Biomedical subjects

K B Kim

Publications and source records attributed to K B Kim.

At least 19 recordsLinked to original sources

PubMed2003

Relation between insulin resistance and hematological parameters in elderly Koreans-Southwest Seoul (SWS) Study.

In this study, we investigated the relation between insulin resistance and hematological parameters in elderly Koreans. This study included 1314 non-diabetic subjects over the age of 60, selected from a cross-sectional study, which was conducted in 1999 in Seoul, Korea. We measured fasting and post-load 2 h plasma glucose, insulin levels, lipid profiles, anthropometric measures, and hematological parameters. The degree of insulin resistance was assessed using the homeostasis model assessment (HOMA). We found a correlation between insulin resistance and hemoglobin concentrations in non-smoking men (r=0.20, P=0.0186). In non-smoking women, insulin resistance correlated with hemoglobin (r=0.10, P=0.0017) and with white blood cell (WBC) count (r=0.15, P=0.001). Hemoglobin concentrations and WBC counts were also associated with other components of the insulin resistance syndrome such as body mass index, blood pressure, lipid profiles and fasting plasma insulin levels (surrogate for insulin resistance). Furthermore, the group in the upper quartile for insulin resistance showed higher hemoglobin concentrations and WBC counts than the lower quartile, independent of smoking status and serum iron concentrations. Using HOMA-IR as a dependent variable in a multiple regression analysis, age, body mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure, HDL cholesterol, triglyceride, WBC count, hemoglobin, hematocrit and serum TIBC were significant. Our results provide support for a relation between insulin resistance/hyperinsulinemia and hematological parameters such as hemoglobin concentrations and WBC counts in elderly Koreans. This suggests that increased erythropoiesis and subclinical inflammation could be part of the metabolic syndrome in elderly Koreans.

Aged↗

PubMed2003

Factor analysis of the metabolic syndrome among elderly Koreans--the South-west Seoul Study.

AIMS: To examine the relationship between the components of the metabolic syndrome and to explore whether insulin resistance unifies the clustering of components of the metabolic syndrome among urban elderly Koreans using exploratory factor analysis. METHODS: We included 1314 non-diabetic subjects over the age of 60 years, selected from a cross-sectional study, which was conducted in 1999 in Seoul, Korea. Factor analysis was carried out using the principle components analysis with Varimax orthogonal rotation of the components of the metabolic syndrome. RESULTS: We found four major factors of cardiovascular disease risk variables in our study subjects. Impaired glucose tolerance, dyslipidaemia, hypertension and obesity aggregated as the major domain. Obesity and dyslipidaemia variables were closely related and loaded on the same factor. However, hypertension was not linked closely with other factors of the metabolic syndrome. CONCLUSIONS: Insulin resistance is not the only contributor to the metabolic syndrome among urban elderly Koreans. Although the components of the metabolic syndrome were closely related, the finding of more than one factor suggests that more than one pathophysiological mechanism underlies full expression of the metabolic syndrome among elderly Koreans.

Aged↗

PubMed2003

Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro.

We have found that the ubiquitin-proteasome pathway exerts exquisite control of osteoblast differentiation and bone formation in vitro and in vivo in rodents. Structurally different inhibitors that bind to specific catalytic beta subunits of the 20S proteasome stimulated bone formation in bone organ cultures in concentrations as low as 10 nM. When administered systemically to mice, the proteasome inhibitors epoxomicin and proteasome inhibitor-1 increased bone volume and bone formation rates over 70% after only 5 days of treatment. Since the ubiquitin-proteasome pathway has been shown to modulate expression of the Drosophila homologue of the bone morphogenetic protein-2 and -4 (BMP-2 and BMP-4) genes, we examined the effects of noggin, an endogenous inhibitor of BMP-2 and BMP-4 on bone formation stimulated by these compounds and found that it was abrogated. These compounds increased BMP-2 but not BMP-4 or BMP-6 mRNA expression in osteoblastic cells, suggesting that BMP-2 was responsible for the observed bone formation that was inhibited by noggin. We show proteasome inhibitors regulate BMP-2 gene expression at least in part through inhibiting the proteolytic processing of Gli3 protein. Our results suggest that the ubiquitin-proteasome machinery regulates osteoblast differentiation and bone formation and that inhibition of specific components of this system may be useful therapeutically in common diseases of bone loss.

Animals↗

PubMed2001

Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation.

