Biomedical subjects

H L Kim

Publications and source records attributed to H L Kim.

At least 19 recordsLinked to original sources

PubMed2003

Association of the CD14 gene -159C polymorphism with progression of IgA nephropathy.

The risk factors associated with the progression of IgA nephropathy (IgAN), the most common form of glomerulonephritis, are unclear. It has been suggested that CD14 signalling in response to various microbes affects the natural history of chronic inflammatory conditions. It has been hypothesised that variants in the promoter region of the CD14 gene might alter the expression of CD14, and this in turn could influence the progressive nature of IgAN. PCR-RFLP was used to determine the polymorphism at the -159 site (T to C). The distribution of the CD14/-159 polymorphism was no different in patients with IgAN (n=216) compared to 171 healthy controls. After follow up for 86 months, it was found that an excess of the C genotype occurred in patients with progressive disease (p=0.03) and the risk of disease progression increased as the number of C alleles increased (p for trend = 0.002). The hazard ratio for progression in the patients with the CC genotype was 3.2 (p=0.025) compared with the patients possessing the TT genotype. After LPS stimulation, sCD14 was released more abundantly from the PBMCs of the TT subjects than from that of the CC subjects (p=0.006), even though mCD14 expression level was no different. In addition, the TT subjects released less IL-6 than the CC subjects after stimulation (p=0.0003). These results suggest that the CD14/-159 polymorphism is an important marker for the progression of IgAN and may modulate the level of the inflammatory responses.

Adult↗

PubMed2002

Interdependent effect of angiotensin-converting enzyme and platelet-activating factor acetylhydrolase gene polymorphisms on the progression of immunoglobulin A nephropathy.

In order to investigate the interdependent action of the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene and polymorphism in exon 11 (C1136-->T; Ala379Val) of the platelet-activating factor acetylhydrolase (PAF-AH) gene, which encodes a functional antagonist of PAF, on the progression of immunoglobulin A (IgA) nephropathy, we analysed both polymorphisms in patients with primary IgA nephropathy, who were followed-up for longer than 3 years. During the follow-up (87.3 +/- 50.0 months), the disease progressed in 38 of the 191 patients (19.9%). The D allele of the ACE gene in the absence of the T allele of the PAF-AH gene did not affect the prognosis [odds ratio (OR), 3.6; 95% confidence interval (CI), 0.8-16.4] and neither did the T allele in the absence of the D allele (OR, 3.0; 95% CI, 0.4-24.2). However, the presence of both was a significant prognostic factor (OR, 6.6; 95% CI, 1.4-31.3). After adjusting for other risk factors, the presence of both proved to be an independent risk factor (OR, 4.5; 95% CI, 1.6-12.7). These results suggest that the interdependent effects of ACE and PAF-AH polymorphisms on the progression of IgA nephropathy might be more important than the effect of the individual polymorphisms.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2001

Cleavage of purified neuronal clathrin assembly protein (CALM) by caspase 3 and calpain.

The most efficient means of protein internalization from the membrane are through clathrin-coated pits, which concentrate protein interactions with the clathrin-associated assembly protein complex AP-2 and internalization signals in the cytoplasmic domain of transmembrane proteins. Binding of clathrin assembly protein to clathrin triskelia induces their assembly into clathrin-coated vesicles (CCVs). Due to a difficulty of isolating clathrin molecules from their complex or assembly state in the cells, most of the studies were carried out with recombinant clathrin proteins, which may present different conformation and structural variation. In this study, we have developed an efficient method of isolating the native clathrin assembly protein lymphoid myeloid (CALM) from the bovine brain that is enriched with clathrin and clathrin associated proteins and characterized by their sensitivity to proteases and it's ability to form CCV. The purified CALM has molecular weight of approximately 100,000 dalton on SDS-PAGE, which is consistent with the result of in vitro translation. The purified CALM protein could promote the assembly of clathrin triskelia into clathrin cage, and cleaved CALM proteolysed by caspase 3 and calpain could not promote them. In this respect, our data support a model in which CALM functions like AP180 as a monomeric clathrin assembly protein and might take part in apoptotic process in neuronal cells.

Adaptor Proteins, Vesicular Transport↗

PubMed2001

Cell-free expression and functional reconstitution of CALM in clathrin assembly.

