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Biomedical subjects

D Kim

Publications and source records attributed to D Kim.

At least 271 records · Page 15Linked to original sources
PubMed1998

Experimental hypercholesterolemia induces ultrastructural changes in the elastic laminae of rabbit aortic valve.

Atherosclerosis is the most severe problem in the high-pressure systemic circulation and similar changes also occur in the high-pressure loading valve. This study was designed to test the hypothesis that early atherosclerosis, induced by a high cholesterol diet in rabbits, is characterized by significant ultrastructural change in the elastic laminae of the aortic valve. However, it is not known whether this process is also taking place in the cardiac valve at the early stage of atherosclerosis. Animals were fed either a high cholesterol diet (n = 5) or a control diet (n = 5) for 10-12 weeks. Histologic analysis demonstrated that subendothelial thickening and foam-cell infiltration were evident in the arterialis of aortic valves. Confocal microscopy revealed an altered pattern characterized by fragmentation and disorganization of the arterialis elastic laminae of hypercholesterolemic valves. Computerized digital analysis of the images obtained by confocal scanning microscopy demonstrated that compared to normal valves, the arterialis elastic laminae of hypercholesterolemic valves decreased in percentage of their elastin content (29.03 +/- 1.10% vs. 42.94 +/- 1.35%, p = 0.023). Immunohistochemical staining for matrix metalloproteinase-3 (MMP-3) revealed MMP-3 immunoreactivity was increased in hypercholesterolemic valves, predominantly in the arterialis. This study demonstrated that early atherosclerosis, induced by a high cholesterol diet in rabbits, is characterized by significant ultrastructural change in the elastic laminae of the aortic valve. The arterialis endothelium of the aortic valve may be a more atherosclerosis-prone area compared with the ventricularis. The presence of ultrastructural defect in the elastic laminae may play a role in chronic degenerative change and a resultant valvular dysfunction.

Animals↗
PubMed1998

Renal transplantation in a heterogeneous population: the thirty-year Montefiore Medical Center experience.

Based on more than 30 years of renal transplantation experience at Montefiore Medical Center we conclude: 1. Improved patient and graft survival can be achieved in the cadaveric transplant recipient despite increasing co-morbidities. 2. Patients at the extremes of age (< 10 or > 60) can undergo renal transplantation safely, with patient and graft survival rates approaching those of the general recipient population. 3. Results of transplantation in African-Americans are as good as non African-Americans at 3 years. Beyond that point the graft survival curves diverge. Well matched (0-1 HLA mismatches) kidneys in the African-American patient do as well if not better than other ethnic groups. However, African-Americans do not receive as many well matched kidneys as others.

Adolescent↗
PubMed1998

Does resuscitation produce a reperfusion injury?

Conceptually, shock with resuscitation should produce cellular changes that parallel those observed in a single organ exposed to ischemia with reperfusion, i.e., a transient worsening of the injury pattern after reperfusion with the degree of recovery reflecting the magnitude of the ischemic injury. To test this hypothesis, 74 male Sprague Dawley rats (300-400 g) were randomized into two groups with controls and exposed to 1) hemorrhagic shock (mean arterial pressure < 50 mm Hg) for 2 hours before sacrifice, or 2) shock (2 hours) with reinfusion of shed blood over 1 hour before sacrifice. Mean arterial pressure, blood loss, serum lactate, base excess, and bicarbonate were serially measured to determine the degree of tissue ischemia. At sacrifice, hepatic mitochondrial function was determined by the respiratory control ratio. Our findings were as follows: 1) Hemorrhagic shock produced significant (P < 0.001) tissue ischemia and impairment of mitochondrial function (P < 0.001), 2) resuscitation rapidly corrects the metabolic sequelae of tissue ischemia, and 3) mitochondrial function was unaffected by resuscitation. We conclude that resuscitation rapidly corrects the tissue ischemia associated with hemorrhagic shock, without producing any measurable reperfusion injury at the mitochondrial level.

Animals↗
PubMed1998

A placental-derived tissue matrix as a bowel wall substitute in rats: preliminary study.

BACKGROUND: Occasionally, conventional closure of an intestinal wall defect (fistula) is not possible. The development of a biologic material that can be used in this setting would solve a significant clinical problem. We hypothesized that a collagen patch (connective tissue matrix [CTM]) designed to allow tissue regeneration was such a material. METHODS: To test this hypothesis, we performed a laparotomy on 75 male Sprague-Dawley rats (experiment A) and removed 25% of the anterior cecal wall (1 cm in diameter) to compare intestinal wound healing in four situations: (1) control (no repair), (2) fibrin glue repair, (3) primary repair, and (4) repair with CTM (human placental bilayer, types I, III, and IV). Animals were killed at 1, 2, 4, and 6 weeks. Healing was graded by bursting pressure expressed in millimeters of mercury, histologic score (0 to 4), and mortality rates. After this, we used the same protocol to remove 80% of the cecal wall (1.5 x 2.0 cm) in 19 animals (experiment B) to compare (5) fibrin glue repair alone with (6) CTM repair in a situation in which the defect was too large for primary repair. RESULTS: CTM repair of a lethal cecal wall defect (experiment A) is equivalent to either primary repair or fibrin glue repair. When the defect is too large for primary repair (experiment B), repair with fibrin glue also does not work. However, in this same setting, CTM repair is successful (p < 0.00001). CONCLUSIONS: Intestinal wall defects not suitable for conventional closure can be repaired successfully with a collagen patch, with histologic characteristics similar to those seen with primary repair.

