Biomedical subjects

H Kang

Publications and source records attributed to H Kang.

At least 19 recordsLinked to original sources

PubMed1995

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↗

PubMed1994

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↗

PubMed1992

Stacking interactions of ApA analogues with modified backbones.

CD spectra have been measured as a function of temperature for a number of ApA analogues with modified backbones. Oligonucleotides with these modified backbones are being used as antisense agents having potential as viral therapeutics. Results of these studies show that when a carbonyl is substituted for the phosphate to produce an uncharged backbone, the analogues that have either sugar or morpholino substitution do not stack. In contrast, when a morpholino group is substituted for the sugar and the phosphate is modified so as to be uncharged, there is strong base stacking. Stacking interactions in the phosphorus-linked morpholino analogues are at least as strong as those found in d(ApA). The stacking interactions in ApA are weak by comparison. Singular value decomposition demonstrates that the stacking is two state, and Taylor series decomposition yields a coefficient that measures base stacking interactions. The van't Hoff equation is applied to the base stacking coefficient from the Taylor series fitting to give thermodynamic parameters.

Circular Dichroism↗

PubMed1992

High susceptibility of analbuminemic rats to neurogenic tumor induction by transplacental administration of N-ethyl-N-nitrosourea.

The susceptibilities of Nagase analbuminemic rats (NAR) and control Sprague-Dawley rats (SDR) to N-ethyl-N-nitrosourea (ENU) were compared. In Experiment I, the rats were given daily subcutaneous injections of 10 mg/kg of ENU for a week from 4 weeks of age. In Experiment II, mother rats were given a single subcutaneous injection of 60 mg/kg of ENU on day 17 of pregnancy and tumor development in their offspring was examined. In Experiment I, the incidence of neurogenic tumors was slightly, but not significantly, higher in NAR than in control rats. In Experiment II, the incidence of total tumors including neurogenic tumors was significantly higher in NAR (40/43, 93.0%) than in SDR (13/61, 21.3%). NAR showed particularly high susceptibility to induction of neurogenic tumors (34/43, 79.1%) and renal tumors (15/43, 34.9%). In an attempt to elucidate the underlying mechanisms of the increased susceptibility of NAR to ENU, O6-ethylguanine, a major premutagenic ethylated DNA adduct, was quantitated in fetal brain DNA of NAR and SDR after a pulse exposure to 60 mg/kg ENU. No significant difference in the initial formation or subsequent repair of O6-ethylguanine was observed in the two strains, indicating that abnormality at some later stage(s) of chemical carcinogenesis may lead to the increased susceptibility of NAR to induction of neurogenic tumors.

Animals↗

PubMed1991

Plasmids for recombination-based screening.

To facilitate recombination-based screening, we constructed the ColE1-based plasmid, pi G4, that confers chloramphenicol resistance, contains a polylinker with multiple unique restriction enzyme recognition sequences, and contains the genetic marker, supF. To facilitate recombination-based screening followed by rapid DNA sequencing, we inserted the selectable marker, supF, into each of 20 high-copy-number (hcn) pUC-derived NoC plasmids that were designed for multiplex DNA sequencing. To facilitate recombination-based screening of common cDNA libraries that often contain ColE1 sequences, we constructed a supF-carrying plasmid whose replication was driven from an R6K replicon that does not share sequence homology with ColE1. Furthermore, we incorporated a useful polylinker and increased the copy number of this plasmid to create the 4.4-kb hcn plasmid, pMAD1. Thus, these plasmids allow: (1) background-free transformation of cells by a supF plasmid carrying an antibiotic-resistance marker; (2) simultaneous performance of the recombination-based assay and DNA sequencing; and (3) screening bacteriophage cDNA libraries that contain ColE1 sequences by recombination with a supF plasmid that is not homologous to ColE1 derivatives.

