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Y T Kim

Publications and source records attributed to Y T Kim.

At least 127 records · Page 7Linked to original sources
PubMed1991

"Cross-wiring" of the immune response in old mice: increased autoantibody response despite reduced antibody response to nominal antigen.

Older humans and experimental animals have been repeatedly found to have higher titers of autoantibodies than do younger individuals despite the impaired responses of older individuals to foreign antigens. The studies reported here were designed to examine the relationship between these two age-related changes in antibody responses. Antibody response to foreign antigen was measured concurrently with autoantibody response in the same mice. Old mice (18-24 months old) had decreased responses to foreign antigens and increased responses to bromelain-treated syngeneic erythrocytes, compared to young mice (2 months old). In vitro mixing experiments were consistent with the possibility that suppressor cell activity in spleen cells from old mice reduce the antibody response to foreign antigen but not to autologous antigen. The results support an emerging view that age-associated changes in immune responses are the result of dysregulation rather than exhaustion of the immune system.

Aging↗
PubMed1991

Role of induction chemotherapy in invasive cervical cancer.

The 386 cases of invasive cervical carcinoma treated with radiotherapy alone were statistically analyzed to delineate the high risk factors (HRFs) associated with a significantly high treatment failure rate; they were (1) stages III-IV, (2) lesion greater than or equal to 4.0 cm, (3) small cell carcinoma or adenocarcinoma, (4) stages I-II with lesion greater than or equal to 4.0 cm, and (5) lymphographic evidence of nodal metastasis. Then, chemoradiotherapy (induction chemotherapy plus subsequent radiotherapy) was instituted to 113 invasive cervical carcinoma patients with at least one such HRF. Each patient received two to three cycles of induction chemotherapy at about 3-week intervals. For squamous cell carcinoma, cisplatin, 100 mg/m2 iv, was followed immediately by 5-fluorouracil, 1000 mg/m2, as a 24-hr iv infusion x 5 days. For adenocarcinoma, cisplatin, 70 mg/m2 iv, on Day 1 was followed by cytoxan, 250 mg/m2, on Day 2, and adriamycin, 45 mg/m2, on Day 3. Five-year survival of these patients according to each HRF, in the above order, was 69.1, 67.2, 68.1, 78.3, and 79.5% after chemoradiotherapy, all significantly higher than 57.4, 53.0, 54.5, 48.0, and 48.8% by radiotherapy alone. Drug toxicities such as leukopenia, hepatotoxicity, nephrotoxicity, and hypomagnesemia were seen in 46.5, 53.2, 47.1, and 55.4% of all cycles, respectively. The toxicities altered drug schedule in 191 (61.2%) ongoing induction chemotherapy cycles. Our cisplatin-based induction chemotherapy is considered an effective preradiotherapy adjunct that can reduce treatment failure in HRF-associated invasive cervical carcinoma.

Adenocarcinoma↗
PubMed1991

The efficacy of script contexts in language comprehension intervention with children who have mental retardation.

This study was designed to investigate the effects of script-based and nonscript-based treatment on the language comprehension of 4 preschool children with mental retardation. An alternating treatments design (ATD) in combination with a multiple baseline design was used to evaluate treatment effects. Treatments were comprised of three script routines and three nonscript activities. Two semantic constructions were selected for training and counterbalanced across subjects and treatments. Daily probes were administered to assess the effects of the treatments. The script-based treatment was more effective than the nonscript treatment in facilitating comprehension of the targeted semantic constructions in 3 of the 4 subjects.

Adolescent↗
PubMed1990

Cellular basis for the age-associated increase in autoimmune reactions.

The mechanisms that lead to the increased expression of autoantibodies with age are poorly understood. We have studied the number, size, and density of spleen and peritoneal cells from young and old BALB/c and C57BL/6 mice as well as the frequency of clonal precursors for antibodies to mouse erythrocytes, thyroglobulin, and IgG in these lymphoid preparations. Old mice have a 6-fold increase in the number of resident peritoneal cells and a 2-fold increase in the absolute number of Ly1-bearing B cells in this population. Furthermore, old mice have twice as many large, low density splenic B cells as young mice. The frequencies of B cell clonal precursors for anti-BrMRBC and anti-thyroglobulin antibody-forming cells in old mice were 3-10 times greater than in young mice. In the same cultures, however, no increase in the frequencies of B cell clonal precursors for anti-IgG or anti-DNA antibody forming cells was detected in old compared to young mice. These findings and other data suggest that there are at least two families of B cell autoantibody precursors, one including anti-BrMRBC and anti-thyroglobulin autoantibodies, the other including anti-IgG and anti-DNA antibodies. Studies of the differential regulation of these two families of autoantibody precursors might contribute to a greater understanding of autoimmune phenomena in age and disease.

