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Biomedical subjects

J Kim

Publications and source records attributed to J Kim.

At least 577 records · Page 32Linked to original sources

Zim1, a maternally expressed mouse Kruppel-type zinc-finger gene located in proximal chromosome 7.

In analysis of a conserved region of proximal mouse chromosome 7 and human chromosome 19q, we have isolated a novel mouse gene, Zim1 (imprinted zinc-finger gene 1), encoding a typical Kruppel-type (C2H2) zinc-finger protein, located within 30 kb of a known imprinted gene, Peg3 (paternally expressed gene 3). Our studies demonstrate that Zim1 is also imprinted; the gene is expressed mainly from the maternal allele and at high levels only during embryonic and neonatal stages. In contrast to most tissues, Zim1 is expressed biallelically in neonatal and adult brain with slightly more input from the maternal allele. Zim1 produces multiple transcripts that range in size from 7.5 to 15 kb. The 7.5 kb transcript is expressed at highest levels and appears to be embryo specific. Whole mount in situ hybridization analysis indicates that Zim1 is expressed at significant levels in the apical ectodermal ridge of the limb buds during embryogenesis, suggesting a potential role of Zim1 in limb formation. We have identified the potential human ortholog of Zim1 near PEG3 in a conserved, gene-rich region of human chromosome 19q13.4. The close juxtaposition of reciprocally imprinted genes has also been seen in other imprinted regions, such as human 11p15.5/Mmu7 ( H19 / Igf2 ) and suggests that the two genes may be co-regulated. These and other data suggest the presence of an unexplored, conserved imprinted domain in human chromosome 19q13.4 and proximal Mmu7.

Amino Acid Sequence↗

Protective immune correlates can segregate by vaccine type in a murine herpes model system.

A central tenet of vaccine development is to identify immune correlates of protection. Both plasmid-encoded gD as well as recombinant protein gD can protect mice from lethal herpes simplex virus (HSV) challenge. It is known that different vaccine modalities should induce different immune phenotypes. Yet, paradoxically, it is also thought that the basis for protection should rely on exploitation of vulnerabilities of the pathogen and therefore that the overlapping properties of these different vaccines would reveal insight into common immune mechanisms responsible for protection. We sought to investigate this question by comparing two different vaccine modalities in the HSV-2 mouse model. We observed that gD protein was a strong inducer of T(h)2-type immune responses, and overall antibody titers of IgG, IgE and IgA were significantly higher than those induced by plasmid gD vaccines. In contrast, the plasmid gD vaccine induced a strong T(h)1 bias. Following high-dose challenge the gD protein was most effective at providing protection. However, at lower lethal dose challenge, while both vaccines were protective with regards to survival, only the plasmid-vaccinated animals were protected from HSV-2 infection-induced morbidity. These studies suggest that these different vaccine modalities induce protection through unique non-overlapping mechanisms, supporting that vaccine correlates are associated with the types of immunogen rather than solely the pathogen.

Animals↗

The effects of rapacuronium on histamine release and hemodynamics in adult patients undergoing general anesthesia.

UNLABELLED: Neuromuscular blocking drugs may have variable effects on heart rate (HR) and blood pressure. Rapacuronium is a rapid-acting, steroidal-derived neuromuscular blocking drug whose hemodynamic effects have not been characterized. We studied the effects of 1, 2, and 3 mg/kg rapacuronium on histamine release, HR, and blood pressure in 47 ASA physical status II or III adult patients after the induction of anesthesia with etomidate/fentanyl/N2O. Plasma histamine concentrations were measured before induction and immediately before and 1, 3, and 5 min after the rapid administration of rapacuronium. Mean arterial pressure (MAP) decreased after rapacuronium administration, but there were no significant differences among the groups for changes in HR or MAP, and there was no correlation between changes in MAP or HR and increases in histamine levels. There were no changes in HR or MAP among five patients who had significant (> or = 1 ng/mL) increases in histamine from baselin. Seven patients had bronchospasm without increases in plasma histamine levels. Rapacuronium 2-3 mg/kg increased plasma histamine levels. However, clinically significant histamine-related sequelae did not occur in this population with 1- to 3-mg/kg doses of rapacuronium, and cardiovascular changes were not directly correlated with histamine release. Rapacuronium administration can produce hypotension via mechanisms that do not seem to be related to histamine release. IMPLICATIONS: Rapacuronium, a new steroidal-derived muscle relaxant, may release histamine and produce slight changes in blood pressure and heart rate after administration.

