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Biomedical subjects

H Kim

Publications and source records attributed to H Kim.

At least 685 records · Page 38Linked to original sources
PubMed1994

CD44 expression in colorectal adenomas is an early event occurring prior to K-ras and p53 gene mutation.

Neoplastic progression of colorectal epithelial cells from benign adenomas to malignant carcinomas appears to result from a series of genetic alterations involving both oncogenes and tumor suppressor genes. This progression was recently found to be associated with expression of splice variant isoforms of CD44, a cell surface hyaluronate receptor implicated in carcinogenesis. In this study we examined the relationship of CD44 expression to somatic genetic events in the adenoma-carcinoma sequence: point mutation of K-ras in codons 12 and 13 and overexpression of p53 protein as a marker of gene mutation. Among 22 small adenomas, CD44 was present in 9 (41%), of which only 1 contained a K-ras mutation. CD44 was absent in the other 2 small adenomas positive for K-ras mutation or p53 overexpression. In contrast to the early expression of CD44 in small adenomas, mutations of K-ras and p53 were detected preferentially in large adenomas and late-stage adenomas containing carcinoma. The frequent expression of CD44 prior to K-ras and p53 gene alterations in colorectal neoplasia suggests that activation of CD44 gene expression is related to earlier events in the adenoma-carcinoma sequence, possibly cell activation and proliferation following APC gene mutation or alteration of DNA methylation.

Adenoma↗
PubMed1994

Gas chromatographic and high-performance liquid chromatographic methods for the determination of genaconazole in biological fluids.

Gas chromatographic (GC) and high-performance liquid chromatographic (HPLC) methods were developed for the determination of genaconazole in biological fluids. Both methods involved organic solvent extraction followed by solid-phase extraction on a C18 column. GC analysis utilized a megabore column (DB-17) with 63Ni electron-capture detection, whereas HPLC analysis utilized separation on a reversed-phase column with a methanol-phosphate buffer mixture as the mobile phase and quantitation by UV absorbance at 208 nm. Both methods yielded good linearity, accuracy and precision. The limit of quantitation (LOQ) was 0.025 microgram per ml of serum for GC and 0.2 microgram per ml of serum or 0.5 microgram per ml of urine for HPLC analysis. Both GC and HPLC methods were used for the determination of serum concentration-time curves of genaconazole in man following oral administration of a 50-mg dose.

Antifungal Agents↗
PubMed1994

O-glycosylation in hinge region of mouse immunoglobulin G2b.

Mouse monoclonal immunoglobulin G2b (IgG2b) antibodies are known to contain two forms of the heavy chain that are different in susceptibility to the protease attack. In the present study, by use of an affinity column containing sialic acid-binding lectins from Maackia amurensis seeds, a mouse monoclonal IgG2b was successfully separated into three phenotypes, which are different in the degree of sialylation in the heavy chain. In the N-linked oligosaccharides from all of the IgG2b phenotypes, virtually no sialylation was detected. Elution profiles of the lysyl endopeptidase digestion products were compared for the three phenotypes. The peptides eluted at different retention times were subjected to fast atom bombardment-mass spectrometry and amino acid sequence analyses. It was revealed that approximately 40% of the heavy chain of the mouse IgG2b are O-glycosylated at Thr-221A in the hinge region, predominantly with a tetrasaccharide composed of GalNAc, Gal, and two N-glycolylneuraminic acid residues. We suggest that the O-glycosylation renders the hinge region resistant against the proteolyses of the heavy chain. A therapeutic significance of the O-glycosylation of IgG2b is briefly discussed.

Amino Acid Sequence↗
PubMed1994

Correlates of mortality in Russian and US women. The Lipid Research Clinics Program.

Associations between selected risk factors and 7-year all-cause mortality were studied in 2,187 Russian women and 2,146 US women who were screened as part of a US-Russian collaborative program. The US women were screened during the period 1972-1976, while the Russian women were screened from 1978 to 1982. Cigarette smoking and elevated systolic blood pressure were associated with increased mortality in both samples. High density lipoprotein (HDL) cholesterol was inversely related to mortality in US women, but there was no association of HDL cholesterol with mortality in Russian women. Prevalent angina and electrocardiographic abnormalities were associated with mortality in both samples, but the relations achieved statistical significance only in the Russian sample. The problems of cigarette smoking and elevated blood pressure should be addressed with public health measures in both countries. The absence of an association between HDL cholesterol and mortality in the Russian sample should be investigated further.

Adult↗
PubMed1994

D-ribose stabilizes precursor and mature ribose-binding proteins of Escherichia coli.

Heat- and guanidine hydrochloride-induced unfolding and refolding of precursor as well as mature ribose-binding proteins of Escherichia coli were studied in the presence of D-ribose using intrinsic tyrosine fluorescence and circular dichroism. The precursor and mature proteins have shown virtually identical unfolding-folding behavior. It was observed that D-ribose refolds partially unfolded precursor and mature ribose binding proteins into native structure and decreases the unfolding rate of the these proteins. The conformational stabilities of these proteins were found to increase with increasing D-ribose concentration.