Aging↗
PubMed1990

Pyridoxal kinase. Structure and function.

Chymotryptic digestion of sheep brain pyridoxal kinase, a dimer of identical subunits each of 40 kDa, yields two fragments of 24 and 16 kDa with concomitant loss of catalytic activity. These fragments were separated by HPLC and used for binding studies with ATP and pyridoxal analogues. The spectroscopic properties of trinitrophenyl-ATP bound to the 24-kDa fragment are indistinguishable from those of TNP-ATP bound to the native kinase. The small 16-kDa fragment, generated by proteolytic cleavage of the kinase, does not bind any of the analogues. The same pattern of digestion was observed when IAF pyridoxal kinase, carrying a fluorescent probe covalently bound to a specific SH residue, was preincubated with chymotrypsin. The kinetics of proteolysis of IAF-pyridoxal kinase was monitored by emission anisotropy, and the analysis of the initial rate of proteolysis at various concentrations of chymotrypsin reveals that the rate of unfolding of native pyridoxal kinase plays a dominant role in the proteolytic process.

Adenosine Triphosphate↗
PubMed1990

Allelic interactions at the shibire locus of Drosophila: effects on behavior.

This report describes a detailed behavioral study of four shi alleles, shits1, shits2, shits4, and shiST139, and their heteroallelic combinations. Flies of different heteroallelic combinations (shi/shi) were less sensitive to high temperature than the corresponding homozygotes. Among them, shits2/shits4 showed a striking reduction in temperature sensitivity. In contrast, different shi/+ heterozygotes were more severe in temperature sensitivity than the hemizygotes, Df/+. The hemizygous combinations of shi alleles over deficiency (shi/Df) were not completely lethal, with shits2 conferring distinctively higher and shits4 lower viability. A novel behavior, bang sensitivity, was also found in shi/Df. The results of allelic interactions suggest that the shi mutations examined appear to be antimorphic and that the shi gene products are likely to function in multimeric form.

Alleles↗
PubMed1990

Reversible inhibition of endocytosis in cultured neurons from the Drosophila temperature-sensitive mutant shibirets1.

The Drosophila mutant, shibirets1 (shits1), is paralyzed at restrictive temperatures (greater than 29 degrees C) by a reversible block in synaptic transmission. Heat pulses deplete synaptic vesicles in nerve terminals and inhibit endocytic internalization of plasma membrane in garland cells and oocytes. In dissociated cultures of larval central nervous system (CNS), a temperature-sensitive defect is also expressed in shits1 neurons: at 30 degrees C, growth cone formation is retarded and neurite outgrowth is arrested. We now report that we have examined constitutive endocytosis in Drosophila CNS culture and have demonstrated directly an endocytic defect in shits1 neurons. At the permissive temperature, 20-22 degrees C, both shits1 and wild-type neurons actively endocytosed fluorescein-labelled dextran (40 KD, 5%) or horseradish peroxidase (HRP, 1%). Within 5 min, HRP was seen in vesicles, cup-shaped bodies, tubules and multivesicular bodies in neurites and cell bodies. In contrast, endocytosis was inhibited in cultures derived from the temperature-sensitive paralytic shits1 by a 15 min heat pulse (30 degrees C). Even after 30 min of HRP exposure at 30 degrees C, HRP-containing membranes were absent from almost all shits1 neurites; a minority of cell bodies had a few HRP-containing vesicles. The temperature-dependent block in endocytosis was readily reversed at 20 degrees C. Interestingly, the block was overcome by high concentration of external cations: shits1 neurons in culture actively took up HRP in numerous vesicles at 30 degrees C if 18 mM Ca2+ or Mg2+ was added to the medium. Our results support the notion that membrane recycling plays a critical role in regulating neurite outgrowth. This study also provides baseline information for further mutational analysis of the mechanism underlying the membrane cycling process in cultured neurons.

Animals↗
PubMed1990

Immunobiology of aging and cancer.