Clathrin-mediated vesicle formation is an essential step in the intracellular trafficking of the protein and lipid. Binding of clathrin assembly protein to clathrin triskelia induces their assembly into clathrin-coated vesicles (CCVs). In order to better understand a possible role of post-translational modification of CALM (clathrin assembly protein lymphoid myeloid), the homologue of AP180, in the assembly of CCVs, CALM was expressed in the cell-free reticulocyte translation system that is capable of carrying out post-translational modification. The apparent molecular weight of the expressed recombinant CALM was estimated as 105 kD. Alkaline phosphatase treatment of CALM resulted in a mobility shift on SDS-PAGE. We found that CALM was associated with the proteins harboring SH3 domain, promote assembly of clathrin triskelia into clathrin cage and bound to the preformed clathrin cage. CALM was also proteolyzed by caspase 3 and calpain but not by caspase 8. These results indicated that the post-translationally modified CALM, expressed in the eukaryotic cell-free reticulocyte translation system was able to mediate the assembly of clathrin and the coated-vesicle formation.

Adaptor Proteins, Vesicular Transport↗

PubMed2001

Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancers.

We have shown recently (B. A. Yoshida et al., Cancer Res., 59: 5483-5487) that mitogen-activated protein kinase kinase 4 (MKK4) can suppress AT6.1 rat prostate cancer metastases in vivo. Evaluation of the expression of components of the MKK4 signaling cascade showed a loss or down-regulation of expression of MKK4 or c-Jun, a downstream mediator of MKK4, in six of eight human prostate cancer cell lines. Given these findings, we next assessed whether MKK4 dysregulation occurs during the development of clinical prostate cancer. Immunohistochemical studies showed high levels of MKK4 expression in the epithelial but not the stromal compartment of normal prostatic tissues. In neoplastic tissues, a statistically significant, direct, inverse relationship between Gleason pattern and MKK4 was established. These results demonstrate that MKK4 protein is consistently down-regulated during prostate cancer progression and support a role for dysregulation of its signaling cascade in clinical disease. To test the possibility that down-regulation of MKK4 protein is the result of allelic loss, metastatic prostate cancer lesions were examined for loss of heterozygosity (LOH) within the MKK4 locus (D17S969). These studies showed a 31% (5 of 16) LOH of MKK4 that is not associated with coding region mutations, which suggests that the nucleotide sequence of the gene in the remaining allele is infrequently mutated.

Enzyme Activation↗

PubMed2001

Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel.

Calcium influx through N-type calcium channels mediates synaptic transmission at numerous central synapses and transduces nociceptive information in the spinal dorsal horn. However, the precise role of N-type calcium channels in pain perception is not fully elucidated. To address this issue, we generated and analyzed knockout mice for alpha(1B,) the pore-forming subunit of the N-type calcium channel. Homozygous mutants are viable, fertile, and show normal motor coordination. In small-diameter dorsal root ganglion neurons from mutants the density of calcium channel currents is significantly reduced, which can be accounted for by the abolition of N-type currents. We performed several pain-related behavioral tests using the mutant mice. alpha(1B)-Deficient mice show reduced response to mechanical stimuli in the von Frey test and increased tail flick latency in response to radiant heat, indicating altered spinal reflexes. However, pain response in the hot plate test is normal. In the formalin paw test, the mutant mice exhibit significantly attenuated response in Phase 2, but normal pain behaviors in Phase 1. The response to visceral inflammatory pain caused by acetic acid is also reduced in alpha(1B) knockout mice. These results suggest that the alpha(1B) subunit of N-type calcium channel plays a major role in pain perception by acting at the spinal level, but not at the supraspinal level.

Animals↗

PubMed2001

Does the CaverMap device help preserve potency?

Erectile dysfunction remains a common complication following radical prostatectomy. The CaverMap Surgical Aid (UroMed, Boston, MA) was designed to aid the surgeon in identifying and preserving neurovascular bundles (NVBs). However, the size of the CaverMap nerve stimulator may make it difficult to trace the cavernous nerves before the prostate is removed, particularly in obese men or in patients who have a large prostate or a narrow pelvis. In a randomized, controlled study, the use of the CaverMap during radical prostatectomy resulted in improved nocturnal erections, but did not lead to improved overall sexual function. The CaverMap device, however, may be useful as a research tool in that it helps determine whether the NVBs have been successfully preserved after removing the prostate. However, preservation of the NVB does not guarantee recovery of potency, which may be prolonged despite successful stimulation of the cavernous nerves intraoperatively. This suggests that erectile dysfunction following radical prostatectomy is multifactorial.