Bacteriophage lambda↗

PubMed1991

Specific HLA-DQA and HLA-DRB1 alleles confer susceptibility to Sjögren's syndrome and autoantibody production.

Primary Sjögren's syndrome (1. SS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary glands and autoantibody production. In order to identify genetic factors that play a role in pathogenesis and predict extent of disease, we used Southern blot and polymerase chain reaction (PCR) methods to detect polymorphisms of the HLA-DRB1 (DR), HLA-DRB3 (DRw52), and HLA-DQA1 genes among 75 Caucasoid 1. SS patients and 150 Caucasoid controls living in the same geographic region of Southern California. We found significantly increased frequency of HLA-DR3 (P less than .001), HLA-DW52a (P less than .001), and HLA-DQA4 (P less than .05), in comparison to normal controls. Also, an increased frequency of heterozygosity for HLA-DQA1/DQA4 (P less than .05) was present among 1. SS patients. Autoantibodies to SS-A and to SS-B were significantly associated with DR3 (P less than .001), HLA-DQA4, (P less than .05), and DQA4/DQA1 heterozygotes (P less than .01). Among the 1. SS patients, clinical and laboratory features such as hypergammaglobulinemia, symmetric peripheral neuropathy, and hypothyroidism were significantly associated with HLA-DR3 (P less than .01) but not with HLA-DR2 (P greater than .10). In comparison, 1. SS patients with leukocytoclastic vasculitis were more frequently HLA-DR2 (P less than .05). These results using PCR methods confirm and extend prior studies that have used serologic methods.

Adolescent↗

PubMed1991

Impaired tumour necrosis factor-alpha (TNF-alpha) production and abnormal B cell response to TNF-alpha in patients with systemic lupus erythematosus (SLE).

We examined the TNF-alpha activity in culture supernatants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients with SLE stimulated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan 1 secreted significantly lower amounts of TNF-alpha than did normal monocytes. A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by mitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNF-alpha (rTNF-alpha) on the B cell function in SLE patients. rTNF-alpha inhibited the spontaneous B cell proliferation of SLE, but tended to enhance the normal B cell proliferation. Spontaneous IgM production from SLE B cells was inhibited by rTNF-alpha, but that from normal B cells was not. Spontaneous IgG production was unaffected by rTNF-alpha. Also, rTNF-alpha did not affect the viability of B cells. These findings suggest that an impaired TNF-alpha production and an abnormal B cell response to TNF-alpha play a role in the immunological dysfunction in patients with SLE.

B-Lymphocytes↗

PubMed1991

Correlations between IL-2 enhancing activity and clinical parameters in patients with rheumatoid arthritis and systemic lupus erythematosus.

In a previous paper (Tomura, K. et al. Tohoku J. Exp. Med., 1989, 159, 171-183), we discovered IL-2 enhancing factor(s) designated B cell derived-growth enhancing factor-2 (BGEF-2), which enhanced IL-2 dependent cell proliferation, and reported that BGEF-2 was produced by B cells of the patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) only when they were in the active stage of the disease. In this paper, we studied relationship between each IL-2 enhancing activity from B cell supernatant of the patients with these diseases and clinical parameters. IL-2 enhancing activities did not correlate with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), but correlated with plasma concentrations of gamma-globulin from the patients with RA and SLE in the active stages. IL-2 enhancing activities correlated with hypocomplementemia and leukocytopenia in the patients with SLE, and also correlated with RAHA titer in the patients with RA. Moreover, on several patients with RA or SLE in the active stages, diminution of IL-2 enhancing activity was found when they were in the remission stage after treatments. These findings suggested that IL-2 enhancing activity (i.e., BGEF-2 activity) correlated with activity of these diseases and supported the hypothesis that BGEF-2 played an important role in the polyclonal B cell activation and autoantibody production in patients with these diseases.

Adult↗

PubMed1990

Insulin regulates the paracellular permeability of cultured intestinal epithelial cell monolayers.