Adult↗

Phase I trial of intoplicine (RP 60475) administered as a 72 h infusion every 3 weeks in patients with solid tumors.

Intoplicine (RP 60475) was selected for a phase I evaluation because it inhibits topoisomerase I and II, and has exhibited antitumor activity against a variety of preclinical solid tumor models. Intoplicine is a 7H-benzo[e]pyrido[4,3-b]indole that inhibits DNA nicking and closing reactions by stabilizing the cleavable complex, a transient intermediate in the religation reaction involving topoisomerase I and II and DNA. Twenty-eight patients with refractory advanced malignancies who met standard phase I eligibility criteria were enrolled in a dose-escalation study of intoplicine, ranging from 7 to 420 mg/m2/day administered as a continuous 72 h i.v. infusion. Fifty-three courses were administered and evaluated. Myelosuppression (four patients, grade 3; two patients, grade 4) and hepatic toxicity (one patient, grade 3) were dose limiting at 336 mg/m2/day. No objective antitumor responses were observed. The pharmacokinetic parameters of intoplicine were investigated in 11 patients at dose levels of 112 (n=1), 224 (n=3), 336 (n=6) and 420 (n=1) mg/m2/day. Both the area under the plasma concentration versus time curves and the maximum plasma concentrations increased linearly within the dose range studied. Intoplicine content measured in whole blood exceeded that found in plasma by 3- to 7-fold, indicating that red blood cells may serve as a drug reservoir. Preclinical cytotoxic concentrations were not achieved at the dose levels studied.

Adult↗

Cervical cancer screening knowledge and practices among Korean-American women.

Cervical cancer is one of the most common cancers of American women. The Papanicolaou (Pap) smear test for cervical screening is a widely used and effective means to reduce the morbidity and mortality rate from cervical cancer through early detection. Despite these benefits, many women have never been screened or are not screened at regular intervals. The purpose of this study was to examine cervical cancer screening knowledge and practices of Korean-American women. The sample consisted of 159 Korean-American women, 40 to 69 years of age. The 1987 Cancer Control Supplement questionnaire was translated into Korean and used to collect data. Twenty-six percent of the respondents never heard of the Pap smear test. Only 34% of respondents reported having had a Pap smear test for screening. The most frequently cited reason for not having had a Pap smear test was absence of disease symptoms. Results indicate that education and usual sources of health care were significant factors related to having heard of or having had a Pap smear test. The findings from this study have important implications for health practitioners and policy makers who serve this ethnic population.

Adult↗

Evaluation of the effect of lissamine green and rose bengal on human corneal epithelial cells.

PURPOSE: To examine the effects of lissamine green and rose bengal on proliferating human corneal epithelial (HCE) cells in vitro. METHODS: HCE cells derived from explants of discarded corneoscleral rims were cultured by the standard technique. Experimental cells were exposed to 1, 0.5, or 0.1% of either lissamine green or rose bengal for 10 min while control cells were exposed to a phosphate buffer solution (PBS). RESULT: Cell viability was 92% greater for 1% lissamine green (p = 0.013) and 81.2% greater for 0.5% lissamine green (p = 0.006) compared to 1 and 0.5% rose bengal, respectively. The difference between the effect of 0.1% rose bengal and 0.1% lissamine green on cell viability was not statistically significant (p = 0.83). Rose bengal staining of HCE cells was immediate and readily detectable with unaided eyes at all three concentrations, whereas no observable staining of healthy HCE cells was noted with lissamine green. CONCLUSION: Rose bengal adversely affects HCE cell viability and stains normal proliferating HCE cells in contrast to lissamine green, which exhibited neither of these characteristics. Therefore, we recommend the use of lissamine green over rose bengal in evaluating ocular surface disorders.

Adolescent↗

Intracranial mucocele as a complication of endoscopic repair of cerebrospinal fluid rhinorrhea: case report.

OBJECTIVE AND IMPORTANCE: Endoscopic repair of an anterior cranial fossa cerebrospinal fluid (CSF) fistula has gained widespread acceptance. We report a case of mucocele development at the site of an endoscopic CSF leak repair. CLINICAL PRESENTATION: A 46-year-old woman underwent functional endoscopic sinus surgery for nasal obstructive symptoms. The surgery was complicated by an intraoperative CSF leak from the posterior cribriform plate/anterior sphenoid, which was repaired immediately using bone and mucosa grafts. Two years postoperatively, a 13-mm anterior cranial base mass was found incidentally. This mass increased to 20 mm over the next year. INTERVENTION: The anterior cranial base mass was excised via a right frontal craniotomy and confirmed histologically to be a mucocele. CONCLUSION: Endoscopic repair of an anterior cranial base CSF fistula with mucosal grafts may lead to formation of a mucocele.

