Biomedical subjects

S K Kim

Publications and source records attributed to S K Kim.

At least 19 recordsLinked to original sources

PubMed1992

Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2.

Programmed cell death is a physiological process that eliminates unwanted cells. The bcl-2 gene regulates programmed cell death in mammalian cells, but the way it functions is not known. Expression of the human bcl-2 gene in the nematode Caenorhabditis elegans reduced the number of programmed cell deaths, suggesting that the mechanism of programmed cell death controlled by bcl-2 in humans is the same as that in nematodes.

Animals↗

PubMed1992

Loss of mitochondrial respiratory function and its suppression during cold ischemic preservation of rat livers with University of Wisconsin solution.

Preservation of the liver involves a period of cold (0 degrees to 4 degrees C) ischemia; the longer the ischemic period, the greater the injury to the liver. The mechanisms for cold-induced ischemic injury are not known, but it is clear that after preservation the liver has a reduced capacity to regenerate high-energy phosphate compounds (ATP). One cause for the delayed rate of ATP synthesis could be injury to the mitochondria. The effects of long-term (more than 24 hr) preservation on liver mitochondrial function have not been previously studied. In this study, rat livers were preserved in University of Wisconsin solution at 4 degrees C for up to 96 hr. After preservation, mitochondrial respiratory function was assayed in a homogenate and in isolated mitochondria. We saw a progressive increase in oligomycin-sensitive respiration with time of preservation (from 1.2 +/- 0.09 mumol.min-1.gm tissue-1 at 0 hr to 3.8 +/- 0.2 mumol.min-1.gm tissue-1 after 96 hr). The increase after 24-hr preservation (2.1 +/- 0.2 mumol.min-1.gm tissue-1) was also significantly greater than 0 time values (p less than 0.05). No decrease was found in uncoupler-stimulated respiration for up to 48 hr of preservation; only a small decrease was seen after 72 hr of preservation (about 30%). The cause of the increase in oligomycin-sensitive respiration appeared to be related to free fatty acids (or another uncoupling factor) generated during preservation. This was suggested from the fact that bovine serum albumin prevented the increase in oligomycin-sensitive respiration after all periods of preservation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1992

Oxidative interactions of cholesterol in the milk fat globule membrane.

The effects of oxidative interactions between cholesterol and milk fat globule membrane (MFGM) components, i.e., nonlipid fraction, total lipid, nonpolar lipid and polar lipid, on cholesterol oxidation were studied in the presence and absence of water. In the dry state, cholesterol natively present in MFGM appeared to be protected at 135 degrees C. The nonpolar lipid and nonlipid fraction contributed to the protective effect of MFGM. Added cholesterol accelerated the oxidation of membrane lipid fractions. At 75 degrees C, pure cholesterol and membrane lipid fractions did not show significant interaction. However, cholesterol and other lipids in MFGM were less stable than when these were heated separately. When cholesterol and membrane lipids were mixed in an aqueous medium at 75 degrees C, each accelerated the oxidation of the other. The MFGM exhibited a high protective effect on cholesterol oxidation in an aqueous environment. The nonlipid fraction protected cholesterol against oxidation, whereas the lipid fraction was destructive. In the absence of water, the net balance between these two opposing factors was destructive. The presence of water reversed the balance in favor of protection.

Animals↗

PubMed1992

Amylase mRNA synthesis and ageing in rat parotid glands following isoproterenol-stimulated secretion.

In the parotid, as well as in other exocrine glands, secretory protein synthesis declines with age. However, whether this decline in the steady-state rate of protein synthesis reflects the reduced digestive activity of the animal or actual cellular alterations that affect synthesis is unknown. Here the ability to synthesize amylase and its mRNA during the period of enhanced protein synthesis following secretion induced by isoproterenol was compared in acinar cells of 2-and 24-month-old rats. In unstimulated glands, rates of synthesis of total protein and amylase, as well as amounts of amylase mRNA, were significantly less in the older rats than in their younger counterparts. After stimulation with isoproterenol, which induced the secretion of about 50% of stored proteins, rates of synthesis of total protein, as well as amylase, were increased by about 2.5 x the unstimulated rates in both age groups. However, the amount of amylase mRNA did not increase in parallel with the increase in the rate of amylase protein synthesis in both young and old rats. The molecular size of the mRNA was the same in stimulated and unstimulated glands of both age groups. Thus, it appears that parotid acinar cells from old rats can be stimulated to synthesize secretory proteins at an increased rate. It remains to be determined what causes the reduced rate of protein synthesis in unstimulated glands in old rats.