The T84 human colonic epithelial cell line retains the ability to produce secretagogue-responsive monolayer cultures with high transepithelial resistance when grown and maintained on collagen-coated permeable supports in media supplemented with 5% newborn calf serum. The addition of highly purified insulin to the basolateral but not the apical membrane side of established monolayers caused the transepithelial resistance to decline more than eightfold over a 3-4-d period. By comparing the transepithelial flux of 22Na with that of the extracellular space marker, [3H]mannitol, the decline in electrical resistance was shown to be due solely to an effect on tight junction-mediated paracellular permeability. The effect of insulin was dose dependent with a half-maximal effect at 3.9 ng/ml (approximately 0.7 nM) and fully reversible over a 10-d time course. Simultaneous addition of 2 microM cycloheximide prevented the insulin-induced decline in resistance; in fact, this combination caused a significant increase in electrical resistance. There was no effect on the short-circuit current response of insulin-treated monolayers to secretagogues so long as media was changed daily. While no gross morphological changes were apparent, there did appear to be a subtle condensation of the perijunctional actin ring as visualized using rhodamine-labeled phalloidin. These results demonstrate that insulin modulates the permeability of the occluding junction in T84 cell monolayers through a receptor mediated process which probably involves changes in protein synthesis and cytoskeletal structure. Insulin was also shown to produce similar effects on two other intestinal epithelial cell lines.

Animals↗

PubMed1990

A case of methimazole-induced acute hepatic failure in a patient with chronic hepatitis B carrier.

We report a case of methimazole-induced acute hepatic failure, which occurred 17 weeks after initiation of the drug in a 43-year-old man with hyperthyroidism and hepatitis B surface antigenemia. Postmortem needle autopsy of the liver revealed an established micronodular cirrhosis secondary to hepatitis B with moderate septal/portal inflammation, marked cholestasis and scattered acidophilic bodies. The serum hepatitis B surface antigen (HBsAg) was positive, but reactivation of hepatitis B was unlikely in view of the absence of a serum hepatitis B e antigen (HBeAg) and hepatitis B virus deoxyribonucleic acid (HBV-DNA) and negative stain for HBsAg and hepatitis B core antigen (HBcAg) in the liver tissue.

Acute Disease↗

PubMed1990

Risk of seizure recurrence following a first unprovoked seizure in childhood: a prospective study.

In a prospective study, 283 children who presented with a first unprovoked seizure were followed for a mean of 30 months from the time of first seizure. Subsequent seizures were experienced by 101 children (36%). The cumulative risk of seizure recurrence for the entire study group was 26% at 12 months, 36% at 24 months, 40% at 36 months, and 42% at 48 months. The cumulative risk of recurrence in the 47 children with a remote symptomatic first seizure was 37%, 53%, and 60% at 12, 24, and 36 months, respectively, compared with a cumulative risk of 24%, 33%, and 36% at 12, 24, and 36 months, respectively, in the 236 children who had had an idiopathic first seizure (P less than .01). In children with an idiopathic first seizure, the electroencephalogram was the most important predictor of recurrence. The cumulative risk of recurrence in the 81 children with abnormal electroencephalograms was 41%, 54%, and 56% at 12, 24 and 36 months, respectively, but only 15%, 23%, and 26% at 12, 24, and 36 months, respectively, in the 138 children with normal electroencephalograms (P less than .001). A history of epilepsy in a first-degree relative was a significant risk factor only in idiopathic cases with abnormal electroencephalograms. In children with a remote symptomatic first seizure, either a history of prior febrile seizures or the occurrence of a partial seizure were significant predictors of recurrence. Age at first seizure and duration of seizure did not affect recurrence risk in either the idiopathic or remote symptomatic group. A total of 84% of the children were not treated with antiepileptic drugs or were treated for less than 2 weeks. Only 9% were treated for longer than 3 months. Treatment did not affect the risk of recurrence. The results suggest that, even without treatment, the majority of children with a first unprovoked seizure will not experiment a recurrence. Children with an idiopathic first seizure and a normal electroencephalogram have a particularly favorable prognosis.