The intracellular levels of many proteins are regulated by ubiquitin-dependent proteolysis. One of the best-characterized enzymes that catalyzes the attachment of ubiquitin to proteins is a ubiquitin ligase complex, Skp1-Cullin-F box complex containing Hrt1 (SCF). We sought to artificially target a protein to the SCF complex for ubiquitination and degradation. To this end, we tested methionine aminopeptidase-2 (MetAP-2), which covalently binds the angiogenesis inhibitor ovalicin. A chimeric compound, protein-targeting chimeric molecule 1 (Protac-1), was synthesized to recruit MetAP-2 to SCF. One domain of Protac-1 contains the I kappa B alpha phosphopeptide that is recognized by the F-box protein beta-TRCP, whereas the other domain is composed of ovalicin. We show that MetAP-2 can be tethered to SCF(beta-TRCP), ubiquitinated, and degraded in a Protac-1-dependent manner. In the future, this approach may be useful for conditional inactivation of proteins, and for targeting disease-causing proteins for destruction.

Aminopeptidases↗

PubMed2001

FLASH coordinates NF-kappa B activity via TRAF2.

FLASH is a protein recently shown to interact with the death effector domain of caspase-8 and is likely to be a component of the death-inducing signaling complex in receptor-mediated apoptosis. Here we show that antisense oligonucleotide-induced inhibition of FLASH expression abolished TNF-alpha-induced activation of NF-kappaB in HEK293 cells, as determined by luciferase reporter gene expression driven by a NF-kappaB responsive promoter. Conversely, overexpression of FLASH dose-dependently activated NF-kappaB, an effect suppressed by dominant negative mutants of TRAF2, NIK, and IKKalpha, and partially by those of TRAF5 and TRAF6. TRAF2 was co-immunoprecipitated with FLASH from the cell extracts of HEK293 cells or HeLa cells stably expressing exogenous FLASH (HeLa/HA-FLASH). Furthermore, serial deletion mapping demonstrated that a domain spanning the residues 856-1191 of FLASH activated NF-kappaB as efficiently as the full-length and could directly bind to TRAF2 in vitro and in the transfected cells. Taken together, these results suggest that FLASH coordinates downstream NF-kappaB activity via a TRAF2-dependent pathway in the TNF-alpha signaling.

Animals↗

PubMed2001

The ubiquitin-proteasome pathway and proteasome inhibitors.

The ubiquitin-proteasome pathway has emerged as a central player in the regulation of several diverse cellular processes. Here, we describe the important components of this complex biochemical machinery as well as several important cellular substrates targeted by this pathway and examples of human diseases resulting from defects in various components of the ubiquitin-proteasome pathway. In addition, this review covers the chemistry of synthetic and natural proteasome inhibitors, emphasizing their mode of actions toward the 20S proteasome. Given the importance of proteasome-mediated protein degradation in various intracellular processes, inhibitors of this pathway will continue to serve as both molecular probes of major cellular networks as well as potential therapeutic agents for various human diseases.

Cysteine Endopeptidases↗

PubMed2001

Modifications of the Cox-Maze III procedure.

BACKGROUND: The extended operative time needed for surgery with complicated atrial incisions may preclude application of the Cox-Maze III procedure (CM-III) as a concomitant operation. And after the CM-III, left atrial (LA) contraction has been reported to recover in reduced magnitude compared with right atrial (RA) contraction. METHODS: To decrease operative time, we have modified the CM-III (modification I) by: obliterating the LA appendage instead of excising it; cryoablating the bridge between the LA appendage and margin of the pulmonary vein encircling incision; extending the lateral incision of RA onto the RA appendage without excising it, and extending the incision more inferiorly toward the inferior vena cava; and omitting the T-incision of RA. We compared the clinical results of the conventional CM-III (group 1, n = 18) with those of the modified CM-III group (group 2, n = 23) performed in patients with rheumatic mitral valve (MV) disease. To enlarge the contractile area of the LA, we modified the CM-III to encircle the right and left pulmonary veins separately (modification II), and compared the LA contractilities of the conventional CM-III (group A, n = 15) with those of the second modification (group B, n = 9). RESULTS: Modification I: Mean aortic cross-clamp (ACC) times (135 +/- 29 versus 104 +/- 18 minutes, p < 0.005) and cardiopulmonary bypass (CPB) times (240 +/- 33 versus 185 +/- 42 minutes, p < 0.001) were significantly decreased in group 2 compared with those in group 1. In group 1, sinus rhythm was restored in 16 patients (88.9%). RA contractility was demonstrated in 100% of patients with sinus rhythm (16 of 16) and LA contractility in 75% (12 of 16) in the latest follow-up echocardiography. In group 2, sinus rhythm was restored in 21 patients (91.3%). RA contractility was demonstrated in 100% of patients with sinus rhythm (21 of 22) and LA contractility in 76.2% (16 of 21). Modification II: Mean ACC times were increased in group B compared with group A (133 +/- 32 versus 172 +/- 39 minutes, p = 0.02). The A velocities at LA contraction and the ratio of atrial contraction to peak early diastolic filling velocity (A/E ratio) of the trans-mitral flow were 0.14 +/- 0.20 m/sec and 0.23 +/- 0.11 in group A, and 0.58 +/- 0.33 m/sec and 0.47 +/- 0.19 in group B, respectively, both showing a significant increase in group B compared with group A (p < 0.05). CONCLUSIONS: Our first modification of the CM-III showed comparable sinus conversion rates and incidence of atrial contractility restoration with significantly shorter ACC and CPB times than the conventional CM-III. The second modification of the CM-III significantly increased the LA contractility when compared with the conventional CM-III, although the second modification required a longer ACC time.