Although the incidence of neoplasms is increased in the elderly, some tumors appear to grow more slowly in old as compared to young patients. We have used the B16 melanoma to explore the relationship between age, T-lymphocyte function, and the rate of tumor growth. Increasing age is associated with a decreased rate of tumor growth and impaired T-cell function in C57BL/6 mice. Furthermore, when T-cell immunity in young mice is compromised by thymectomy, B16 tumor growth is decreased. Mixed cell transfer studies demonstrated that T cells from young but not old donors stimulate the growth of B16 melanoma cells in young lethally irradiated recipients. Recently, T cells from young but not old mice have been reported to produce angiogenic factors. As tumors from young mice have a richer vascular supply than in old mice, it appears that one mechanism for the age-associated decrease in B16 melanoma growth is the decreased capacity of T cells from old mice to generate angiogenic factors. However, parabiosis of young and old mice showed that local factors in old mice also limit the stimulatory influences of T cells from young mice. Novel therapeutic approaches to limit the growth of tumors might result from a greater understanding of the production of and response to angiogenic factors produced by T cells.

Aging↗
PubMed1989

Activation of a flavoprotein by proteolysis.

Chymotryptic digestion of brain pyridoxine-5-P oxidase brings about a 4-fold enhancement of the catalytic power (Vmax/KM) using pyridoxine-5-P as substrate in the assay mixtures. The chymotrypsin-treated enzyme is less susceptible to inhibition by pyridoxal-5-P than the native enzyme. Fragments arising from limited proteolysis were separated by affinity chromatography using P-pyridoxal-Sepharose as supporting matrix. Catalytically active fractions, eluted by pyridoxine-5-P (5mM), displayed three bands when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular masses of the three protein bands are considerably lower than 28 kDa, the molecular mass of monomeric pyridoxine-5-P oxidase. Spectroscopic studies, absorption, fluorescence, and circular dichroism revealed that the microenvironment surrounding the cofactor flavin mononucleotide is not perturbed by limited proteolysis.

Animals↗
PubMed1989

Sequence of the cysteinyl-containing peptides of 4-aminobutyrate aminotransferase. Identification of sulfhydryl residues involved in intersubunit linkage.

Three cysteine-containing tryptic peptides were isolated and sequenced from mitochondrial 4-aminobutyrate aminotransferase using DABIA (4-dimethylaminoazobenzene-4-iodoacetamide) as specific labeling reagent for sulfhydryl groups. The enzyme is a dimer made up of two identical subunits, but four out of the six cysteinyl residues/dimer form disulfide bonds when treated with iodosobenzoate to yield inactive enzyme species. To identify the cysteinyl residues undergoing reversible oxidation/reduction, the S-DABIA-labeling patterns of the fully reduced (active) and fully oxidized (inactive) forms of the enzyme were compared. Tryptic digests of the reduced enzyme contained three labeled peptides. If the enzyme was treated with iodosobenzoate prior to reaction with DABIA and tryptic digestion, only one labeled peptide was detected and identified (peptide I), indicating that the two missing cysteinyl-containing peptides (peptides II, III) have been oxidized. The sulfhydryl groups undergoing oxidation/reduction were found to be intersubunit, based on SDS/polyacrylamide gel electrophoresis results. The loss of catalytic activity of 4-aminobutyrate aminotransferase by oxidation of sulfhydryl residues is related to constraints imposed at the subunit interface by the insertion of disulfide bonds.

4-Aminobutyrate Transaminase↗
PubMed1989

The influence of immune complexes, steric effects, and antigen-antigen interactions on the sensitivity of enzyme-linked immunosorbent assays.

Serum from mice hyperimmunized with 2,4,6-trinitrophenylated bovine gamma globulin (TNP-BGG) or keyhole limpet hemocyanin have been shown to have enhanced binding to several ligands unrelated to the antigen used for immunization. Addition of the immunizing antigen to the serum can result in increased binding to unrelated ligands and to the polyvinyl chloride surface of microtiter wells in solid-phase enzyme-linked immunosorbent assays. In a competitive binding assay using TNP-BGG-hyperimmune serum adsorbed to the microtiter well followed by an alkaline phosphatase conjugate of BGG in the presence or absence of TNP-BSA, substantial inhibition of BGG binding is seen. Steric hindrance appears to be the major cause of such inhibition since addition of hapten alone has little effect on BGG binding. An antigen-antigen interaction between KLH and TNP is also detectable. Immune complex formation, steric effects, and antigen-antigen interactions potentially have substantial influences on ELISA sensitivity and must be considered as possible sources of artifact in these assays.

