Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 847 records · Page 47Linked to original sources

PubMed1996

Bacterial translocation in a large-animal model of small-bowel transplantation. Portal vs systemic venous drainage and the effect of tacrolimus immunosuppression.

OBJECTIVE: To study whether bacterial translocation is more prevalent after small-bowel transplantation with systemic venous drainage (SVD) vs portal venous drainage (PVD) and whether it is influenced by immunosuppression. DESIGN: We performed 15 small-bowel transplantations in pigs. Group 1 (n = 5) had SVD and no immunosuppression; group 2 (n = 6), PVD and no immunosuppression; and group 3 (n = 4), PVD and immunosuppression with tacrolimus and methylprednisolone sodium succinate. Portal and systemic blood, portal and mesenteric lymph nodes, and liver were cultured in donors and recipients on postoperative day 0 (POD 0) and in recipients on postoperative day 3 (POD 3). Jejunal and ileal contents were also sampled at these times. SUBJECTS: Outbred male Yorkshire-Landrace pigs. MAIN OUTCOME MEASURES: (1) Blood and tissue bacterial cultures, (2) blood endotoxin levels, and (3) histopathologic examination. RESULTS: Cultures were positive for bacteria in 32% (16/50) of samples on POD 0 and 88% (22/25) on POD 3 in group 1, in 18% (11/60) of samples on POD 0 and 97% (29/30) on POD 3 in group 2, and in 8% (3/40) of samples on POD 0 and 95% (19/20) on POD 3 in group 3. Systemic blood cultures were positive for bacteria on POD 3 in 60% (3/5) of pigs in group 1, 83% (5/6) in group 2, and 100% (4/4) in group 3. Significantly more bacteria were present in the ileum than in the jejunum on POD 0 in group 2; this difference approached significance in groups 1 and 3. Bacterial numbers were identical in the ileum and jejunum by POD 3 in all groups. Circulating endotoxin levels were significantly elevated on POD 3 vs POD 0 only in group 1. Endotoxin levels were not significantly different between the SVD group (group 1) and either PVD group (groups 2 and 3). CONCLUSIONS: Bacterial translocation is prevalent after small-bowel transplantation in pigs whether PVD or SVD is used. Immunosuppression with tacrolimus does not prevent bacterial translocation but may reduce systemic endotoxemia.

Animals↗

PubMed1996

Cloning and characterization of the murine homolog of the sno proto-oncogene reveals a novel splice variant.

The cellular function(s) of the SNO protein remain undefined. To gain a better understanding of possible developmental roles of this cellular proto-oncogene, we have cloned two murine sno cDNAs and have investigated their expression patterns in embryonic and postnatal tissues. A single major transcript of 7.5 kb is detected in multiple tissues by Northern blot. However, reverse transcriptase polymerase chain reaction (RT-PCR) and RNAse protection assays revealed a novel splice variant in every tissue examined. Two isoforms, termed sno N and sno-dE3 (dE3, deletion within exon 3), were identified. The sno-dE3 isoform employs a novel 5' splice site located within the coding region of the third exon and deletes potential kinase recognition motifs. Transcripts of both sno isoforms accumulate ubiquitously but are most abundant in the developing central nervous system. The in situ hybridization patterns of sno expression during murine development suggest potential roles in tissues with a high degree of cellular proliferation. Expression in terminally differentiated tissues such as muscle and neurons indicates that SNO may have multiple functional activities.

Alternative Splicing↗

PubMed1996

Optimization of environmental factors for the production and handling of recombinant retrovirus.

