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Biomedical subjects

H Kang

Publications and source records attributed to H Kang.

At least 127 records · Page 7Linked to original sources

Detection of O6-methylguanine, O4-methylthymine and O4-ethylthymine in human liver and peripheral blood leukocyte DNA.

O6-Methylguanine, O4-methylthymine and O4-ethylthymine were determined by a recently developed, highly sensitive and specific method (PREPI, pre-fractionation, 32P-post-labeling and immunoprecipitation) in human liver DNA obtained from 15 autopsy specimens and in 15 peripheral blood leukocyte DNA samples obtained from healthy volunteers. All the cases had no obvious history of recent occupational or therapeutic exposure to alkylating agents. In the human liver DNA O6-methylguanine was detected in 13 cases at levels of 1.1-6.7 adducts/10(7) guanine; two cases were below the detection limit of approximately 1.1 x 10(-8). O4-Methylthymine and O4-ethylthymine were detected in all the liver samples at levels of 0.1-14 adducts and 0.5-140 adducts/10(7) thymine respectively. The mean value of the ratio of O6-methylguanine to O4-methylthymine was about 6. Among the three DNA adducts measured there was no significant correlation between any two combinations of adducts. In peripheral leukocytes of healthy volunteers O6-methylguanine was detected at 0.7-4.6 adducts/10(8) guanine, this being approximately 3-6% of that in livers. Neither O4-methylthymine nor O4-ethylthymine was above the detection limits. These results suggest that humans are exposed to exogenous and/or endogenous methylating and ethylating agents in daily life.

Adolescent↗

Protocol for ACTH administration in refractory childhood seizures: educational strategies.

Adrenocorticotropic hormone (ACTH) in gel form is increasingly being used in the treatment of a variety of childhood seizure disorders. The therapy involves intramuscular injections and can be associated with significant morbidity. A teaching/learning plan for parents or caregivers based on Knowles' theory of adult learning was developed and incorporated into the ACTH protocol presented here. Twenty-nine families completed this protocol. Despite a wide range of educational levels and support systems, all caregivers proved capable of administering the medication. Few complications were encountered. In interviews with the caregivers regarding the teaching-learning process, caregivers believed it contributed to their ability to complete the therapeutic program.

Adrenocorticotropic Hormone↗

Interaction of the cell-binding domain of fibronectin with VLA-5 integrin induces monokine production in cultured human monocytes.

The effect of fibronectin on IL-1 alpha, IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), and IL-6 production was investigated with cultured monocytes isolated from human peripheral blood. Monokine concentrations were determined by both ELISA and bioassay. Fibronectin markedly stimulated the secretion of IL-1 alpha, IL-1 beta, TNF-alpha and IL-6 from cultured monocytes in a dose-dependent manner, with the maximal effect apparent within 24 h. Northern blot analysis revealed a marked increase in the abundance of mRNA specific for each monokine on exposure of monocytes to fibronectin. Monoclonal antibodies to the alpha chain of very late antigen (VLA)-5, the beta 1 integrin, the alpha chain of Mac-1, and the beta 2 integrin, as well as the synthetic peptide of GRGDSP (which corresponds to the cell-binding domain of fibronectin), inhibited (> 50%) fibronectin-induced monokine production. Monoclonal antibodies to the alpha chain of VLA-4, and the alpha chain of LFA-1, as well as the synthetic peptide CS-1 (which corresponds to the alternatively spliced connecting segment of fibronectin) and the control peptide GRADSP, had no inhibitory effect on monokine production. A MoAb, R60, that recognizes an epitope of the fibronectin molecule that includes the RGD sequence, inhibited monokine production, whereas the MoAb Y16, which recognizes another epitope of fibronectin not including RGD, did not. These results indicate that fibronectin-induced production of IL-1 alpha, IL-1 beta, TNF-alpha and IL-6 from cultured monocytes is mediated predominantly by interaction of the cell-binding domain of fibronectin with VLA-5, although Mac-1 also may contribute to this effect of fibronectin. Our results indicate that the interaction of fibronectin with integrins may contribute to the cytokine network in inflammatory response.