Bone Transplantation↗

Cloning and molecular analyses of a gibberellin 20-oxidase gene expressed specifically in developing seeds of watermelon.

To understand the biosynthesis and functional role of gibberellins (GAs) in developing seeds, we isolated Cv20ox, a cDNA clone from watermelon (Citrullus lanatus) that shows significant amino acid homology with GA 20-oxidases. The complementary DNA clone was expressed in Escherichia coli as a fusion protein, which oxidized GA(12) at C-20 to the C(19) compound GA(9), a precursor of bioactive GAs. RNA-blot analysis showed that the Cv20ox gene was expressed specifically in developing seeds. The gene was strongly expressed in the integument tissues, and it was also expressed weakly in inner seed tissues. In parthenocarpic fruits induced by 1-(2-chloro-4-pyridyl)-3-phenylurea treatment, the expression pattern of Cv20ox did not change, indicating that the GA 20-oxidase gene is expressed primarily in the maternal cells of developing seeds. The promoter of Cv20ox was isolated and fused to the beta-glucuronidase (GUS) gene. In a transient expression system, beta-glucuronidase staining was detectable only in the integument tissues of developing watermelon seeds.

5' Untranslated Regions↗

Age-related changes in the thyroid hormone effects on malondialdehyde-modified proteins in the rat heart.

To determine the age-related changes in thyroid hormone (TH) effects on malondialdehyde (MDA)-modified proteins in cardiac tissue, rats at 4, 12, and 25 months of age were studied. Hyperthyroidism was induced with daily injection of L-triiodothyronine (15 microg/100 g) intraperitoneally for 10 days. Hypothyroidism was induced with 0. 025% methimazole in the drinking water for 4 weeks. MDA proteins were measured with immunoblots using a specific anti-MDA antiserum. MDA was measured as thiobarbituric acid reactive substance. Hypothyroidism in 4-month-old rats was associated with significant reduction in MDA proteins compared to euthyroid rats (13.4 +/- 5.9% vs. 99.8 +/- 10.4% of controls P < 0.001). Hyperthyroidism did not result in a significant change of MDA proteins. In aged rats, neither hypothyroidism nor hyperthyroidism was associated with significant changes in cardiac MDA proteins. The changes in MDA proteins did not correlate with cardiac MDA concentrations. In young rats, the MDA concentrations (nmol/mg) were significantly reduced in hypothyroidism (2.71 +/- 0.21) and were increased in hyperthyroidism (8.19 +/- 0.78) compared to euthyroid values (5.06 +/- 0.71) P < 0. 01. In aged rats, cardiac MDA content was significantly increased during both hyperthyroidism and hypothyroidism. We conclude that alterations in MDA protein content is yet another potential biochemical effect of TH in cardiac tissue. This particular effect is significantly blunted with age.

Aging↗

Differential neuronal and glial relations with parameters of ictal discharge in mesial temporal lobe epilepsy.

PURPOSE: EEG recordings of spontaneous seizures should provide clues to epilepsy pathogenesis and pathology. We examined onset, propagation, and termination characteristics of spontaneous seizures recorded by intracranial EEG in temporal lobe (TL) epilepsy in relation to neuronal, glial, and synaptic changes in the same tissue. METHODS: All of our patients with intracranial EEG recordings of spontaneous TL seizure onset, subsequent TL resection, and quantitative pathologic analysis of resected tissue were included. Seizure parameters were mean time to initial propagation, mean total electrical duration, uniformity of seizure-onset distribution and location, and percentage of seizures with spiking onset per patient. Tissue was analyzed for glial and neuronal density in hippocampal fields and presence of sprouting. Outcome was classified as seizure free or not. RESULTS: All seizures with onset in resected TL in 62 patients were analyzed. The percentage of each patient's seizures with spike onsets was significantly correlated with glial density in CA3 (p < 0.01). Initial propagation time was significantly and inversely correlated with neuronal density in CA4 (p < 0.02). Electrical seizure duration was significantly correlated with glial density in CA2 and CA3 (p < 0.02). Neuronal and glial density were significantly (and inversely) related to one another only in CAI (p < 0.001). Outcome was most significantly related to uniform hippocampal seizure onset. Presence or absence of sprouting was not significantly related to outcome or any EEG measure. CONCLUSIONS: These results suggest both glia and neurons exert independent influences on the expression of ictal discharges in seizures of medial TL onset. Glial density influenced interictal-ictal transition, whereas neuronal density influenced seizure propagation. These findings may have implications for pathogenesis.