Certain steps from the production to infection of the amphotropic retroviral vector, MFG- LacZ, were optimized and the factors that affect retroviral titers were analyzed. Retroviral vector titers were highest when the culture supernatant was harvested 3 days after the producer cells had reached confluence. About a 2-fold increase in vector production was achieved at 32 degrees C compared to that at 37 degrees C. Low serum concentrations had no significant effect on the titers of virus produced by the CRIP cell line. Retroviral vectors were stable at 4 degrees C but very unstable at 37 degrees C and were quite sensitive to freezing and thawing. About 30%-50% of viral infectivity was lost during the thawing step and the loss was not recovered by the addition of commonly used cryoprotectants. Increase in viral exposure time for infection to target NIH3T3 cells was linearly proportional to the retroviral titer for up to 15 h. In addition, using DEAE-dextran in place of polybrene as a polycation during infection enhanced infection efficiency about 3-fold. The retrovirus was robust to simple ultrafiltration and its titer could be easily concentrated 16-fold. Taken together, our data suggest that at least a 100-fold increase in titer can be achieved with simple optimization.

3T3 Cells↗

PubMed1996

The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage.

The coagulation cascade has a potential role in brain edema formation due to intracerebral hemorrhage. In this study blood and other solutions were injected stereotactically into the right basal ganglia in rats. Twenty-four hours following injection, brain water and ion contents were measured to determine the amount of brain edema. Intracerebral blood resulted in an increase in brain water content. The amount of brain edema surrounding the intracerebral hematoma was reduced by a thrombin inhibitor N alpha-(2-Naphthalenesulfonylglycyl)-4-amidino-DL-phenylalaninep iperidide, (alpha-NAPAP) infused into the hematoma after the clot had been allowed to solidify. The inhibitor did not alter the actual size of the clot mass. An artificial clot composed of fibrinogen, thrombin, and styrene microspheres also produced brain edema. A fibrin clot led to edema formation even in the absence of mass effect provided by the microspheres. The single component responsible for production of brain edema in all these models was thrombin. The edema was formed in response to a fibrinogen-independent pathway. These results indicate that the coagulation cascade is involved in brain edema that develops adjacent to an intracerebral hematoma.

Animals↗

PubMed1996

Assessing neuroreceptor occupancy by continuous infusion of carbon-11 labeled radioligands.

In carbon-11 labeled radiotracer studies of neuroreceptors in the brain, a state of practical equilibrium, monitored with a simple dual-probe detector system, was achieved by injection of a bolus of tracer followed by a continuous infusion of the tracer. After investigating several different bolus-to-infusion activity ratios, we observed that a practical equilibrium state could be achieved with a slope of 0.02+/-0.001 cpsxkg/microCi/min for [11C]carfentanil studies in normal human beings. The usefulness of this approach to assess neuroreceptor occupancy was demonstrated in two cases.

Adult↗

PubMed1996

Is lidocaine-prilocaine cream (EMLA) always useful for venous puncture in preoperative autologous blood donation?

PURPOSE: The goal of the present study was to evaluate in adults the benefit of the Eutectic Mixture of Local Anesthetics (EMLA) for preoperative autologous blood donation. METHODS: Twenty-six adult patients requiring three blood samples were studied. The pain of venipuncture was assessed by the patient using a 100 mm Visual Analogue Scale (VAS) and a four-category Verbal Rating Scale (VRS). The first puncture was performed without anaesthesia, as a "reference puncture". The second and third punctures were performed with EMLA and placebo in a double-blind cross-over randomization. For statistical analysis, the patients were allocated to two groups according to the VAS scores of the reference puncture: (Group 1) VASref < 20 mm; (Group 2) VASref > or = 20 mm. RESULTS: For the whole 26 patients, the VAS and the VRS pain scores were lower for EMLA puncture than for both the placebo and reference punctures (P < 0.05). Twenty patients had a VASref < 20 mm and six patients a VASref > or = 20 mm. In Group 1, there was no difference between EMLA and placebo for both the VAS and VRS scores. In contrast, in Group 2, the VAS score was lower for EMLA than for both the placebo and the reference punctures (respectively 11 +/- 7.1, 28.9 +/- 7.9, 29.1 +/- 6.4; P < 0.01); the VRS score was also lower for EMLA puncture than for placebo puncture (P < 0.05). CONCLUSION: In adults requiring repeated venous punctures, pain from cannulation may be evaluated at the first puncture with a Visual Analogue Scale, thus indicating or not the need for EMLA.

Adult↗

PubMed1996

The work of auxiliary nurses in Mexico: stressors, satisfiers and coping strategies.