Erectile Dysfunction↗

PubMed2001

Practice patterns in the treatment of female urinary incontinence: a postal and internet survey.

OBJECTIVES: To survey American urologists to assess practice patterns in treating female incontinence. Advances in the treatment of female incontinence have changed the way urologists practice. METHODS: Postal and e-mail surveys were sent to 2502 members of the American Urological Association. RESULTS: From the postal group (n = 1000), 419 (42%) responses were obtained; from the e-mail group (n = 1502), 160 (11%) responses were obtained. For types I, II, and III stress urinary incontinence (SUI), 239 (44%) of 546, 388 (68%) of 570, and 512 (94%) of 547 urologists, respectively, recommended a sling procedure. For type I SUI, 75 (53%) of the 143 respondents in practice for less than 10 years recommended a sling procedure. The sling was recommended by 62 (35%) of the 176 respondents in practice for longer than 20 years (P <0.001). Most urologists (75%, 358 of 480) referred patients with significant vaginal prolapse to a gynecologist; however, urologists in full-time academic practice were more likely to offer surgical treatment (56%, 29 of 52). Most urologists recommended medical treatment for urge incontinence (94%, 461 of 491), and the medications most commonly selected were tolterodine (41%, 202 of 491), oxybutynin (26%, 129 of 491), and extended-release oxybutynin (25%, 125 of 491). CONCLUSIONS: Overall, a sling procedure was the most commonly recommended surgical procedure for all types of SUI. Most urologists referred patients with significant vaginal prolapse to a gynecologist. For type I SUI, older urologists were more likely than younger urologists to perform needle bladder neck suspension.

Female↗

PubMed2001

Correlation between biopsy and radical cystectomy in assessing grade and depth of invasion in bladder urothelial carcinoma.

OBJECTIVES: To assess the degree of correlation between the pathologic characteristics of the specimens obtained from biopsy and radical cystoprostatectomy. The stage and grade of bladder urothelial (transitional cell) carcinoma are important predictors of prognosis. METHODS: We retrospectively identified 169 cases of urothelial carcinoma from 222 radical cystectomies performed at University of Chicago Hospitals from 1992 to 1999. RESULTS: For all the cases in this study, the histologic grade, using the 1998 World Health Organization and International Society of Urological Pathologists (WHO/ISUP) classification, was identical when the biopsy specimen and radical cystectomy specimen were compared. However, when the same cases were assessed using the traditional three-grade system, the histologic grade increased or decreased by one grade in 19 (11%) and 8 (5%) of 169 cases, respectively. Patients with invasion of the lamina propria on biopsy had tumor extending outside the bladder in 15 (27%) of 55 cases. Patients with invasion of the muscularis propria on biopsy had tumor extending outside the bladder in 47 (49%) of 96 cases, including nodal metastasis in 22 (23%) of 96 cases. Overall, bladder biopsy underestimated the true extent of the disease in 78 (46%) of 169 cases. CONCLUSIONS: Using either the WHO/ISUP (1998) classification or the traditional three-grade system, the histologic grade of the biopsy specimen is a fairly good predictor of the final histologic grade. The preoperative biopsy tends to understage bladder cancer. Patients with muscularis propria invasion demonstrated by biopsy have a significantly higher risk of non-organ-confined disease than those with lamina propria invasion.

Aged↗

PubMed2001

Complications of cystectomy in patients with a history of pelvic radiation.