Binding Sites↗

Gabapentin toxicity in children manifesting as behavioral changes.

Pediatric experience with gabapentin (GBP), a new antiepileptic drug (AED), is limited. We described 3 learning disabled children, 1 aged 7 and 2 aged 10 years, with intractable partial seizures who developed severe behavioral problems while receiving modest doses of GBP. The children became hyperactive and had explosive outburst consisting of aggressive and oppositional behavior. The behavioral problems were sufficiently severe to require discontinuation of GBP despite moderately improved seizure control.

Acetates↗

Interactions of oligonucleotide analogs containing methylphosphonate internucleotide linkages and 2'-O-methylribonucleosides.

The interactions of oligonucleotide analogs, 12-mers, which contain deoxyribo- or 2'-O-methylribose sugars and methylphosphonate internucleotide linkages with complementary 12-mer DNA and RNA targets and the effect of chirality of the methylphosphonate linkage on oligomer-target interactions was studied. Oligomers containing a single Rp or Sp methylphosphonate linkage (type 1) or oligomers containing a single phosphodiester linkage at the 5'-end followed by 10 contiguous methylphosphonate linkages of random chirality (type 2) were prepared. The deoxyribo- and 2'-O-methylribo- type 1 12-mers formed stable duplexes with both the RNA and DNA as determined by UV melting experiments. The melting temperatures, Tms, of the 2'-O-methylribo-12-mer/RNA duplexes (49-53 degrees C) were higher than those of the deoxyribo-12mer/RNA duplexes (31-36 degrees C). The Tms of the duplexes formed by the Rp isomers of these oligomers were approximately 3-5 degrees C higher than those formed by the corresponding Sp isomers. The deoxyribo type 2 12-mer formed a stable duplex, Tm 34 degrees C, with the DNA target and a much less stable duplex with the RNA target, Tm < 5 degrees C. In contrast, the 2'-O-methylribo type 2 12-mer formed a stable duplex with the RNA target, Tm 20 degrees C, and a duplex of lower stability with the DNA target, Tm < 5 degrees C. These results show that the previously observed greater stability of oligo-2'-O-methylribonucleotide/RNA duplexes versus oligodeoxyribonucleotide/RNA duplexes extends to oligomers containing methylphosphonate linkages and that the configuration of the methylphosphonate linkage strongly influences the stability of the duplexes.

Adenosine↗

Infrared linear dichroism reveals that A-, B-, and C-DNAs in films have bases highly inclined from perpendicular to the helix axis.

Infrared linear dichroism has been employed to investigate the inclination of the bases in films of poly[d(AC)].poly[d(GT)], poly[d(AG)].poly[d(CT)], and natural DNAs (from Escherichia coli and calf thymus). All DNAs investigated assume the B-form at high (> 94%) relative humidity. Poly[d(AC)].poly[d(GT)], E. coli DNA, and calf thymus DNA assume the A-form at low (75%) relative humidity, whereas poly[d(AG)].poly[d(CT)] assumes the C-form at low (66%) relative humidity. Infrared linear dichroism demonstrates that the bases for DNA in films are highly inclined from perpendicular to the helix axis, even for B-DNA. C-DNA has almost same inclinations as in B-DNA, and the inclinations are slightly increased in A-DNA. These inclination angles confirm our earlier UV linear dichroism results for the orientation of the bases for DNA in solution. Infrared linear dichroism has also been used to obtain conformational angles for the phosphodiester backbone geometry of the A-, B-, and C-forms of DNA.

Animals↗

Discontinuing antiepileptic drugs in children with epilepsy: a prospective study.