Recruitment and retention of nursing personnel is a major problem in many parts of the world, particularly developing countries. Strategies for promoting job satisfaction can help reduce the costs of high turnover and increase the quality of patient care. As part of a larger international study on women's health, a convenience sample of 59 Mexican nursing assistants and technical nurses, categorized as auxiliary nurses, were asked to complete a questionnaire designed to elicit their perceived work-related stresses and satisfactions, as well as the coping strategies they utilized to diminish work-associated stress. Major satisfiers included self-fulfillment, providing service and working as a member of a team. Frequent stressors were interpersonal relations, "angustia" (anguish), work overload and the work environment. These auxiliary nursing personnel utilized problem-solving techniques, recreational activities, talking to family and friends and actively trying to relax themselves in order to cope with their work-related stress.

Adaptation, Psychological↗

PubMed1996

Selection of peptides that bind to the HLA-A2.1 molecule by molecular modelling.

Cytotoxic T lymphocytes recognize antigenic peptides in association with major histocompatibility complex class I proteins. Although a large set of class I binding peptides has been described, it is not yet easy to search for potentially antigenic peptides without synthesis of a panel of peptides, and subsequent binding assays. In order to predict HLA-A2.1-restricted antigenic epitopes, a computer model of the HLA-A2.1 molecule was established using X-ray crystallography data. In this model nonameric peptide sequences were aligned. In a molecular dynamics (MD) simulation with two sets of peptides known to be presented by HLA-A2.1, it was important to know the anchor amino acid residue preference and the distance between the anchor residues. We show here that the peptides bound to the HLA-A2.1 model structure possess a side chain of C-terminal anchor residue oriented into the binding groove with different distances between the two anchor residues from 15 to 21A. We also synthesized a set of nonamer peptides containing amino acid sequences of Hepatitis B virus protein that were selected on the basis of previously described HLA-A2.1 specific motifs. When results obtained from the MD simulation were compared with functional binding assays using the TAP-deficient cell line T2, it was evident that the MD simulation method improves prediction of the HLA-A2.1 binding epitope sequence. These results suggest that this approach can provide a way to predict peptide epitopes and search for antigenic regions in sequences in a variety of antigens without screening a large number of synthetic peptides.

Amino Acid Sequence↗

PubMed1996

Synthesis of heterocycles containing two cytosine or two guanine base-pairing sites. Novel tectons for self-assembly.

The synthesis of 1 and 2 is described, as is the X-ray structure of 1. Tecton 1 contains two DAA hydrogen bonding sites (cytosine-like), while 2 contains two DDA sites (guanosine-like). Tectons 1 and 2 were designed to self-assemble into a helical superstructure. Self-recognition of 1 occurs in the solid state with a novel inclusion of dimethylacetamide solvent.

Crystallography, X-Ray↗

PubMed1996

Relationship between severity of mitral regurgitation and prognosis of mitral valve prolapse: echocardiographic follow-up study.

We investigated the relation between the severity of mitral regurgitation and the development of complications and cardiac events by using two-dimensional and color Doppler echocardiography in 229 consecutive patients with mitral valve prolapse. The frequency of moderate and severe mitral regurgitation was significantly higher in patients with a prolapsed posterior leaflet (61%) than in patients with a prolapsed anterior leaflet (25%), and the older the patient, the greater the severity of mitral regurgitation. The occurrence of complications, such as atrial fibrillation, congestive heart failure, and chordal rupture, was significantly greater in prolapsed posterior leaflet cases than in prolapsed anterior leaflet cases, and the occurrence was closely associated with the degree of severity of mitral regurgitation. Multiple logistic regression analysis showed that the severity of mitral regurgitation is a strong prognostic indicator for developing complications. Furthermore in a subgroup of 49 patients tracked for a mean of 4.8 years, the new development of complications was significantly higher in patients who showed a progression in the severity of mitral regurgitation (52%) that in patients without progression in severity (8%). The initial severity of mitral regurgitation was related to the occurrence of cardiac events (mitral valve replacement, infective endocarditis, cerebral embolism and death). The data indicated that the progression of mitral regurgitation is closely associated with the development of complications and cardiac events and suggest that the severity of mitral regurgitation is an important prognostic indicator for the development of complications and cardiac events in patients with mitral valve prolapse.