Animals↗
PubMed1989

Serum copper concentration as an index of clinical lung injury.

The purpose of this ongoing study is to determine whether thoracic radiotherapy for lung cancer produces an early increase in serum copper (Cu) concentration, an increase which might predict clinical outcome. Copper and iron concentrations were measured in serum obtained from nonsmall cell lung cancer patients at 0, 1, 2, 4, and 6 weeks after the start of radiotherapy. Control groups included patients irradiated for breast cancer (low dose of radiation to the lung), for endometrial, cervical or prostatic cancer (no dose to lung), and patients with congestive heart failure, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and cutaneous burns with or without smoke inhalation (no irradiation). Serum Cu concentration increased at least 10 micrograms/dl from the pretreatment level in approximately 75% of the adenocarcinoma and squamous cell lung cancer patients, but in only 1 of 4 undifferentiated lung cancer cases. In virtually all of these responders, serum Cu increased to a maximum at 2 weeks after the start of therapy, then plateaued or decreased slightly despite continuing irradiation. Within the subset of squamous cell lung cancers, there was a direct correlation between the degree of histologic differentiation and both baseline serum Cu concentration and the probability of an early increase therein. In contrast, only 33% of breast cancer patients and 15% of endometrial, cervical and prostate cancer patients exhibited an increase in serum Cu concentration at 2 weeks after the start of radiotherapy. Serum Cu concentration was within normal limits in virtually all patients with congestive heart failure, pulmonary hypertension, and COPD. Burn patients exhibited a significant reduction in serum Cu, although concomitant smoke inhalation increased serum Cu back to low-normal levels. Serum iron concentration did not change significantly in any category of patients. These data suggest that thoracic radiotherapy for well differentiated non-small cell lung cancer is accompanied by an early increase in serum Cu concentration. This increase is partly but not wholly related to lung dose in particular rather than tissue dose in general, and specifically reflects radiation-induced lung injury rather than pneumopathy in general. In lung cancer patients, the change in serum Cu concentration during the first 2 weeks of radiotherapy exhibits a sufficiently broad range (+60 to -13 micrograms/dl) to permit testing this parameter as a predictor of tumor response and pulmonary complications.

Adenocarcinoma↗
PubMed1989

Immunological studies of aging. Normal B-cell repertoire in aged mice: studies at a clonal level.

As previously reported, old mice produce lower avidity plaque-forming cells (PFC) after immunization with 2,4,6-trinitrophenyl-Ficoll (TNP-F) than do young mice. However, if spleen cells from TNP-F-immunized old mice are incubated with hapten to elute auto-anti-idiotype antibody then high avidity PFC, comparable to those in young mice, are detected. To further evaluate the effect of age on the B-cell repertoire anti-2,4,6-trinitrophenyl-bovine gamma globulin (TNP-BGG) hybridomas were prepared from young (6 to 8 weeks old) and old (18 to 24 months old) mice which had been primed and boosted with TNP-BGG. The monoclonal antibodies (MoAb's) were TNP-specific. Spleens from old and young mice were comparable with respect to the incidence of immunoglobulin-secreting hybridomas obtained, the incidence of TNP-BGG-specific hybridomas obtained, and the isotype distribution of the anti-TNP-BGG hybridomas. The avidities for TNP-BGG of the IgG1 anti-TNP-BGG MoAb's obtained from old and young donors were also comparable. The overall results thus suggest that old and young mice have similar B-cell repertoires and that differences in the antibodies produced are due to regulatory influences.

Aging↗
PubMed1989

Deficiency of pyruvate dehydrogenase complex (PDHC) in Leigh's disease fibroblasts: an abnormality in lipoamide dehydrogenase affecting PDHC activation.