In a prospective study, antiepileptic drugs were discontinued in 264 children with epilepsy after a mean seizure-free interval of 2.9 years. They were then followed for a mean of 58 months to ascertain whether seizures recurred. Seizures recurred in 95 (36%) of the children. Etiology was a significant predictor of outcome (relative risk [RR] = 1.81). On multivariable analysis, significant factors in the idiopathic group included age at onset above 12 years (RR = 5.4), a family history of seizures (RR = 3.1), the presence of slowing on the electroencephalogram prior to medication withdrawal (RR = 2.4), and a history of atypical febrile seizures (RR = 2.8). Specific epileptic syndromes such as juvenile myoclonic epilepsy and benign rolandic epilepsy were also significant predictors of outcome. In the remote symptomatic group, significant predictors of outcome included age at onset older than 12 years (RR = 3.6), moderate to severe mental retardation (IQ < 50) (RR = 2.8), a history of atypical febrile seizures (RR = 2.0), and a history of absence seizures (RR = 0.4). The majority of children with epilepsy in remission while on antiepileptic drug therapy will remain seizure free when medications are withdrawn. A few readily available parameters distinguish those with a good prognosis from those in whom seizures are likely to recur. These data provide the framework for the clinical decision making for withdrawal of medications in these children.

Anticonvulsants↗

Flow linear dichroism and Fourier transform IR spectra reveal geometry for X-form DNA.

Flow linear dichroism measurements extended into the vacuum uv region yield inclinations for the base normal from the helix axis of 21 degrees for dA and 40 degrees for dT in the X-form of poly(dAdT).poly(dAdT). These inclination angles are similar to the B form of the synthetic polymer, but the axes around which the bases incline are different. Hydrogen-bonded base pairs are consistent with the geometry for the standard B, C, D, and Z forms of natural DNA, but will not fit into the A form. Fourier transform ir spectra indicate that the X form has sugar pucker and phosphate geometry similar to B-form DNA, and supports the dinucleotide repeat with two kinds of phosphates seen in earlier work, in analogy to Z-form DNA. Clearly, X-form DNA has a unique geometry.

Biopolymers↗

Towards the development of a bioartificial pancreas: immunoisolation and NMR monitoring of mouse insulinomas.

A promising method for diabetes treatment is the implantation of immunoisolated cells secreting insulin in response to glucose. Cell availability limits the application of this approach at a medically-relevant scale. We explore the use of transformed cells that can be grown to large homogeneous populations in developing artificial pancreatic tissues. We also investigate the use of NMR in evaluating, non-invasively, cellular bioenergetics in the tissue environment. The system employed in this study consisted of mouse insulinoma beta TC3 cells entrapped in calcium alginate/poly-L-lysine (PPL)/alginate beads. The PPL layer imposed a molecular weight cutoff of approximately 60 kDa, allowing nutrients and insulin to diffuse through but excluding high molecular weight antibodies and cytotoxic cells of the host. We fabricated a radiofrequency coil that can be double-tuned to 1H and 31P, and an NMR-compatible perfusion bioreactor and support circuit that can maintain cells viable during prolonged studies. The bioreactor operated differentially, was macroscopically homogeneous and allowed the acquisitions of 1H images and 31P NMR spectra in reasonable time intervals. Results indicated that entrapment had little effect on cell viability; that insulin secretion from beads was responsive to glucose; and that the bioenergetics of perfused, entrapped cells were not grossly different from those of cells never subjected to the immobilization procedure. These findings offer promise for developing an artificial pancreatic tissue for diabetes treatment based on continuous cell lines.

Alginates↗

31P changes as a measure of therapy response in human osteosarcomas implanted into nude mice.

Our objective was to determine whether changes in PME and PCr/Pi can be used to predict lack of tumor response to chemotherapy in a murine model of human osteosarcoma. A chemotherapy-sensitive human osteosarcoma cell line was implanted into the flank of 22 nude mice. Cisplatin was administered to 11 of the mice 9 days postimplantation. 31P MR spectroscopy was performed pre- and post-chemotherapy in both sets of mice. Statistically significant changes in PCr/Pi occur from post-chemotherapy in the treated mice, but not in the untreated mice during the same time. Change in PME parallels changes in tumor volume. Changes in PCr/Pi predict lack of chemotherapy treatment in human osteosarcoma implanted into nude mice with a specificity of 80% and a sensitivity of 63%. The change in PCr/Pi occurs prior to any changes in volume of the tumor [corrected].