Adolescent↗

PubMed1989

Expression of Leu M1 antigen on a monoclonal B cell line established from a patient with rheumatoid arthritis.

The purpose of this study is to show that anti-Leu M1 antibody (anti-CD15), which has different staining characteristics in lymphoid and non-lymphoid cells, reacted against the surface antigen of a defined monoclonal B cell line. This antibody recognizes the sugar moiety, lacto-N-fucopentaose (LNF-III), which is linked to the cell membrane protein in several kinds of cells, but not in B cells. However, a human monoclonal B-cell line (TKS-1) which was established from the peripheral blood of a patient with rheumatoid arthritis, expressed the Leu M1 antigen spontaneously. The analysis of surface markers using a fluorescence-activated cell sorter (FACS) has revealed that the surface markers of TKS-1 were anti-mu, delta, kappa, HLA-DR, DQ, Leu 12 (CD19) and Leu M1 (CD15). TKS-1 cells were not reactive with any of the following antibodies: anti-OK M1 (CD11b), Leu M2, Leu M3 (CD14), Leu M4, Leu 1 (CD5), Leu 2 (CD8), Leu 3 (CD4), Leu 4 (CD3), Leu 7 and Leu 11 (CD16). In addition, TKS-1 was positive to Epstein-Barr nuclear antigen, weakly positive to non-specific esterase without staining inhibition by NaF, and negative to peroxidase. TKS-1 cells produced IgM in the culture supernatant and have kappa-light chain rearrangement in its DNA. As shown in other studies, distribution of Leu M1 is very wide. This antigen is not a specific immunodiagnostic marker to distinguish the cell type. We conclude that it is possible to express Leu M1 antigen on the membrane of a B-cell lineage cell.

Antibodies, Monoclonal↗

PubMed1989

IL-2 enhancing factor(s) in B cell supernatants from patients with rheumatoid arthritis or systemic lupus erythematosus.

Culture supernatants of B cells from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in the active stage enhanced interleukin 2 (IL-2) dependent proliferation of CTLL A/J cells. This activity, designated B cell-derived growth-enhancing factor-2 (BGEF-2), was recovered by gel filtration of a molecular weight between 15,000 and 20,000. BGEF-2 itself did not show IL-2 activity nor IL-1 activity, and BGEF-2 activity was not detected in the following cytokines: Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 6 (IL-6). Furthermore, BGEF-2 was distinguishable from B cell-derived growth-enhancing factor described in a previous paper [Kang et al. (1987) J. Immunol., 139, 1154-1160]. BGEF-2 was produced by B cells from patients with RA or SLE only when the patients were in the active stage. BGEF-2 enhanced IL-2-dependent growth of peripheral blood T cells from patients with active RA, but did not enhance the growth of T cells from healthy volunteers. These results suggest that BGEF-2 is a B cell-derived lymphokine which plays an important role in the pathogenesis of RA and SLE.

Adolescent↗

PubMed1989

CD4/Leu7 and CD8/Leu7 large granular lymphocytosis: comparative studies between NK cells and T cells.

Lymphocytes, co-expressing CD4/Leu7 and CD8/Leu7 markers respectively, taken from two patients having large granular lymphocytosis taking an indolent clinical course have been comparatively studied for function as NK cells and T cells. Both large granular lymphocytes (LGLs) were acid phosphatase positive and showed a beta-glucuronidase reaction in their cytoplasmic granules. Studies on case 1 indicated that the CD4/Leu7 lymphocytosis with LGL morphology takes a benign clinical course with mild neutropenia as well as those of CD8/Leu7 LG lymphocytosis. Both CD4/Leu7 and CD8/Leu7 LGLs behave similarly in their lack of NK activity, and manifest decreased IL-2 production in vitro and show a low IL-2 receptor expression unrelated to their T cell phenotype, but behave differently in influencing the immunoglobulin production in vitro and the ADCC activity, depending on their T cell phenotype and on the expression of Fc receptor, respectively. Furthermore, the altered Fc receptors which were undetectable by the Leul 1 antibody but were still effective for ADCC activity might be present in case 2 LGLs.