Adolescent↗

PubMed1996

Weighted-ensemble Brownian dynamics simulations for protein association reactions.

A new method, weighted-ensemble Brownian dynamics, is proposed for the simulation of protein-association reactions and other events whose frequencies of outcomes are constricted by free energy barriers. The method features a weighted ensemble of trajectories in configuration space with energy levels dictating the proper correspondence between "particles" and probability. Instead of waiting a very long time for an unlikely event to occur, the probability packets are split, and small packets of probability are allowed to diffuse almost immediately into regions of configuration space that are less likely to be sampled. The method has been applied to the Northrup and Erickson (1992) model of docking-type diffusion-limited reactions and yields reaction rate constants in agreement with those obtained by direct Brownian simulation, but at a fraction of the CPU time (10(-4) to 10(-3), depending on the model). Because the method is essentially a variant of standard Brownian dynamics algorithms, it is anticipated that weighted-ensemble Brownian dynamics, in conjunction with biophysical force models, can be applied to a large class of association reactions of interest to the biophysics community.

Algorithms↗

PubMed1996

Improved analogs and novel delivery systems for somatostatin octapeptides.

Appropriate N-terminus modification can result in somatostatin (SRIF) octapeptide analogs that are both more potent and more selective in vitro for the human SRIF receptor type 2 (hsst2). In addition, these modifications can improve the duration of action and bioavailability of SRIF analogs following parenteral administration, as shown by both pharmacological and distribution studies in vivo with BIM-23190 and BIM-23197 in the rat.

Amino Acid Sequence↗

PubMed1996

Evaluation of urine acidification by urine anion gap and urine osmolal gap in chronic metabolic acidosis.

To investigate the clinical significance of urine anion gap and urine osmolal gap as indirect markers of urine acidification in chronic metabolic acidosis, we evaluated urine ammonium (NH4+), net acid excretion (NAE), urine anion gap (Na(+) + K(+) - Cl-), and urine osmolal gap (urine osmolality - [2(Na(+) + K(+)) + urea]) in 24 patients with chronic renal failure (CRF), eight patients with classic distal renal tubular acidosis (dRTA), and eight NH4Cl-loaded normal controls (NCs). Urine NH4+ excretion was lower (P < 0.001) in the CRF (5.4 +/- 0.6 mmol/d) and dRTA (19.2 +/- 2.7 mmol/d) patients than in the NCs (52.6 +/- 3.7 mmol/d); NAE was also lower (P < 0.001) in the CRF (9.8 +/- 1.6 mmol/d) and dRTA (16.7 +/- 4.7 mmol/d) patients than in the NCs (79.4 +/- 4.7 mmol/d). Urine anion gap was higher (P < 0.001) in the CRF (24.7 +/- 2.2 mmol/L) and dRTA (36.7 +/- 7.7 mmol/L) patients than in the NCs (-16.2 +/- 5.5 mmol/L). Urine osmolal gap was lower (P < 0.05) in the dRTA patients (129.7 +/- 17.0 mmol/L) than in the NCs (319.7 +/- 58.4 mmol/L). When the data from all subjects were pooled, urine anion gap correlated inversely with urine NH4+ (r = -0.70, P < 0.001) and with NAE (r = -0.83, P < 0.001), and urine osmolal gap correlated positively with urine NH4+ (r = 0.69, P < 0.01) and with NAE (r = 0.71, P < 0.05). We conclude that impaired urine acidification in CRF and dRTA patients is associated with an increase in urine anion gap and a decrease in urine osmolal gap, and that both urine anion gap and urine osmolal gap correlate well with NAE as well as with urine NH4+.

Acid-Base Equilibrium↗

PubMed1996

Endometrial effects of RU486 in primates--antiproliferative action despite signs of estrogen action and increased cyclin-B expression.