Carrier Proteins↗
PubMed1994

Dynamical structure of the hinge region of immunoglobulin G as studied by 13C nuclear magnetic resonance spectroscopy.

The segmental flexibility of the hinge region of immunoglobulin G (IgG) molecules has been considered to play important roles in the mediation between antigen recognition and effector functions. Here we report the result of a 13C nuclear magnetic resonance study of the dynamical structure of the hinge region of a mouse monoclonal IgG2a antibody. In the present work, a variety of IgG2a analogs selectively labeled with 13C at the carbonyl carbon atom were prepared. The flexibility of the hinge region was discussed on the basis of the linewidth data of 13C resonances obtained using a Carr-Purcell-Meiboom-Gill pulse train. It was concluded that the hinge region of the mouse IgG2a molecule has a mosaic structure with heterogeneous nature of flexibility with the rigid core part flanked by upper and lower hinges, which are highly flexible peptide segments. Cleavage of the inter-chain disulfide bridges led to homogeneous flexibility of the hinge region, except for the N-terminal side of the upper hinge. It was suggested that the rigidity in the N-terminal side of the upper hinge is due to the interaction with the CH1 domain. Biological significance of the mosaic structure of the hinge region was briefly discussed.

Amino Acid Sequence↗
PubMed1994

Radiation therapy for stage I and IIA testicular seminoma.

PURPOSE: To review the survival, cure rate, treatment morbidity, and late sequelae of histologically confirmed seminoma patients who underwent orchiectomy and radiation therapy at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, from 1964 to 1988. METHODS AND MATERIALS: There were 128 patients, with a median patient age of 37 years (range, 17-79 years). Follow-up ranged from 1-24 years, with a median of 6.7 years. There were 95 patients with Stage I and 33 with Stage IIA disease. All patients were treated with orchiectomy followed by iliac and paraaortic irradiation (median tumor dose: 2500 cGy for Stage I and 3400 cGy for Stage IIA patients). Twenty-five of 33 patients with Stage IIA disease received prophylactic mediastinal and left supraclavicular irradiation (median dose, 2700 cGy). RESULTS: For patients with Stage I disease, 5-year disease-free survival, overall survival, and survival corrected for intercurrent disease were 97%, 100%, and 100%, respectively. For patients with Stage IIA disease, the 5-year disease-free survival, overall survival, and survival corrected for intercurrent disease were 93%, 89%, and 97%, respectively. Four patients (3%) had recurrences; all were outside the radiation treatment field. Three of four were successfully salvaged with chemotherapy and rendered disease-free; the other patient refused treatment. There were no mediastinal recurrences whether prophylactic mediastinal irradiation was administered or not. Bowel obstruction and necrosis developed in one patient who received 3363 cGy midplane dose to the pelvic and paraaortic areas as well as additional intraperitoneal colloidal 198Au (150 mCi) for a ruptured seminoma from an undescended testis. CONCLUSION: In summary, radical orchiectomy and irradiation of the iliac and paraaortic lymphatics is the treatment of choice for patients with Stage I and IIA testicular seminoma.

Adolescent↗
PubMed1994

Propagation of mouse and human T cells with defined antigen specificity and function.

Difficulties maintaining fully functional CD4+ T cells in culture have historically limited the study of their role in tumour rejection as well as other clinical applications. As the therapeutic value of current antitumour CD8+ T cell adoptive therapy becomes better defined, a strong impetus exists to determine optimal conditions for culturing antitumour CD4+ T cells. Our goal is to promote broadly polyclonal, antigen-specific CD4+ T cell responses of either Th1 or Th2 character for use in antitumour therapy or allograft facilitation, respectively. Similar obstacles exist in murine and human cultures: (1) during even brief periods of culture CD4+ T cells develop high 'background' reactivity to class II-positive antigen-presenting cells; (2) maintenance of antigen specificity as evidenced by cytokine secretion and short-term proliferation assays is insufficient to ensure bulk numerical expansion; (3) Th1-type CD4+ T cells often lose their potential for antigen-specific secretion of interleukin 2 on re-stimulation (though remain inducible by 12-O-tetradecanoylphorbol 13-acetate/ionomycin); (4) during prolonged culture selection pressure favours CD4+ subpopulations that recognize artifactual antigens such as culture medium proteins; (5) even with optimal culture conditions, cultured CD4+ T cells may function differently in vivo to uncultured CD4+ T cells. We have devised various strategies to surmount these obstacles by use of selected cytokines, antigen-presenting cells and timely culture manoeuvres.