Animals↗

Regulation of early flowering in Pinus banksiana.

Seedlings of three families of jack pine (Pinus banksiana Lamb.) were subjected to 16 combinations of photoperiod, growth environment (outdoors, greenhouse and biotron) and gibberellin (GA(4/7)) treatment. After 14 months, which included two dormancy induction periods, ovulate flowering was observed. There was a strong positive correlation between flowering and seedling height; female flower production was stimulated by both a declining photoperiod during bud development and GA(4/7) treatment; and there was an interaction between GA(4/7) treatment and family, such that the difference in flowering intensity between a late-flowering and an early-flowering family was eliminated by GA(4/7) treatment. The results suggest that the genetic control over the time of onset of flowering, and GA(4/7)-induction of flowering depend on a common mechanism.

Journal Article↗

Tick bites in Korea.

BACKGROUND: Tick bites are dermatoses not commonly encountered in Korea. Recognizing their clinical signs as well as their histopathologic findings is important in making a diagnosis of tick-related dermatoses. The incidence and causative species are different depending on the geographic areas. The histopathologic findings of tick bites are known to be a variable depending on the species of ticks involved and the duration of their bloodsucking. METHODS: Five ticks were collected from five patients and three of them were identified as Ixodes (I.) nipponensis. RESULTS: Histopathologic findings of panniculitis were prominent in four of five cases; septal panniculitis in two cases, and lobular panniculitis in the other cases. CONCLUSIONS: Ixodes nipponensis was the most common causative species of ticks responsible for tick bites in Korea, and tick bite panniculitis must be considered in the differential diagnosis of panniculitis which is mainly composed of neutrophils.

Aged↗

Progressively intractable seizures, focal alopecia, and hemimegalencephaly.

We report a 3-year-old boy with the neurocutaneous combination of unilateral alopecia, ipsilateral hemimegalencephaly, and intractable seizures. He was born with an asymmetric hair pattern consisting of absent patches of hair, a small left eyebrow, and less eyelashes on the left eye; he had normal development until age 17 months, when he experienced right focal seizures with fever. Two months later, fever triggered new seizures characterized by flurries of head and body flexion and adduction of the right arm. He had left hand preference and language regression. EEG manifested left hemihypsarrhythmia, and MRI showed left hemimegalencephaly with marked enlargement of the temporal lobe with ventriculomegaly. Seizures were refractory to treatment with phenobarbital, adrenocorticotropic hormone, pyridoxine, sodium valproate, clonazepam, carbamazepine, phenytoin, and felbamate. This may represent a previously undescribed neurocutaneous syndrome.

Alopecia↗

Linear dichroism demonstrates that the bases in poly[d(AC)].poly[d (GT)] and poly[d(AG)].poly[d(CT)] are inclined from perpendicular to the helix axis.

Flow linear dichroism is used to measure specific inclinations for each of the four bases in poly[d(AC)].poly[d(GT)] and poly[d(AG)].poly[d(CT)] in both the B and A forms. For the B form in solution the bases are found to have a sizable inclination. Inclination is increased in the A form, as expected. In all cases the pyrimidines are more inclined than the purines.

Adenine↗

Increased soluble IL-2 receptor in serum of patients with systemic lupus erythematosus.

We estimated the concentration of soluble IL-2R (sIL-2R) in the serum of patients with systemic lupus erythematosus (SLE) and examined the relationship between the serum levels of sIL-2R and clinical features or laboratory data. We found that elevated levels of sIL-2R were present in the serum of SLE patients with discoid rash, and sIL-2R concentrations were correlated with the soluble CD4 and soluble CD8 concentrations but not with classical serological marker, anti-DNA antibody or complement titer.

Adolescent↗