Aging↗

PubMed1992

Dynamics of benzo[a]pyrene diol epoxide adducts in poly(dG-dC).(dG-dC) studied by synchrotron excited fluorescence polarization anisotropy decay.

Time-resolved fluorescence studies have been performed on (+)-anti-7,8-dihydrodiol-9,10-epoxybenzo[a]pyrene adducts in double-stranded poly(dG-dC).(dG-dC). Part of the adduct population gives rise to excimer fluorescence. The heterogeneous fluorescence emission decay curves at 22 degrees C could be resolved into three components with lifetimes: 0.4 ns, 3 ns and 24 ns for the total fluorescence (monomer and excimer emission), and 0.5 ns, 5 ns and 24 ns, respectively, for excimer emission alone. The relative amplitudes for the longer lifetimes were larger for the pure excimer population than for the mixed population. The fluorescence polarization anisotropy decay curves were resolved into two components of rotational correlation times: 0.4 ns and 25 ns for the total fluorescence and 0.3 ns and 33 ns for the excimer fluorescence. We interpret the two rotational correlation times to correspond to local motion of the adduct and segmental motion of the polynucleotide, respectively.

Chemical Phenomena↗

PubMed1992

Identification and quantitative detection of isomeric benzo[a]pyrene diolepoxide--DNA adducts by low-temperature conventional fluorescence methods.

The pyrene-like fluorescence of adducts derived from the covalent binding of (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [+/-]-anti-BPDE] to DNA increases in intensity by factors of 20 or more as the temperature is lowered from ambient to approximately 100 K. This effect is primarily associated with the strong quenching of the pyrene-like fluorescence of BPDE-deoxyguanosyl adducts at room temperature, and the suppression of the electron-transfer quenching mechanism at 100 K. In contrast, the fluorescence of BPDE-deoxyadenosyl adducts is not quenched at ambient temperatures, and the fluorescence yields of (+/-)-anti-BPDE-poly(dA-dT).(dA-dT) adducts increases by only a factor of 2 in this same temperature range. Utilizing an internal fluorescein fluorescence standard to correct for differences in light scattering and variations in instrumental factors, a fluorescence method is described for quantitatively determining the levels of benzo[a]pyrene diolepoxide derivatives covalently bound to cellular DNA at 100 K. The method is illustrated with (+/-)-reverse-BPDE [(+/-)-trans-9,10-dihydroxy-anti-7, 8-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene]. Adduct levels as low as 10 pmol in a 400 microliters sample volume can be detected and identified from their excitation and fluorescence emission spectra using a conventional and commercially available fluorometer. In the case of modified DNA extracted from BPDE-treated Chinese hamster ovary cells or from mouse skin (approximately 1 BPDE residue/20,000 bases), such an analysis requires only 100 micrograms of DNA. Conformationally different adducts derived from the binding of the isomeric (+/-)-anti-BPDE, (+/-)-reverse-BPDE or (+/-)-syn-BPDE to cellular DNA can be distinguished by their low-temperature fluorescence excitation spectra. Specifically, the quasi-intercalated site I BPDE adducts (believed to be associated with cis-addition stereochemistry) can be distinguished from site II adducts situated at external BPDE binding sites (trans-addition stereochemistry). These results suggest that the fates of these conformationally different BPDE-DNA adducts, e.g. due to enzymatic repair, can be monitored as a function of time in DNA extracted from intact, functioning cells.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1992

Combination of 5-fluorouracil and recombinant interferon alpha-2B in advanced gastric cancer. A phase I study.

Based on recent preclinical data suggesting synergism between 5-fluorouracil (5-FU) and interferon alpha (IFN-alpha) and clinical activity of the combination therapy in colon cancer, 14 patients with advanced gastric cancer were treated with combination therapy of 5-FU and recombinant interferon alpha-2b (rIFN alpha-2b) (Intron A, Schering, Kenilworth, NJ, U.S.A.). The maximum tolerated dose was 5-FU 750 mg/m2/day given as a continuous infusion daily for 5 days followed by weekly bolus injection of the same initial daily dose, plus rIFN alpha-2b 5 X 10(6) U given subcutaneously 3 times weekly starting day 1 of 5-FU infusion. The dose-limiting toxicities were fatigue/weakness, diarrhea, and neurologic toxicities such as somnolence and confusion. The other common side effects were nausea, fever, leukocytopenia, thrombocytopenia, and the darkening of the skin. Of 13 evaluable patients, 4 had a partial response (duration 6, 14, 24, and 28 weeks). These data suggest that combination therapy of 5-FU plus rIFN alpha-2b is tolerable and has manageable side effects in patients with advanced gastric cancer. Further Phase II study will be needed to define the antitumor activity of this combination.