Cell Count↗

Repertoire of human antibodies against the polysaccharide capsule of Streptococcus pneumoniae serotype 6B.

We examined the repertoire of antibodies to Streptococcus pneumoniae 6B capsular polysaccharide induced with the conventional polysaccharide vaccine in adults at the molecular level two ways. In the first, we purified from the sera of seven vaccinees antipneumococcal antibodies and determined their amino acid sequences. Their VH regions are mainly the products of VH3 family genes (candidate genes, 3-23, 3-07, 3-66, and 3-74), but the product of a VH1 family gene (candidate gene, 1-03) is occasionally used. All seven individuals have small amounts of polyclonal kappa+ antibodies (Vkappa1 to Vkappa4 families), although kappa+ antibodies are occasionally dominated by antibodies formed with the product of the A27 Vkappa gene. In contrast, lambda+ anti-6B antibodies are dominated by the antibodies derived from one of 3 very similar Vlambda2 family genes (candidate genes, 2c, 2e, and 2a2) and Clambda1 gene product. The Vlambda2(+) antibodies express the 8.12 idiotype, which is expressed on anti-double-stranded-DNA antibodies. In one case, Vlambda is derived from a rarely expressed Vlambda gene, 10a. In the second approach, we studied a human hybridoma (Dob1) producing anti-6B antibody. Its VH region sequence is closely related to those of the 3-15 VH gene (88% nucleotide homology) and JH4 (92% homology). Its VL region is homologous to the 2a2 Vlambda2 gene (91%) and Jlambda1/Clambda1. Taken together, the V region of human anti-6B antibodies is commonly formed by a VH3 and a Vlambda2 family gene product.

Adult↗

Survey of extended-spectrum beta-lactamases in clinical isolates of Escherichia coli and Klebsiella pneumoniae: prevalence of TEM-52 in Korea.

Two hundred ninety isolates of Escherichia coli were investigated for the production of extended-spectrum beta-lactamases (ESBLs). Fourteen (4.8%) of the 290 strains were found to produce ESBLs. Each of the 14 strains produced one or two ESBLs, as follows: 10 strains produced TEM-52, 1 strain produced SHV-2a, 1 strain produced SHV-12, 1 strain produced a CMY-1-like enzyme, and 1 strain expressed SHV-2a and a CMY-1-like enzyme. Another two strains for which the MICs of ceftazidime and cefoxitin were high, were probable AmpC enzyme hyperproducers. Because of the high prevalence of TEM-52 in E. coli isolates, we further investigated the TEM-type ESBLs produced by Klebsiella pneumoniae in order to observe the distribution of TEM-52 enzymes among Enterobacteriaceae in Korea. All TEM enzymes produced by 12 strains of K. pneumoniae were identified as TEM-52. To evaluate the genetic relatedness among the organisms, ribotyping of TEM-52-producing E. coli and K. pneumoniae was performed. The ribotyping profiles of the organisms showed similar but clearly different patterns. In conclusion, TEM-52 is the most prevalent TEM-type ESBL in Korea.

Bacterial Proteins↗

Two cases of Chromobacterium violaceum infection after injury in a subtropical region.

Chromobacterium violaceum is a gram-negative rod and is isolated from soil and water in tropical and subtropical regions. The species have pigmented and nonpigmented colony types. Infections caused by nonpigmented strains are rare. We report on two cases of infection caused by both pigmented and nonpigmented strains of C. violaceum. Two 24-year-old Korea Airline stewardesses were admitted to Inha University Hospital, Inchon, South Korea, on 9 August 1997, 3 days after an airplane accident in Guam. Both had multiple lacerations on exposed parts of their bodies. There was swelling, tenderness, and pus discharge. The wounds contained many small fragments of stones and weeds. A pigmented strain was isolated from the left hand and a nonpigmented strain was isolated from the left knee of one patient. For the other patient only a nonpigmented strain was isolated from a foot wound. The nonpigmented colonies from the left-knee and the left-foot wounds did not produce any pigment even after an extended period of incubation. The biochemical characteristics were the same for each strain except for oxidase and indole reactions. The pigmented strain was oxidase negative and indole positive, whereas the nonpigmented strains were oxidase positive and indole negative. The patients were successfully treated by debridement and with appropriate antibiotics.