Adult↗

PubMed2001

Intraaortic balloon pump therapy facilitates posterior vessel off-pump coronary artery bypass grafting in high-risk patients.

BACKGROUND: Displacement of the heart to expose posterior vessels during coronary artery bypass grafting (CABG) without cardiopulmonary bypass (off-pump CABG, or OPCAB) may impair cardiac function. We used the intraaortic balloon pump (IABP) preoperatively to reduce operative risk and to facilitate posterior vessel OPCAB in high-risk patients with left main coronary artery disease (> 75% stenosis), intractable resting angina, postinfarction angina, left ventricular dysfunction (ejection fraction < 35%), or unstable angina. METHODS: One hundred and forty-two consecutive patients who underwent multivessel OPCAB including posterior vessel revascularization were studied prospectively. The patients were divided into group I (n = 57), which received preoperative or intraoperative IABP, and group II (n = 85), which did not receive IABP. In group I, there were 34 patients with left main coronary artery disease, 24 patients with intractable resting angina, 8 patients with left ventricular dysfunction, 5 patients with postinfarction angina, and 40 patients with unstable angina. Seven patients received intraoperative IABP support owing to hemodynamic instability during OPCAB. RESULTS: There was no operative mortality in group I and 1 death in group II. The average number of distal anastomoses was not different between group I and group II (3.4 +/- 0.9 versus 3.5 +/- 0.9, p = not significant). There were no significant differences in the number of posterior vessel anastomoses per patient. There were no differences in ventilator support time, length of stay in the intensive care unit, hospital stay, and morbidity between the two groups. There was one IABP-related complication in group I. CONCLUSIONS: IABP therapy facilitates posterior vessel OPCAB in high-risk patients, and surgical results are comparable with those in lower-risk patients.

Aged↗

PubMed2001

Off-pump coronary artery bypass may decrease the patency of saphenous vein grafts.

BACKGROUND: There is concern that a hypercoagulable status is caused after coronary artery bypass grafting without cardiopulmonary bypass (off-pump coronary artery bypass grafting, or OPCAB) and may potentially endanger the patency of the anastomosis. The aims of this study were: (1) to compare 1-year graft patency after OPCAB with that of conventional coronary artery bypass grafting (CABG) and that of on-pump beating CABG; and (2) to demonstrate any differences in patency of various conduits among the three groups. METHODS: We analyzed the results of 122 consecutive OPCAB cases (group 1) compared with those of 65 consecutive conventional CABG cases (group II) and those of 19 consecutive on-pump beating CABG cases (group III). In group I, coronary angiography (CAG) was performed immediately postoperatively and 1 year after surgery. In groups II and III, CAG was performed 1 year after surgery. Graft patency was graded as grade A (excellent), grade B (fair), or grade O (occluded). RESULTS: The average number of distal anastomoses in groups I, II, and III were 3.1 +/- 1.1, 3.7 +/- 0.9, and 3.6 +/- 0.9, respectively. In group I, postoperative CAG was performed in 92% of patients (112/122) before discharge. The patency rate (grade A + B) was 96.4% (162/168) for arterial grafts, and 85.6% (160/187) for saphenous vein grafts (SVG). One-year follow-up CAG was performed in 74% of patients (90/122). The patency rate was 97.8% (132/135) for arterial grafts and 67.9% (106/156) for SVG. In group II, 1-year follow-up CAG was performed in 65% of patients (42/65). The patency rate (grade A + B) was 93.5% (43/46) for arterial grafts and 88.3% (98/111) for SVG. In group III, 1-year follow-up CAG was performed in 89% of patients (17/19). The patency rate (grade A + B) was 100% (19/19) for arterial grafts and 86.8% (33/38) for SVG. CONCLUSIONS: Our results demonstrate that the patency rate ot SVG after OPCAB was significantly lower than that of arterial grafts in the early postoperative CAG (p < 0.001), and was also significantly lower than those of SVG of group II (p < 0.001) and group III (p < 0.01) in the postoperative 1-year CAG, although there was no significant difference in 1-year patency of arterial grafts among the three groups. Our data suggest that a specific perioperative anticoagulant therapy may be advisable in patients undergoing OPCAB with SVG.