Several groups have reported abnormalities of the pyruvate dehydrogenase complex (PDHC) in cultured cells or other tissues from patients with Leigh's disease (subacute necrotizing encephalomyelopathy). We therefore undertook studies to elucidate the molecular basis of the defect of PDHC in cultured skin fibroblasts from two patients with Leigh's disease. The deficit of total PDHC activity in homogenates of Leigh's disease fibroblasts could be restored by adding exogenous lipoamide dehydrogenase (LAD, E3), the third component of PDHC. The LAD in these Leigh's disease cells had a markedly reduced ability (less than 20% of normal LAD) to reconstitute with other PDHC components to form active enzyme complex. A polyclonal antibody to pig heart LAD inhibited LAD activity in control cells more efficiently than in Leigh's disease cells. Other mitochondrial enzyme activities and growth of these two Leigh's disease cells appeared normal. These results suggest that the deficiency of PDHC in these two patients with Leigh's disease was due to a structural abnormality of the LAD component of PDHC.

Brain Diseases, Metabolic↗
PubMed1989

Structure-function analysis of angiotensin-converting enzyme inhibitors as modifiers of radiation-induced pulmonary endothelial dysfunction in rats.

We have previously demonstrated that thiol-containing collagen antagonists (penicillamine) and angiotensin-converting enzyme (ACE) inhibitors (Captopril and CL242817) ameliorate endothelial dysfunction in irradiated rat lung. The purpose of the present study was to determine whether the non-thiol ACE inhibitor CGS13945 also modifies radiation-induced pulmonary endothelial dysfunction in rats sacrificed 2 months after a single dose (0-30 Gy) of 60 Co gamma rays to the right hemithorax. The CGS13945 was administered in the feed continuously after irradiation at a regimen of 30 mg (kg body weight)-1 day-1. Four markers of lung endothelial function were monitored: ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Right lung ACE and PLA activities decreased with increasing radiation dose, and CGS13945 significantly ameliorated both responses. Dose-reduction factors (DRF) for the inhibitor were 1.80 for ACE activity and 1.41 for PLA activity (p less than 0.05). In contrast, lung PGI2 and TXA2 production increased with increasing radiation dose, and CGS13945 did not influence either response significantly. Thus the ACE inhibitor CGS13945 modifies radiation-induced pulmonary endothelial dysfunction in rats, indicating that the presence of a thiol group is not essential for therapeutic efficacy in this class of compounds. On the other hand, CGS13945 exhibits a differential sparing of radiation-induced pulmonary endothelial dysfunction, as does penicillamine. A structure-function analysis of the present and previous data indicates that all of the ACE inhibitors tested (Captopril, CL242817 and CGS13945) spare the radiation-induced suppression in lung ACE and PLA activity; all of the thiol compounds tested (penicillamine, Captopril and CL242817) spare the radiation-induced elevation in lung PGI2 and TXA2 production; and the thiol ACE inhibitors (Captopril and CL242817) spare all four endothelial responses. These data confirm a novel and potentially important application for ACE inhibitors as modifiers of radiation-induced lung injury, and suggest that there are at least two components to their mechanism of therapeutic action in this model.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Effects of symbolic play intervention with children who have mental retardation.

The effects of intervention versus nonintervention on the length and diversity of symbolic behaviors in children with mental retardation (classified as trainable) were compared. Eight children were matched on several variables and divided into two groups. The experimental, intervention group received 10 therapy sessions that were focused on symbolic play development; the control, nonintervention group did not receive play intervention. Children in the experimental group demonstrated qualitative as well as quantitative changes in their symbolic play profile. Clinical implications of these findings were discussed.

Animals↗
PubMed1989

Production of auto-anti-idiotype antibody during the normal immune response. XIV. Evidence for the antigen-independent operation of the idiotype network.

We have previously shown that that idiotype (Id) repertoire expressed by old mice is different from that of young mice after immunization with trinitrophenylated Ficoll. Older mice also produce more auto-anti-Id antibodies than do young mice. Mice surviving a normally lethal dose of radiation (800 rads) as result of partial shielding of their bone marrow slowly recover immune function, after the repopulation of their peripheral lymphoid system by bone marrow precursor cells. Aged mice subjected to such a procedure produce low auto-anti-Id responses, like those of young mice. However, transfer of splenic T cells from old donors into such mice increases the magnitude of the auto-anti-Id response. In the present studies, we show that the age-related shift in Id expression is also determined by the age of the donor T cells. Furthermore, we show in serial cell transfer studies that the peripheral T-cell population of old mice modifies the level of the auto-anti-Id response in the absence of antigen. The results thus provide evidence for the normal, in vivo, operation of an Id-anti-Id network between B and T lymphocytes.

Aging↗