Adult↗

PubMed1992

Replication of a mutant hepatitis B virus with a fused X-C reading frame in hepatoma cells.

We have previously described a mutant hepatitis B virus (HBV) with a fused X-C open reading frame (ORF) resulting from a single nucleotide insertion in the X-C overlapping region. A stably transformed cell line producing HBV particles, HepG2-K8, was established by transfecting the human hepatoma cell line HepG2 with a plasmid carrying four tandem repeats of the mutant HBV genome. The virus particles secreted into the culture medium were characterized by density gradient centrifugation and electron microscopy. The particles, similar to Dane particles by morphology and density, contained the mature HBV genome and endogenous DNA polymerase activity. Six HBV-specific transcripts of 4.0, 3.5, 2.2, 2.1, 1.2 and 0.9 kb were detected in HepG2-K8 cells by Northern blot analysis. cDNA cloning and sequence analysis of X mRNA showed that an elongated X ORF encoding 193 amino acids was created by a frameshift mutation in the 3'-terminal region of the wild-type X ORF and that the formation of an in-frame termination codon (TAA) resulted from polyadenylation. This elongated X gene product exerted transcriptional trans-activation.

Amino Acid Sequence↗

PubMed1992

Production of monoclonal antibody to a phenolic glycolipid of Mycobacterium tuberculosis and its use in detection of the antigen in clinical isolates.

A monoclonal antibody (MAbIII604) specific to phenolic glycolipid Tb (PGL-Tb), a Mycobacterium tuberculosis-specific antigen, was produced and used in the detection of the antigen. MAbIII604 reacted with the PGL-Tb antigen but not with other phenolic glycolipids from Mycobacterium leprae, M. bovis, and M. kansasii, thus indicating the specificity of the monoclonal antibody to PGL-Tb. A dot enzyme-linked immunosorbent assay with MAbIII604 was employed to detect the PGL-Tb antigen in lipids purified from M. tuberculosis clinical isolates. Of 50 isolates, 32 (64.0%) showed clear evidence of the PGL-Tb antigen by the dot enzyme-linked immunosorbent assay, but there were marked variations in the intensities and sizes of spots. This suggests differences in PGL-Tb antigen production among M. tuberculosis strains even when they are grown in the same culture media and conditions. This was most evident from the fact that in only eight (16.0%) of the isolates examined was the PGL-Tb antigen detectable by thin-layer chromatography, which is much less sensitive for the detection of glycolipid antigens. This study shows that monoclonal antibodies specific to PGL-Tb are useful in detecting the antigen in lipid extracts and that there is a marked variation in the PGL-Tb production among M. tuberculosis clinical isolates.

Antibodies, Bacterial↗

PubMed1992

Control of cell density and pattern by intercellular signaling in Myxococcus development.

Myxococcus xanthus cells feed, move, and develop cooperatively. Genetic, biochemical, and cell mosaic studies demonstrate that cells coordinate their multicellular behavior by transmission of intercellular signals. Starvation for amino acids at sufficiently high density on a solid surface initiates a series of events culminating in the formation of a multicellular structure called a fruiting body filled with dormant, environmentally resistant spores. This review discusses how myxobacteria use extracellular signals to sequentially check the density and arrangement of cells at different stages during development. For at least one early and one late developmental signal, cell density determines the efficiency of intercellular signaling. In turn, proper signaling insures that the appropriate cell density exists, thus controlling the progress of multicellular development in M. xanthus.

Colony Count, Microbial↗

PubMed1992

Clinical and immunological evaluation of isocyanate-exposed workers.