Anastomosis, Surgical↗

PubMed2001

Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress.

AIMS: it appears that hypertriglyceridemia (HTG) is a risk factor of atherosclerosis as demonstrated by recent studies. In this study, we analyzed the effects of acute HTG on endothelial function and oxidative stress, which are important mechanisms in the pathogenesis of atherosclerosis. METHODS AND RESULTS: in a high fat meal group (n = 11), serum triglycerides and PMA-activated leukocyte O(2)(-)* production were significantly (P < 0.005) increased from 146 +/- 69 mg/dl and 4.09 +/- 0.93 nmol/10(6) cells/min preprandially to 198 +/- 88 mg/dl and 5.49 +/- 1.19 nmol/10(6) cells/min, respectively, 2 h after eating a high-fat meal. The flow-mediated endothelium-dependent brachial artery dilation (FMD; high-resolution ultrasound) was decreased from 13.7 +/- 3.3% preprandially to 8.2 +/- 3.7%, 2 h after eating a high-fat meal (P < 0.005). However, following a low-fat meal (n = 9), there were no significant changes in triglycerides, leukocyte O(2)(-)* production and FMD. Changes of serum triglycerides were correlated negatively (r = -0.650, P < 0.005) with changes of FMD, but were correlated positively (r = 0.798, P < 0.001) with changes of leukocyte O(2)(-)* production, which - in turn - were correlated negatively (r = -0.784, P < 0.001) with changes of FMD in all study subjects (mean age: 56 years, n = 20). CONCLUSIONS: this study suggests that acute HTG causes endothelial dysfunction via enhanced oxidant stress and this may pave the way for the development of atherosclerosis under chronic conditions.

Acute Disease↗

PubMed2001

Lack of proteasome active site allostery as revealed by subunit-specific inhibitors.

The chymotrypsin-like (CT-L) activity of the proteasome is downregulated by substrates of the peptidyl-glutamyl peptide hydrolyzing (PGPH) activity. To investigate the nature of such interactions, we synthesized selective alpha',beta'-epoxyketone inhibitors of the PGPH activity. In cellular proliferation and protein degradation assays, these inhibitors revealed that selective PGPH inhibition was insufficient to inhibit protein degradation, indicating that the CT-L and PGPH sites function independently. We also demonstrated that CT-L inhibition by a PGPH substrate does not require the occupancy of the PGPH site or hydrolysis of the PGPH substrate. Thus, these results support a model in which a substrate of one subunit regulates the activity of another via binding to a noncatalytic site(s) rather than through binding to an active site.

Allosteric Regulation↗

PubMed2001

Expression of thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection.

We evaluated the expression of thymidylate synthase (TS) in locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection and investigated the association between TS expression and clinicopathologic characteristics including prognosis of the patients. TS expression was evaluated by immunohistochemical staining using TS106 monoclonal antibody in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil (5-FU) and doxorubicin-based adjuvant chemotherapy after curative resection. 65 patients (63%) had primary tumours with high TS expression (> or = 25% of tumour cells positive), and 38 patients (37%) demonstrated low TS expression (< 25% of tumour cells positive or no staining). High TS expression was associated with male gender (P = 0.002), poorly differentiated histology (P = 0.015), and mixed type in Lauren's classification (P = 0.027). There were no statistically significant differences in 4-year disease-free survival (60.0% vs. 57.2%, P = 0.548) and overall survival (59.6% vs. 59.3%, P = 0.792) between high-TS group and low-TS group. In conclusion, although high TS expression was associated with poorly differentiated histology and mixed type in Lauren's classification, it did not predict poor disease-free and overall survival in gastric cancer patients treated with 5-FU and doxorubicin-based adjuvant chemotherapy after curative resection. Further prospective studies including the evaluation of other biological markers associated with the resistance to 5-FU and doxorubicin are necessary.