Continuous antiprogestin administration to hormone replaced, castrate monkeys inhibits estrogen-induced endometrial proliferation through mechanisms which remains unclear. To elucidate the molecular mechanisms of RU486-induced endometrial suppression, we treated six intact female cynomolgus monkeys on cycle days 2-22 sequentially with placebo, RU486 (1 mg/kg/day) and levonorgestrel (LNG) (2 microg/kg/day) intramuscularly (i.m.), with uterine wedge sections and endometrial biopsies collected on day 22 of each cycle. The uterine sections were evaluated for morphology, mitosis and proliferating cell nuclear antigen (PCNA) immunohistochemistry. Changes in the mRNA levels of ER, PR, cyclin-B and tumour suppressor gene p21 were assessed using co-amplification with beta-actin by reverse transcriptase-polymerase chain reaction (RT-PCR). Administration of RU486 uniformly resulted in characteristic suppression of endometrium with few mitosis, dense stroma and simple glands, whereas the effects of LNG were less uniform. Following RU486 administration, the levels of endometrial ER and PR mRNA were comparable to proliferative phase endometrium, and significantly higher than those seen in the secretory endometrium, indicating that some of the biological actions of E2 were not inhibited during RU486 treatment. Despite scarce mitosis, PCNA was readily detectable in all samples. Curiously, in comparison to secretory phase controls, the levels of cyclin-B, but not p21, mRNA were markedly increased following RU486. The effects of LNG on the levels of these mRNA species varied, with mean levels falling between those of the secretory phase controls, and RU486-treated specimens. The increase in cyclin-B mRNA and lack of mitosis suggests that anti-proliferative actions of RU486 in the primate endometrium might be associated with a cell-cycle block at the G2-M interphase. Whether mechanisms similar to these are associated with the beneficial clinical effects of RU486 seen in the treatment of various hormone dependent maladies remains to be determined.

Animals↗

PubMed1996

High resolution localization of endothelin receptors in rat renal medulla.

The cellular localization of endothelin receptors in the inner medulla of the rat kidney was investigated by using high resolution light and electron microscopic autoradiography, with the microwave irradiation fixation methods. Kidney slices were incubated with 125I-endothelin-1 alone or with selective ligands for the endothelin ETB and/or ETA receptors for light microscopic autoradiography. At the microscopic level, 125I-endothelin-1 was found to bind specifically to the glomeruli, arterioles and peritubular spaces in the cortex and vasa recta and surrounding tissues in the inner medulla. These bindings were also observed when the tissue slices were incubated in the presence of IRL1620 (ETB receptor agonist) or 97-139 (ETA receptor antagonist). Electron microscopic autoradiography using 125I-endothelin-1 in the inner medulla revealed silver grains over endothelial cells of the vasa recta and interstitial and collecting duct cells. No grains were detected over inner lining cells of the thin limbs of Henle's loop. These interstitial cells contained abundant microorganelles and lipid droplets, and had extensive cytoplasmic processes that closely related to the basement membranes of the vasa recta and loop of Henle. These findings demonstrate that type 1 interstitial cells are also primary sites for endothelin receptors as well as endothelial cells of the vasa recta and collecting duct cells in the inner medulla.

Animals↗

PubMed1996

Site-directed serology of HIV-1 subtype B infection: relation between virus specific antibody levels and disease progression.

Activated T helper (Th) cell-dependent (TD) antibody responses were determined over an 8-10 year period in 28 patients infected with HIV-1 subtype B. Twelve patients remain asymptomatic with normal CD4+ cell counts for 101-114 months. These individuals were defined as long-term asymptomatic (LTA). Sixteen patients progressed to severe immunodeficiency within 58-120 months. In samples derived close to the diagnosis of HIV-1, CD4+ cell counts were higher among the LTAs (P < 0.01). Antibody production driven by activated Th cells was determined using peptides corresponding to HIV-1 V3US/Eur, gp41, and the hepatitis C virus (HCV) core proteins. The less Th cell-dependent B cell antibody response was represented by measles virus immunity. Close to HIV-1 diagnosis, variable third (V3), gp41, HCV core, and measles antibody titres were at similar levels among the LTAs and the progressors. With time the LTAs displayed unchanged levels of V3 and gp41 antibodies, and slightly decreasing levels of HCV core antibodies (P < 0.05). In contrast, the progressors showed a decrease in all these antibody responses (P < 0.05, for all). In both groups, the levels of measles antibody remained stable. Our data show that no significant change of the antibody responses of LTAs is seen, even after 101-114 months of known HIV-1 infection. Furthermore, the marked decrease of TD antibody production in the progressors suggests that activated Th cells may be excellent targets for HIV-1 infection.