Isocyanates are the most significant cause of occupational asthma in our country. To evaluate the prevalence of work-related respiratory symptoms and immunologic sensitization to it, we performed a questionnaire survey, allergy skin test, radioallergosorbent test (RAST) to toluene diisocyanate (TDI)-human serum albumin (HSA) conjugate and methacholine bronchial challenge test on 23 isocyanate-exposed employees and 9 unexposed controls working in a zipper factory. Six employees (26.1%) complained of work-related respiratory symptoms and three symptomatic workers showed significant bronchoconstrictions on TDI-bronchoprovocation test. Three (13%) asymptomatic workers had high specific IgE antibodies to TDI-HSA and none of the TDI-sensitive asthmatic workers had specific IgE antibody. One of the TDI-sensitive asthmatic workers showed a negative result on the initial methacholine bronchial challenge test, but bronchial hyperresponsiveness developed after the TDI challenge. It was suggested that TDI-sensitive asthma was noted in three (13%) of 23 exposed workers and that asymptomatic workers could have high specific IgE antibody. Measurement of the changes in bronchial hyperresponsiveness after the TDI challenge could be helpful to diagnose TDI-sensitive asthma.

Adult↗

PubMed1992

Natural killer activity and antibody-dependent cellular cytotoxicity in patients with primary lung cancer.

The NK activity and ADCC of peripheral blood mononuclear cell were examined to evaluate the contribution of ADCC and NK activity to host immune response against lung cancer. The NK activity and ADCC were examined in 58 patients with primary lung cancer and 40 healthy volunteers as normal controls. The NK activity of patients with lung cancer was significantly subnormal, but ADCC was at a normal level. The NK activity was decreased in non-small cell lung cancer (NSCLC), but not in small cell lung cancer (SCLC) compared to normal controls. According to stage, the NK activity in stage II, III-M0 and III-M1 NSCLC showed low levels compared to that of stage I NSCLC, but there was no difference of NK activity in patients with SCLC. The NK activity was not affected by performance status. There was no significant difference of ADCC in patients with lung cancer according to cell type, stage and performance compared with that of normal controls. The NK activity and ADCC were not changed after chemotherapy and operation respectively.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1992

Detection of Mycobacterium tuberculosis in clinical samples from patients with tuberculosis or other pulmonary diseases by polymerase chain reaction.

Polymerase chain reaction (PCR) using primers targeting the IS6110 repetitive sequence was employed to detect Mycobacterium tuberculosis in 228 samples from patients with tuberculosis or other pulmonary diseases and controls, and the results were compared with culture and clinical findings. None of culture negative samples from 17 healthy controls were PCR positive. Of 109 active tuberculosis patients under chemotherapy, 88 (80.7%) were PCR positive and were significantly higher than 63 (57.8%) positive by culture. Fifty-nine (93.7) of 63 culture positive and 29 (63.0%) of 46 culture negative specimens contained M. tuberculosis detectable by PCR. In 41 specimens from inactive tuberculosis patients who visited to the chest clinic because of chest problems, 16 (39.0%) also gave PCR positive results. In addition, 14 (46.7%) of 30 specimens submitted for M. tuberculosis culture from patients with pulmonary diseases were PCR positive. Presumptive diagnosis of these PCR positive patients was bronchitis, pneumonia, bronchial asthma, etc. Therefore, this study suggests that PCR is sensitive and specific in detecting M. tuberculosis in clinical specimens. However, the interpretation of the PCR results in specimens from patients with pulmonary diseases should be done cautiously in areas with a high prevalence of tuberculosis.

Base Sequence↗

PubMed1992

Tuberculosis of the ribs: a recurrent attack of rib caries.

Rib tuberculosis is an extremely rare condition with the incidence not exceeding 3 percent of all skeletal tuberculosis. The authors experienced a recalcitrant case of pulmonary tuberculosis accompanied by chest wall cold abscesses involving ribs recurring at a new site in approximately 10 months despite of medical and surgical treatment. The patient has twice taken thoracotomy for abscess drainage and during the second thoracotomy, a partial resection of involved ribs was performed.

Adolescent↗

PubMed1992

Plasma t-PA and PAl-1 antigen concentrations in non-insulin dependent diabetic patients: effects of treatment modality on fibrinolysis.

Basal plasma tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAl-1) antigen levels were studied in 49 non-insulin dependent diabetic patients (23 men, 26 women: ages 51.3 +/- 14.9 years) and 16 age matched non-diabetic subjects (9 men, 7 women: ages 49.8 +/- 12.2 years) as a control group. Compared to a control group, the diabetic patients had a significantly higher mean t-PA antigen (5.15 +/- 3.02 vs 3.20 +/- 2.30 ng/ml) and PAl-1 antigen (35.89 +/- 18.59 vs 17.60 +/- 15.36 ng/ml) levels (p < 0.05). Plasma t-PA antigen level was not influenced by each treatment modality. There was a significant decrease of plasma PAl-1 antigen level after Metformin administration compared to that of before Metformin administration (39.74 +/- 19.39 vs 25.14 +/- 16.18 ng/ml) (p < 0.05), and the insulin-treated group showed a tendency for a decrease of plasma PAl-1 antigen levels after insulin administration but this did not reach statistical significance (29.93 +/- 15.37 vs 17.32 +/- 10.60 ng/ml). Sulfonylurea did not change both plasma t-PA and PAl-1 antigen levels. In conclusion, diabetic patients have high t-PA and PAl-1 antigen levels. Biguanide reduced plasma PAl-1 antigen levels, which might play some helpful role in the improvement of chronic complications in NIDDM.