Adult↗

PubMed2001

General pharmacological properties of YJA20379-8, a new H+/K(+)-ATPase inhibitor with anti-ulcer activities.

The general pharmacological properties of YJA20379-8 (3-butyryl-4-[(R)-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, CAS 187654-40-6), a new H+/K(+)-ATPase inhibitor with anti-ulcer activities, were investigated in mice, rats and guinea pigs. YJA20379-8 at oral doses of 25, 50 and 100 mg/kg did not affect the locomotor activity, hexobarbital hypnosis and motor coordination in mice. The drug did not have analgesic action and anticonvulsant action at the doses of 100 mg/kg p.o. The respiration and blood pressure were not affected at 10 mg/kg i.v. in rats. YJA20379-8 at 2 x 10(-4) g/ml did neither produce any contraction nor relaxation of isolated organs, such as guinea pig ileum, rat fundus, rat uterus and guinea pig vas deferens, and the drug antagonized the contractile responses to several spasmogens, such as acetylcholine, histamine, serotonin, L-phenylephrine, oxytocin and BaCl2. The drug up to 100 mg/kg p.o. did not affect pupil size and the intestinal propulsion of mice. And it did not show an anticarrageenan action at 100 mg/kg. In this general pharmacology study, hypothermic effect in mice, retardation in gastric emptying in rats, decreases in urine excretion in rats at oral doses of 50 and 100 mg/kg of YJA20379-8 and the spasmolytic activity could be found. However, no other effects were exhibited at a high oral dose of 100 mg/kg in animals in this study.

Animals↗

PubMed2001

Intracranial cerebral artery disease as a risk factor for central nervous system complications of coronary artery bypass graft surgery.

BACKGROUND AND PURPOSE: Although extracranial carotid artery disease (ECAD) is accepted as a risk factor for central nervous system (CNS) complications after coronary artery bypass graft (CABG) surgery, it remains to be clarified whether intracranial cerebral artery disease (ICAD) may also increase the risk. We conducted a prospective study to elucidate the relation between ICAD and CNS complications after CABG surgery. METHODS: We prospectively studied 201 patients undergoing nonemergency isolated CABG surgery during a 39-month period (from March 1995 to June 1998). Each patient was evaluated before surgery with neurological examination, transcranial Doppler, and carotid duplex ultrasonography. Magnetic resonance angiography was used to determine the presence and severity of ECAD and ICAD in patients with abnormal findings on clinical examination, carotid duplex ultrasonography, or transcranial Doppler. Patients were followed after surgery and evaluated for the development of CNS complications. Association between CNS complications and their potential predictors was analyzed. RESULTS: One hundred nine patients (54.2%) were found to have ECAD and/or ICAD. ECAD alone was found in 48 patients (23.9%), ICAD alone in 33 (16.4%), and both ECAD and ICAD in 28 (13.9%). Fifty-one patients (25.4%) had single or multiple CNS complications: 23 (11.4%) had delirium; 18 (9.0%) had hypoxic-metabolic encephalopathy; 7 (3.5%) had stroke; and 7 (3. 5%) had seizure. In multivariate analysis, ICAD was found to have an independent association with the development of CNS complications (prevalence OR, 2.28; 95% CI, 1.04 to 5.01) after controlling for covariates including age, occurrence of intraoperative events, and reoperation. The joint effect of ECAD and ICAD was also statistically significant and stronger than ICAD alone (prevalence OR, 3.87; 95% CI, 1.80 to 6.52). CONCLUSIONS: Our results suggest that ICAD may be an independent risk factor for CNS complications after CABG surgery. These results support pre-CABG evaluation of the intracranial arteries for the risk assessment of CABG surgery, at least in black and Asian patients, in whom there may be a higher prevalence of intracranial arterial stenosis.

Adult↗

PubMed2001

Cardiovascular disease risk factors in Korean American elderly.

An in-depth cardiovascular risk factor assessment was carried out in a sample of 205 Korean American elderly in Maryland, consisting of 75 males and 130 females aged 60 to 89 years (mean age = 69.9 +/- 6.5 years). Six risk factors were assessed in each participant: high blood pressure, current smoking, high blood cholesterol, overweight, sedentary lifestyle, and diabetes. The findings of this cross-sectional study suggested that high blood pressure was the leading cardiovascular disease risk factor among Korean American elderly (71%), followed by high blood cholesterol (53%), overweight (43%), sedentary life style (24%), diabetes (18%), and smoking (7%). Two thirds of the sample had multiple cardiovascular disease risk factors. The pattern of prevalence and risk factors that was observed was consistent with the distribution of multiple risk factors in that the combination of high blood pressure, high blood cholesterol, and overweight was most common in Korean American elderly (62%). These findings indicate that culturally relevant and salient strategies are needed to reduce multiple risk factors in this population.