OBJECTIVES: To compare the complications occurring during the first year of follow-up after radical cystectomy in two groups, one with and one without a history of pelvic radiation. Radical cystectomy and urinary diversion is the treatment of choice for invasive bladder cancer. METHODS: One hundred ninety-four cystectomies were performed between January 1995 and June 2000 by a single surgeon. Twenty-three patients were identified with a history of external beam radiotherapy to the pelvis (EBRT group), and 23 additional patients without a history of pelvic radiation were randomly selected to serve as the control group. RESULTS: Although the overall risk of having a complication was not statistically different in the EBRT group (48%) than in the control group (30%; P = 0.183), complications directly related to surgery were higher in the EBRT group than in the control group (48% versus 26%; P = 0.045). The patients in the EBRT group were more likely to require an invasive procedure (39% versus 9%; P = 0.018). In addition, 5 (22%) of 23 patients in the EBRT group had a symptomatic fluid collection, which was diagnosed as a urine leak (n = 2) or an abdominal abscess (n = 3). In contrast, no patient in the control group developed a symptomatic fluid collection. CONCLUSIONS: Cystectomy after pelvic radiation is associated with acceptable morbidity; however, compared with cystectomy performed in a nonirradiated pelvis, the risk of complications that will require invasive intervention is increased. A history of prior pelvic radiation significantly increases the risk of a symptomatic fluid collection.

Aged↗

PubMed2001

Comparison of the durability of cadaveric and autologous fascia using an in vivo model.

OBJECTIVES: To assess the durability of both autologous and cadaveric fascia using an animal model. The pubovaginal sling procedure can be performed using autologous, cadaveric, or synthetic materials. Few data are available about the strength and durability of these materials. METHODS: Rectus abdominus fascia harvested from 6 female Sprague-Dawley rats was processed by Tutogen Medical. In 20 female Sprague-Dawley rats, three different types of fascia were implanted subcutaneously into each animal: autologous rectus abdominus fascia harvested at the time of surgery; rat cadaveric fascia processed by Tutogen; and human cadaveric fascia (Tutogen). The rats were killed at 2 months (10 rats) and 4 months (10 rats) after implantation. The mechanical properties of the tissue were assessed using the trouser tear test, and the fracture toughness was calculated. RESULTS: Compared with the fracture toughness before implantation, the implanted rat autologous fascia decreased in toughness from 1763 to 1243 J/m(2) (P = 0.12), the implanted rat cadaveric fascia decreased in toughness from 1539 to 1022 J/m(2) (P = 0.02), and the implanted human cadaveric fascia decreased in toughness from 2120 to 1145 J/m(2) (P = 0.09). The fracture toughness of the implanted rat cadaveric fascia and rat autologous fascia did not differ significantly (P = 0.29). CONCLUSIONS: The changes in strength or elasticity can be detected using the trouser tear test to calculate the fracture toughness. Both cadaveric and autologous fascial grafts may decrease in toughness with time. The long-term durability of the graft may only be a minor factor in determining the success of the pubovaginal sling procedure.

Animals↗

PubMed2001

Apoptosis and megakaryocytic differentiation during ex vivo expansion of human cord blood CD34+ cells using thrombopoietin.

Thrombopoietin (TPO), the primary regulator of megakaryocytopoiesis, plays important roles in early haematopoiesis. Previously, we have demonstrated that TPO induces a characteristic pattern of apoptosis during ex vivo expansion of cord blood (CB) CD34+ cells. In this study, we have demonstrated that the TPO-induced apoptotic cells belong to the megakaryocytic (MK) lineage and that initially expanding MK progenitors declined along with the appearance of TPO-induced apoptosis. Human CB CD34+ cells were expanded in serum-free conditions with TPO. Multidimensional flow cytometry using simultaneous measurement of apoptosis and immunophenotyping showed that the TPO-induced apoptotic cells appeared in CD61+ fractions. Immunocytochemical analysis of the fluorescent activated cell-sorted fractions showed that the apoptosis-associated CD44low fraction expressed CD61. Clonogenic assay revealed 7.4 +/- 0.50-fold increase of total megakaryocyte colony-forming units (CFU-MKs) during the initial 9 d. Thereafter, the number of CFU-MKs decreased in parallel with the increase of apoptosis. When the MK colonies were subdivided according to size, the proportion of large colonies progressively decreased, while that of medium and small colonies increased. In particular, from d 6 small colonies became predominant. These results suggested that the MK progenitors matured as they expanded during ex vivo expansion with TPO and then proceeded to apoptosis.

Antigens, CD↗

PubMed2001

Requirement for the L-type Ca(2+) channel alpha(1D) subunit in postnatal pancreatic beta cell generation.

