

Adenosine Triphosphate↗
PubMed1994

The IgM antigen receptor of B lymphocytes is associated with prohibitin and a prohibitin-related protein.

The two major classes of antigen receptors on murine B lymphocytes, mIgM and mIgD, are both contained in a complex with two additional molecules, Ig-alpha and Ig-beta, which permit signal transduction. Accordingly, early biochemical events after antigen binding to either receptor are similar; biological effects, however, are different. Here, we describe three newly discovered intracellular proteins of 32, 37 and 41 kDa molecular mass, that are non-covalently associated with mIgM, but not with mIgD. These proteins coprecipitate with mIgM in Triton X-100 and Nonidet P-40, but not in digitonin lysates. In addition, mIgM is to some extent associated with 29 and 31 kDa proteins that are predominantly associated with mIgD (see accompanying paper). Amino acid sequencing of p32 and p37 identified p32 as mouse prohibitin; this was corroborated by Western blot analysis with antibodies specific for rat prohibitin. p37 is a newly discovered protein. cDNA clones for both proteins were isolated and sequenced. The deduced amino acid sequence of p32 is identical to that of rat prohibitin. p37 is highly homologous to p32. Since prohibitin was identified as an inhibitor of cell proliferation, its association with mIgM, but not mIgD, could explain the different biological events elicited after engagement of each receptor.

Amino Acid Sequence↗
PubMed1994

Two new proteins preferentially associated with membrane immunoglobulin D.

The IgM and IgD classes of antigen receptor can perform different functions on B cells. However, so far no class-specific components communicating with the cytoplasm have been found in the two antigen receptors. We have employed a new biotinylation protocol to search for intracellular membrane Ig-associated proteins. Here we describe two proteins of 29 and 31 kDa that are associated with membrane IgD and to some extent with membrane IgM. The membrane IgM molecule is associated specifically with three proteins of 32, 37 and 41 kDa. The purification and sequencing of the two mIgD-associated proteins revealed that they are novel proteins which are related to each other. These proteins may be the missing link between the antigen receptor and the cytoskeleton and may contribute to functional differences between membrane IgM and membrane IgD.

Amino Acid Sequence↗
PubMed1994

Annexin-I inhibits phospholipase A2 by specific interaction, not by substrate depletion.

Annexin-I is a calcium dependent phospholipid binding and phospholipase A2 (PLA2) inhibitory protein. A 'substrate depletion' model has been proposed for the mechanism of PLA2 inhibition by annexin-I in studies with 14 to 18 kDa PLA2s. Herein, we have studied the inhibition mechanism using 100 kDa cytosolic PLA2 from porcine spleen. The inhibition has been measured at various substrate and calcium ion concentrations. The pattern of PLA2 inhibition by annexin-I was consistent with a 'specific interaction' mechanism rather than the 'substrate depletion' model. Apparent contraction with previous studies can be explained by the calcium-dependent binding of annexin-I to the substrate.

Animals↗
PubMed1994

Synthesis, structure, and antitumor activity of 1,3-dithiol- and 1,3-dithiolan-2-ylidenemalonatoplatinum(II) complexes.

1,3-Dithiol- and 1,3-dithiolan-2-ylidenemalonatoplatinum(II) complexes A2Pt(OOC)2C = CR2 (A = NH3, cyclopropylamine (CPA) or A2 = ethylenediamine(EDA), trans(+/-)-1,2-diaminocyclohexane(DACH); R2 = -SCH = CHS-, -SCH2CH2S-) have been synthesized and subjected to in vivo assay for antitumor activity after characterization by means of elemental analysis, IR spectroscopy, and x-ray analysis. The molecular structure of (CPA)2Pt(OOC)2C = CSCH = CHS has been determined by x-ray diffraction: space group P2(1)/n, a = 7.955(1), b = 16.912(2), c = 15.116(2) A, beta = 102.74(1) degrees, z = 4, R = 0.032, Rw = 0.035. Among the Pt(II) complexes studied, biscyclopropylamineplatinum(II) complexes both of the above-mentioned dicarboxylate leaving groups exhibited much higher antitumor activity against the leukemia L1210 cell line compared with the known cisplatin.

Animals↗