Animals↗
PubMed1994

Caenorhabditis elegans sqt-3 mutants have mutations in the col-1 collagen gene.

sqt-3 mutants of Caenorhabditis elegans form dumpy larvae and adults and display allele-specific defects in locomotion, fertility, and viability. We have determined that the sqt-3 locus encodes COL-1 collagen. We physically mapped the col-1 gene to a cosmid on chromosome V whose position is consistent with the location of the sqt-3 gene. We also observed morphological defects in sqt-3 mutants at stages that correlate with the mRNA expression patterns of col-1. Sequence analysis of the col-1 gene in the three temperature-sensitive mutants revealed that each allele of sqt-3 has a unique missense mutation causing arginine or glutamic acid to replace glycine in a Gly-X-Y triple helical domain. These glycine substitutions may result in longer non-collagenous domains, which may decrease the thermal stability or impart additional flexibility to mutant trimers. In addition, we describe four corrections to the published sequence of col-1, including one fifteen nucleotide addition that completes a conserved domain in the amino terminal coding region.

Alleles↗
PubMed1994

Protein crystallography and infectious diseases.

The current rapid growth in the number of known 3-dimensional protein structures is producing a database of structures that is increasingly useful as a starting point for the development of new medically relevant molecules such as drugs, therapeutic proteins, and vaccines. This development is beautifully illustrated in the recent book, Protein structure: New approaches to disease and therapy (Perutz, 1992). There is a great and growing promise for the design of molecules for the treatment or prevention of a wide variety of diseases, an endeavor made possible by the insights derived from the structure and function of crucial proteins from pathogenic organisms and from man. We present here 2 illustrations of structure-based drug design. The first is the prospect of developing antitrypanosomal drugs based on crystallographic, ligand-binding, and molecular modeling studies of glycolytic glycosomal enzymes from Trypanosomatidae. These unicellular organisms are responsible for several tropical diseases, including African and American trypanosomiases, as well as various forms of leishmaniasis. Because the target enzymes are also present in the human host, this project is a pioneering study in selective design. The second illustrative case is the prospect of designing anti-cholera drugs based on detailed analysis of the structure of cholera toxin and the closely related Escherichia coli heat-labile enterotoxin. Such potential drugs can be targeted either at inhibiting the toxin's receptor binding site or at blocking the toxin's intracellular catalytic activity. Study of the Vibrio cholerae and E. coli toxins serves at the same time as an example of a general approach to structure-based vaccine design. These toxins exhibit a remarkable ability to stimulate the mucosal immune system, and early results have suggested that this property can be maintained by engineered fusion proteins based on the native toxin structure. The challenge is thus to incorporate selected epitopes from foreign pathogens into the native framework of the toxin such that crucial features of both the epitope and the toxin are maintained. That is, the modified toxin must continue to evoke a strong mucosal immune response, and this response must be directed against an epitope conformation characteristic of the original pathogen.

Amino Acid Sequence↗
PubMed1994

NAD glycohydrolases: a possible function in calcium homeostasis.

NAD glycohydrolases are the longest known enzymes that catalyze ADP-ribose transfer. The function of these ubiquitous, membrane-bound enzymes has been a long standing puzzle. The NAD glycohydrolases are briefly reviewed in light of the discovery by our laboratory that NAD glycohydrolases are bifunctional enzymes that can catalyze both the synthesis and hydrolysis of cyclic ADP-ribose, a putative second messenger of calcium homeostasis.

Animals↗
PubMed1994

Intussusception: characteristic radiolucencies on the abdominal radiograph.

Six hundred and twenty-five sets of supine and erect abdominal radiographs of 288 patients with the confirmed diagnosis of intussusception (315 episodes) and 310 patients without intussusception were reviewed retrospectively to determine the characteristic radiographic features of intussusception. Among the patients with intussusception, 155 episodes (49%) showed a soft tissue mass and nearly half of these (71) showed characteristic radiolucencies (target, crescentic, or amorphous) in the soft tissue mass. Thirty-five episodes showed the radiolucencies on both the supine and erect radiographs; in 16 cases the type of radiolucency differed on the two films. In patients without intussusception, abnormal radiolucencies were seen in only seven cases (2.3%). Computed tomography performed prospectively in five patients showed the radiolucencies in the soft tissue mass to be intussuscepted mesenteric fat. We conclude that abnormal radiolucencies in the soft tissue mass on plain radiographs are characteristic of intussusception.

Adolescent↗
PubMed1994

Comprehensive quality management program for radiation oncology.

A quality management program for both external beam irradiation (electron and photon modes) and brachytherapy (high dose rate (HDR) and low dose rate (LDR) has been developed. The program follows current USA federal regulations for therapeutic administration of by-product materials. After implementation of the program, 54 HDR patients, 36 LDR brachytherapy patients and 311 external beam patients (including 30 stereotactic radiosurgery cases) were treated. The results of this program are presented.

Brachytherapy↗