Adult↗

PubMed1996

Suppression of TRH-stimulated TSH secretion by glucose-induced hypothalamic somatostatin release.

To determine whether the combined glucose-thyrotropin-releasing hormone (TRH) test can be a useful method for the evaluation of the hypothalamic somatostatinergic activity, we investigated whether TRH-induced thyroid stimulating hormone (TSH) secretion can be suppressed by the oral glucose administration that stimulates the hypothalamic somatostatin (SRIH) secretion. Six tests were performed in ten healthy young men. Test 1: 1 ml of normal saline was intravenously administered at 0 min. Test 2: TRH was administered intravenously at 0 min. Test 3: Glucose, 75 g, was administered orally at -60 min. Test 4: Glucose and TRH were administered as above. Test 5: Pyridostigmine (PST), 120 mg, was given orally at -90 min followed by the administration of GH and TRH as above. Basal TSH levels were suppressed slightly, but significantly. In Test 3 compared to those observed in Test 1. The oral glucose administration also significantly suppressed TRH-stimulated TSH response by 27-35% between 40 min and 80 min in Test 4. In contrast, the pretreatment with PST completely reverted the suppressive effect of glucose on TRH-stimulated TSH response in Test 5. These data suggest that the increased hypothalamic SRIH secretion induced by oral glucose administration can suppress TRH-stimulated TSH response in normal men, and the combined glucose-TRH test can be a useful method to evaluate the hypothalamic somatostatinergic activity.

Adult↗

PubMed1996

The essential role of the functional group in alkyl isothiocyanates for inhibition of tobacco nitrosamine-induced lung tumorigenesis.

The importance of the isothiocyanate group in alkyl isothiocyanate for inhibition of tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK)-induce lung tumorigenesis was examined in A/J mice. Our previous structure-activity relationship study of isothiocyanates showed that 1-dodecyl isothiocyanate [CH3(CH2)11NCS], a simple alkyl isothiocyanate, is a potent inhibitor of NNK-induced lung tumorigenesis. It was chosen for this study due to its structural features and potency. A single dose of 1-dodecyl isothiocyanate given by gavage at 1 micromol/mouse 2 h prior to NNK administration completely inhibited lung tumorigenesis, while removal of the isothiocyanate group or replacing it with a hydroxyl group abolished the inhibitory activity. These results demonstrate that the isothiocyanate functional group is critical for the inhibitory activity of isothiocyanates in NNK-induced lung tumorigenesis. To gain more insights into the relationship of in vivo inhibition of tumorigenesis with the cytochrome P-450 enzyme inhibitory activity, the effects of these compounds on metabolism of NNK in mouse lung microsomes were studied. 1-Dodecyl isothiocyanate inhibited all three known oxidative pathways of NNK metabolism, with a stronger inhibitory activity toward NNK N-oxidation (IC50 430 nM) and keto alcohol formation (IC50 500 nM) than keto aldehyde formation (IC50 13,000 nM). 1-Dodecanol had a similar selectivity in inhibition of these metabolic pathways, but was less potent than 1-dodecyl isothiocyanate. Dodecane showed little or no inhibitory activity in the same concentration range. These results indicate that the isothiocyanate group of 1-dodecyl isothiocyanate is important for inhibition of NNK-induced lung tumorigenesis and also for effective inhibition of cytochrome P-450 enzymes involved in NNK oxidation.

Adenoma↗