Pancreatic beta cells are the source of insulin, which directly lowers blood glucose levels in the body. Our analyses of alpha(1D) gene-knockout (alpha(1D)(-/-)) mice show that the L-type calcium channel, alpha(1D), is required for proper beta cell generation in the postnatal pancreas. Knockout mice were characteristically slightly smaller than their littermates and exhibited hypoinsulinemia and glucose intolerance. However, isolated alpha(1D)(-/-) islets persisted in glucose sensing and insulin secretion, with compensatory overexpression of another L-type channel gene, alpha(1C). Histologically, newborn alpha(1D)(-/-) mice had an equivalent number of islets to wild-type mice. In contrast, adult alpha(1D)(-/-) mice showed a decrease in the number and size of islets, compared with littermate wild-type mice due to a decrease in beta cell generation. TUNEL staining showed that there was no increase in cell death in alpha(1D)(-/-) islets, and a 5-bromo-2' deoxyuridine-labeling (BrdU-labeling) assay illustrated significant reduction in the proliferation rate of beta cells in alpha(1D)(-/-) islets.

Animals↗

PubMed2001

Differential expression of various cytokine and chemokine genes between proliferative and non-proliferative glomerulonephritides.

BACKGROUND: Intraglomerular cellular proliferation is one of the major determinants for dividing various glomerulonephritis (GN) into two groups, such as proliferative versus non-proliferative. Cytokines and chemokines are involved in the pathogenetic pathways and would affect the functional and histologic sequelae. We hypothesized that the morphological difference might be based on the differential intrarenal expression of various cytokines and chemokines. We quantified the intrarenal gene expression of various cytokines and chemokines, and correlated it with clinical parameters. METHODS: Total RNA was extracted from 54 proliferative GN (PGN) core biopsy specimens and 42 non-proliferative GN (NPGN) specimens. Using the internal competitors, RT-PCR was instituted to quantify mRNAs. RESULTS: The magnitude of the gene expressions of IL-2, IFN-gamma, and IFN-gamma/IL-10 ratio were significantly higher in PGN than in NPGN. RANTES and IL-8 had more abundant gene messages in PGN. It was shown that Th1 cytokine was upregulated if GN was mediated by immune complexes regardless of cellular proliferation. But chemokines had the elevated levels of expression in PGN among immune complex-mediated GN. Up-regulation of the IFN-gamma/IL-10 ratio and TNF-alpha was associated with poor renal function at the time of biopsy. Renal tissues from the patients with a non-nephrotic range of proteinuria showed abundant messages for proinflammatory cytokines and chemokines. CONCLUSION: Th1, proinflammatory cytokines, and chemokines were more abundant in proliferative GN, and correlated with unfavorable clinical parameters. We propose that the clinical manifestations and diverse histologic features of human GN are associated with differential expressions of specific cytokines and chemokines.

Adolescent↗

PubMed2001

Results of treatment with tamsulosin in men with acute urinary retention.

PURPOSE: The aim of this study was to prospectively assess the outcome in men treated with temporary catheter drainage and tamsulosin after an episode of acute urinary retention (AUR). MATERIALS AND METHODS: Thirty-three consecutive men with AUR were treated with tamsulosin 0.4 mg daily for at least 4 days before a trial of voiding. Those men who were able to void adequately continued taking tamsulosin and were evaluated at 2-week and 3-month follow-up. After 3 months, additional follow-up was obtained at regular intervals as determined by the treating physician. RESULTS: Median follow-up was 6.5 months. Mean urine volume at the time of initial bladder drainage was 790 mL. Eighty-eight percent (29/33) of men were able to void initially. Transurethral prostatectomy or intermittent catheterization were necessary in 9 (27%) of 33 patients during the follow-up period. A poor quality-of-life score on the initial International Prostate Symptom Score (p = .038) and a high postvoid residual volume 2 weeks after catheter removal (p = .013) correlated with failure of medical therapy. Patients with AUR after nonurologic surgery had a significantly better outcome than those with AUR that did not occur postoperatively. Mean symptom score, quality-of-life score, and postvoid residual urine volume were 12.9, 2.7, and 111 mL, respectively, at 2-week follow-up and were 11.9, 2.8, and 61.7 mL, respectively, at 3-month follow-up. Mean peak urinary flow rate at 3 months was 7.7 mL/s. CONCLUSIONS: Tamsulosin appears to be helpful in the management of men with AUR. The majority of men were able to avoid surgery after temporary catheter drainage.