Aged↗

PubMed1987

Characterization of a B cell-derived growth-enhancing factor produced by a human B cell line established from a patient with rheumatoid arthritis.

A human B cell line, TKS-1, which was established from the peripheral blood of a patient with rheumatoid arthritis, was found to spontaneously produce a factor which enhances the activity of interleukin 1 (IL-1). This factor, designated B cell-derived growth-enhancing factor (BGEF), enhanced IL-1-induced proliferation of peanut agglutinin nonagglutinated thymocytes. BGEF also enhanced IL-1-induced production of interleukin 2 (IL-2) by both thymocytes and a human T cell clone, HSB.2 C5B2. BGEF alone did not induce the production of IL-2. BGEF failed to induce proliferation of the IL-2-dependent T cell clone, and did not enhance its response to IL-2. The activity of BGEF was not blocked by antisera against human IL-1-alpha or human IL-1-beta. Gel filtration analysis revealed that BGEF has a m.w. of 60,000 to 65,000 in its native state. We concluded that BGEF differed from IL-1 and IL-2, but is a novel factor produced by TKS-1 cells. In addition, we found that partially purified B cells from patients with rheumatoid arthritis produced factors which enhanced the activity of IL-1.

Animals↗

PubMed1987

Cerebral blindness and encephalopathy with cyclosporin A toxicity.

We observed acute cerebral blindness and encephalopathy complicating cyclosporin A (CyA) toxicity in a 5-year-old transplantation patient. Serum CyA level was 1,704 ng/ml (normal, less than 300 ng/ml). Additional neurologic complications of CyA toxicity will be reviewed.

Brain Diseases↗

PubMed1987

Soft tissue sarcoma and military service in Vietnam: a case-control study.

A case-control study was conducted in men who were of draftable age during the Vietnam conflict to examine the association of soft tissue sarcomas (STSs) with military service in Vietnam as well as other host and environmental risk factors. A total of 217 STS cases selected from the Armed Forces Institute of Pathology were compared to 599 controls for Vietnam service, occupational and nonoccupational exposure to various chemicals, occupational history, medical history, and life-style (smoking, alcohol, coffee, etc.). Military service information was verified by a review of the patient's military personnel records. Other information was ascertained from a telephone interview with either subjects or their next of kin. Cases and controls were stratified on the basis of the hospital type (civilian, Veterans Administration, and military); the Mantel-Haenszel estimate of the odds ratio (OR), adjusted for the effects of the stratification variable, was calculated. Vietnam veterans in general did not have an increased risk of STS when compared to those men who had never been in Vietnam (OR, 0.85; 95% confidence interval, 0.54-1.36). Subgroups of Vietnam veterans who had higher estimated opportunities for Agent Orange exposure seemed to be at greater risk of STSs when their counterparts in Vietnam were taken as a reference group. However, this risk was not statistically significant.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMed1987

Aberration of monokine production and monocyte subset in patients with systemic lupus erythematosus.

We measured the production of interleukin 1 (IL-1) and prostaglandin by adherent cells from patients with systemic lupus erythematosus (SLE). Compared to normal subjects, IL-1 production in the patients was lower but prostaglandin E1 production was higher. Furthermore, examination of monocyte subsets in patients with SLE using monoclonal anti-monocyte/granulocyte antibodies disclosed abnormal expression of membrane antigens on monocytes. It is speculated that aberration of monocyte function is related to impaired monokine production and that membrane antigens play a role in immunodysregulation in patients with SLE.

Humans↗