Aged↗

PubMed2001

Recent advances in the management of squamous cell carcinoma of the head and neck.

Therapeutic outcomes of the currently used chemotherapeutic agents for recurrent or advanced head and neck squamous cell carcinoma, such as methotrexate or a combination of 5-fluorouracil and cisplatin, are far beyond satisfaction. New chemotherapeutic agents, such as taxanes, paclitaxel and docetaxel, are among the most active drugs for head and neck cancer and a number of multidrug regimens containing a taxane and cisplatin have produced equivalent or higher response rates than conventional regimens. In addition, early clinical trials of novel molecular-targeted agents, such as epidermal growth factor receptors, tyrosine kinase inhibitors and gene targeted therapy, have shown encouraging results. Further clinical trials will be needed to optimally combine the biologic agents with chemotherapy and assess their effects on long-term control of cancer.

Carcinoma, Squamous Cell↗

PubMed2001

Transplacental transfer and age-related levels of serum IgG antibodies to the capsular polysaccharides of Streptococcus pneumoniae types 14 and 19 in Korea.

Little is known about the prevalence of naturally acquired IgG antibodies to the capsular polysaccharides of Streptococcus pneumoniae (pneumococcal IgG) in Korea. In the present study, we investigated transplacental transfer and age-related levels of pneumococcal IgG to provide background seroepidemiologic data for S. pneumoniae in Korea. One hundred thirty eight sera were assayed by ELISA for IgG to pneumococcal polysaccharide capsular serotypes 14 and 19, the predominant serotypes for under 15 yr of age in Korea. The subjects were divided into 7 subgroups according to age. The cord/maternal geometric mean titer of pneumococcal were 4.47+/-5.88/5.21 +/- 5.88 for serotype 14, and 4.68 +/- 5.55/6.55 +/- 6.92 for serotype 1 9 (mean +/- standard deviation, microg/mL). After birth, the geometric mean titers of pneumococcal IgG for serotypes 14 and 19 expressed in microg/mL were 1.18+/-2.12 and 1.41+/-2.17 in the 0-6 months group, 0.27+/-0.19 and 0.69+/-0.93 in 7-12 months, 0.21+/-0.22 and 0.64+/-1.32 in 1-2 yr, 0.69+/-0.78 and 2.65+/-2.46 in 3-6 yr, 2.52+/-2.72 and 8.29+/-4.24 in 7-10 yr, respectively. In conclusion, reduced transplacental transfer and very low serum concentrations of pneumococcal IgG may contribute to the susceptibility of neonates, infants, and young children to S. pneumoniae infection.

Age Factors↗

PubMed2001

Histological and neurotrophic changes triggered by varying models of bladder inflammation.

PURPOSE: We determined whether bladder inflammation causes elevated expression of nerve growth factor by bladder parenchymal cells, leading to alterations in neurons innervating the bladder. To answer this question biochemical, histological and neuronal size data were obtained in rats following various experimental models of bladder inflammation. MATERIALS AND METHODS: Chemical (2.5% formalin), immune (lipopolysaccharide 2 x 104 cfu/ml.) and mechanical (chromic catgut) inflammation was evaluated at various times and compared to control bladders. Hematoxylin and eosin, and Giemsa staining was done to characterize inflammation and quantify mast cells in the bladder. Nerve growth factor protein and messenger RNA were assayed in the bladder and major pelvic ganglion using 2-site enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction, respectively. Retrograde axonal tracing was done to size bladder neurons in the major pelvic and dorsal root ganglia. RESULTS: All forms of inflammation increased bladder weight and produced diffuse hyperplasia, intramural edema, acute and chronic inflammatory cells, infiltration and mastocytosis. Generally bladder inflammation resulted in a 50% increase in nerve growth factor and 52% to 58% enlargement of peripheral neurons. CONCLUSIONS: Inflammation results in altered nerve growth factor content of the bladder, and morphological changes in sensory and motor neurons innervating the bladder. Such neuroplasticity may be a possible explanation for the association of bladder inflammation with long-term symptoms and pain after inflammation subsides.

Animals↗