Accidents, Occupational↗

Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 infection.

We recently reported that a cationic peptide, T22 ([Tyr(5,12), Lys(7)]-polyphemusin II), specifically inhibits human immunodeficiency virus type 1 (HIV-1) infection mediated by CXCR4 (T. Murakami et al., J. Exp. Med. 186:1389-1393, 1997). Here we demonstrate that T22 effectively inhibits replication of T-tropic HIV-1, including primary isolates, but not of non-T-tropic strains. By using a panel of chimeric viruses between T- and M-tropic HIV-1 strains, viral determinants for T22 susceptibility were mapped to the V3 loop region of gp120. T22 bound to CXCR4 and interfered with stromal-cell-derived factor-1alpha-CXCR4 interactions in a competitive manner. Blocking of anti-CXCR4 monoclonal antibodies by T22 suggested that the peptide interacts with the N terminus and two of the extracellular loops of CXCR4. Furthermore, the inhibition of cell-cell fusion in cells expressing CXCR4/CXCR2 chimeric receptors suggested that determinants for sensitivity of CXCR4 to T22 include the three extracellular loops of the coreceptor.

Amino Acid Sequence↗

Receptor inhibition of pheromone signaling is mediated by the Ste4p Gbeta subunit.

The pheromone response pathway of the yeast Saccharomyces cerevisiae is initiated in MATa cells by binding of alpha-factor to the alpha-factor receptor. MATa cells in which the a-factor receptor is inappropriately expressed exhibit reduced pheromone signaling, a phenomenon termed receptor inhibition. In cells undergoing receptor inhibition, activation of the signaling pathway occurs normally at early time points but decreases after prolonged exposure to pheromone. Mutations that suppress the effects of receptor inhibition were obtained in the STE4 gene, which encodes the beta-subunit of the G protein that transmits the pheromone response signal. These mutations mapped to the N terminus and second WD repeat of Ste4p in regions that are not part of its Galpha binding surface. A STE4 allele containing several of these mutations, called STE4(SD13), reversed the signaling defect seen at late times in cells undergoing receptor inhibition but had no effect on the basal activity of the pathway. Moreover, the signaling properties of STE4(SD13) were indistinguishable from those of STE4 in wild-type MATa and MATalpha cells. These results demonstrate that the effect of the STE4(SD13) allele is specific to the receptor inhibition function of STE4. STE4(SD13) suppressed the signaling defect conferred by receptor inhibition in a MATa strain containing a deletion of GPA1, the G protein alpha-subunit gene; however, STE4(SD13) had no effect in a MATalpha strain containing a GPA1 deletion. Suppression of receptor inhibition by STE4(SD13) in a MATa strain containing a GPA1 deletion was unaffected by deletion of STE2, the alpha-factor receptor gene. The results presented here are consistent with a model in which an a-specific gene product other than Ste2p detects the presence of the a-factor receptor and blocks signaling by inhibiting the function of Ste4p.

Amino Acid Sequence↗

The Wilms' tumor suppressor gene (wt1) product regulates Dax-1 gene expression during gonadal differentiation.

Gonadal differentiation is dependent upon a molecular cascade responsible for ovarian or testicular development from the bipotential gonadal ridge. Genetic analysis has implicated a number of gene products essential for this process, which include Sry, WT1, SF-1, and DAX-1. We have sought to better define the role of WT1 in this process by identifying downstream targets of WT1 during normal gonadal development. We have noticed that in the developing murine gonadal ridge, wt1 expression precedes expression of Dax-1, a nuclear receptor gene. We document here that the spatial distribution profiles of both proteins in the developing gonad overlap. We also demonstrate that WT1 can activate the Dax-1 promoter. Footprinting analysis, transient transfections, promoter mutagenesis, and mobility shift assays suggest that WT1 regulates Dax-1 via GC-rich binding sites found upstream of the Dax-1 TATA box. We show that two WT1-interacting proteins, the product of a Denys-Drash syndrome allele of wt1 and prostate apoptosis response-4 protein, inhibit WT1-mediated transactivation of Dax-1. In addition, we demonstrate that WT1 can activate the endogenous Dax-1 promoter. Our results indicate that the WT1-DAX-1 pathway is an early event in the process of mammalian sex determination.

Animals↗