Acute Disease↗

PubMed2000

Purification of clathrin assembly protein from rat liver.

Recently, the gene encoding clathrin assembly protein of lymphoid myeloid leukemia (CALM), which is homologous to the AP180, was cloned from rat brain, and its expression differential to AP180 was reported (Kim and Lee, 1999). This gene product promotes the polymerization of clathrin into clathrin cage and found to be a regulator in membrane trafficking between intracellular compartments in eukaryotic cells (Kim et al., 2000). In this study, we have purified the CALM protein from clathrin-coated vesicles of rat liver using the monoclonal antibody against the recombinant N-terminal region of the CALM. The coated proteins extracted from the coated vesicle fraction was further purified by multi-step procedures involving gel-filtration and ion-exchange chromatography and SDS-PAGE. The purified protein with an apparent molecular weight of 100 kD promoted the assembly of clathrin triskelia into clathrin cage. In this respect the CALM protein bears a functional resemblance to the AP180 that has been previously described.

Adaptor Proteins, Vesicular Transport↗

PubMed2000

Use of new technology in endourology and laparoscopy by american urologists: internet and postal survey.

OBJECTIVES: To assess the use of new technology by American urologists. METHODS: Using the American Urological Association directory, surveys were sent via the U.S. postal service to 1000 randomly selected American urologists and 3065 urologists who had an Internet address listed in the directory. RESULTS: Responses were received from 601 urologists (415 postal, 186 Internet). Overall, 81% of survey respondents reported performing fewer or the same number of percutaneous procedures as compared with 3 to 4 years ago and 84% reported carrying out more or the same number of ureteroscopic procedures in the treatment of patients with stone disease. Open dismembered pyeloplasty (43%) and Acucise endopyelotomy (42%) were most frequently reported as the preferred treatment for adult patients with symptomatic ureteropelvic junction obstruction. Although 60% of respondents reported that they have taken a laparoscopy course, 67% currently do not perform any laparoscopy in their practice. In addition, only 7% of urologists stated that laparoscopy comprises more than 5% of their practice. When stratified by the number of years in practice, those in practice less than 10 years were more likely than those in practice 10 to 20 years and those in practice longer than 20 years to have performed an endopyelotomy (77%, 60%, and 48%, respectively, P <0.001) and to be currently performing laparoscopy (49%, 36%, and 18%, respectively, P <0.001). CONCLUSIONS: Compared with 3 to 4 years ago, American urologists are performing more ureteroscopy and fewer percutaneous stone procedures. Although most urologists have taken laparoscopy courses, this modality has not been widely incorporated into their practices at present.

Child↗

PubMed2000

Effect of preoperative biofeedback/pelvic floor training on continence in men undergoing radical prostatectomy.

OBJECTIVES: To determine whether preoperative biofeedback training improves urinary continence overall or the rate of return of continence in men undergoing radical prostatectomy. METHODS: One hundred men scheduled to undergo radical prostatectomy were randomized to receive graded pelvic muscle exercise training with biofeedback 2 to 4 weeks before surgery or to a control group performing pelvic muscle exercises without biofeedback. The biofeedback group was instructed to continue exercises four times per day until surgery and to resume exercises when the urethral catheter was removed following surgery. The control group received written and brief verbal instructions in pelvic muscle exercises before surgery and again after catheter removal. Urinary continence was assessed by personal or phone interviews. RESULTS: Six months following surgery, the continence rates, as defined by the use of one pad or less per day, were 94% (44 of 47) and 96% (48 of 50) in the biofeedback and control groups, respectively (P = 0.596). Also, the rate of return as determined at time points 1, 2, 3, and 4 months after surgery was not significantly different between the two groups. CONCLUSIONS: Preoperative biofeedback training did not improve the outcome of pelvic muscle exercises on overall continence or the rate of return of urinary control in men undergoing radical prostatectomy.

Biofeedback, Psychology↗