Antigens↗

PubMed1991

Fatty-acyl iminopolycarboxylates: lipophilic bifunctional contrast agents for NMR imaging.

New fatty-acyl contrast agents, N3-2'-myristoyloxyethyl-N6-2'-hydroxyethyl-1, 8-dioxotriethylenetetraamine-N,N,N',N'-tetraacetic acid (MHE-DTTA) and N3,N6-bis(2'-myristoyloxyethyl)-1,8-dioxo- triethylenetetraamine-N,N,N',N'-tetraacetic acid (BME-DTTA) were prepared by sequential alkylation, acylation, and catalytic hydrogenation from bis(hydroxyethyl)-ethylenediamine with satisfactory yields (overall 36-46%). The 1:1 gadolinium complexes of the ligands MHE-DTTA and BME-DTTA were incorporated into liposomes and their relaxivities in vitro were determined. The relaxivities of both agents were similar and were greater than those of Gd3+ aquoion, Gd(EDTA), and Gd(DTPA) at both 0.23 T and 0.47 T. The relaxivities of these two agents increased from the lower to the higher magnetic field, indicating a positive field dependence. This is advantageous because of the widespread use of high-field (B0 greater than 0.5 T) NMR imaging instruments. Stability constants (log K) of Gd(MHE-DTTA) and Gd(BME-DTTA) were found to be 15.27 +/- 2.21 and 16.78 +/- 0.36, respectively. LD50 of both compounds was greater than 0.2 mmol/kg. These stabilities and lower limits of LD50 indicate the possible in vivo application of these agents.

Animals↗

PubMed1991

Inhibition of monoamine oxidase by two substrate-analogues, with different preferences for 5-hydroxytryptamine neurons.

Various intraperitoneal doses of 5-fluoro-alpha-methyltryptamine (5-FMT), given to mice, dose-dependently inhibited only MAOA activity, with similar degrees of inhibition in the striatum, hypothalamus and the rest of the forebrain. The activity inhibited in these regions, completely recovered to control levels within 24 hr after the injection. In contrast, p-chloro-beta-methylphenethylamine (p-CMP), selectively inhibited MAOB activity, with complete recovery within 45 min after the injection. Regardless of the differences in time interval and degree of inhibition of MAOA by 5-FMT or MAOB by p-CMP, both kinds of inhibition were competitive, with respect to oxidation of the respective substrate. 5-Fluoro-alpha-methyltryptamine markedly protected only MAOA against inhibition by phenelzine, without protecting MAOB. Also, 5-FMT greatly increased one kind of animal behaviour, the head-twitch and this behaviour was greatly reduced by treatment with fluoxetine, but increased by reserpine. The results indicate that p-CMP is a short-acting, probably reversible, MAOB-selective inhibitor and 5-FMT has the same characteristics of selectivity for MAOA in central serotonergic neurons.

Animals↗

PubMed1991

Effects of age on diabetes- and insulin-induced changes in pancreatic levels of alpha-amylase and its mRNA.

During aging, protein synthesis undergoes decremental changes in many organs and tissues. In the pancreas, as well as in other exocrine glands, the rate of protein synthesis declines with age. However, it is unknown whether this decline is related to intrinsic aging changes which affect the secretory cell function. In this study, we compared the ability of pancreatic acinar cells to synthesize amylase and its messenger RNA (mRNA) in response to insulin treatment of young and old rats rendered diabetic with streptozotocin (STZ). In STZ-induced diabetic rats, amylase protein and its mRNA levels were reduced drastically in the pancreas of young and old groups. Injections of these diabetic rats with insulin increased pancreatic amylase mRNA contents significantly in both young and old rats. Insulin also increased proportions of amylase protein synthesis in the pancreas of both age groups. These results indicate that the pancreatic cells remain effective during aging in their transcriptional activity for functional amylase mRNA in response to an exogenous stimulus of insulin.

Aging↗