Animals↗
PubMed1998

Nonsyndromal craniosynostosis: longitudinal outcome following cranio-orbital reconstruction in infancy.

This paper presents a prospective longitudinal outcome study on patients with nonsyndromal craniosynostosis who were treated with the contemporary craniofacial surgical techniques of suture release, cranial decompression, and cranial and orbital reconstruction and reshaping in infancy. Diagnosis, surgical treatment, and long-term results and complications are reviewed. Preoperative and long-term postoperative intracranial volumes in these patients were evaluated and compared with age and gender match controls throughout the period of the study. From July 1, 1990, to July 1, 1994, 25 patients with isolated nonsyndromal craniosynostosis underwent surgery of the deformity. Eight patients were excluded from the study based on incomplete postoperative computed tomography (CT) records. Of the 17 patients with long-term computerized records, 11 were boys and 6 were girls. The nonsyndromal craniosynostosis patients in this study include six with bilateral coronal craniosynostosis, six with unilateral coronal craniosynostosis, four with sagittal craniosynostosis, and one with metopic craniosynostosis. The average age at the time of surgery for all patients was 9 months, and the average age at the time of the latest follow-up CT scan for all patients in the study was 3.5 years. There were no perioperative complications in this series of patients including no bleeding, no infection, no wound healing complications, and no mortality. Bony fixation included a combination of wire osteosynthesis and rigid microfixation. All patients had only one surgical procedure for the correction of their deformity. Evaluation of both preoperative and long-term postoperative intracranial volume measurements in this series of patients revealed that these volume measurements were comparable with the gender match control groups at all ages throughout the study. The significance of these findings for this longitudinal outcome study is discussed.

Cephalometry↗
PubMed1997

Contrasting roles for symmetrically disposed beta-turns in the folding of a small protein.

To investigate the role of turns in protein folding, we have characterized the effects of combinatorial and site-directed mutations in the two beta-turns of peptostreptococcal protein L on folding thermodynamics and kinetics. Sequences of folded variants recovered from combinatorial libraries using a phase display selection method were considerably more variable in the second turn than in the first turn. These combinatorial mutants as well as strategically placed point mutants in the two turns had a similar range of thermodynamic stabilities, but strikingly different folding kinetics. A glycine to alanine substitution in the second beta-turn increased the rate of unfolding more than tenfold but had little effect on the rate of folding, while mutation of a symmetrically disposed glycine residue in the first turn had little effect on unfolding but slowed the rate of folding nearly tenfold. These results demonstrate that the role of beta-turns in protein folding is strongly context-dependent, and suggests that the first turn is formed and the second turn disrupted in the folding transition state.

Bacterial Proteins↗
PubMed1997

Phospholipase C isozymes selectively couple to specific neurotransmitter receptors.

A variety of extracellular signals are transduced across the cell membrane by the enzyme phosphoinositide-specific phospholipase C-beta (PLC-beta) coupled with guanine-nucleotide-binding G proteins. There are four isoenzymes of PLC-beta, beta1-beta4, but their functions in vivo are not known. Here we investigate the role of PLC-beta1 and PLC-beta4 in the brain by generating null mutations in mice: we found that PLCbeta1-/- mice developed epilepsy and PLCbeta4-/- mice showed ataxia. We determined the molecular basis of these phenotypes and show that PLC-beta1 is involved in signal transduction in the cerebral cortex and hippocampus by coupling predominantly to the muscarinic acetylcholine receptor, whereas PLC-beta4 works through the metabotropic glutamate receptor in the cerebellum, illustrating how PLC-beta isoenzymes are used to generate different functions in the brain.

Animals↗
PubMed1997

The clinical use of erythrocyte sedimentation rate in pyogenic vertebral osteomyelitis.

STUDY DESIGN: Retrospective chart review of 44 cases. OBJECTIVE: To describe the clinical usage of the erythrocyte sedimentation rate in pyogenic vertebral osteomyelitis. SUMMARY OF BACKGROUND DATA: The erythrocyte sedimentation rate is often used to determine the efficacy and duration of treatment in pyogenic vertebral osteomyelitis. Although consensus and anecdotal reports support this notion, no detailed review of the erythrocyte sedimentation rate response in conservative treatment of pyogenic vertebral osteomyelitis has been made, to date. METHODS: For 44 patients with pyogenic vertebral osteomyelitis who had erythrocyte sedimentation rate testing at or before the time of diagnosis and at least twice during the next month, the clinical findings and results of the erythrocyte sedimentation rate testing were reviewed. RESULTS: Of 18 cases with no significant fall in the erythrocyte sedimentation rate during the first month, 9 (50%) failed conservative treatment. Conversely, of the 26 cases with a good erythrocyte sedimentation rate response during the first month, three (12%) were clinical failures. However, a rapid decline of the erythrocyte sedimentation rate (> 50% in the first month) is rarely seen in treatment failure. In addition, approximately 2 weeks after antibiotic treatment, 19 of 32 were actually higher than at the time of diagnosis, but went on to clinical cure without surgery. The erythrocyte sedimentation rate, in combination with the patient's age and immune status, predicted the success of antibiotic treatment, in most cases. The erythrocyte sedimentation rate response alone during the first month was not a clear predictor of success. CONCLUSIONS: Although the erythrocyte sedimentation rate does correlate well with response to treatment as a general rule, care must be taken in interpretation of a persistently elevated or even rising erythrocyte sedimentation rate as an isolated clinical finding.

Adolescent↗
PubMed1997

Expression of transforming growth factor beta type II receptor reduces tumorigenicity in human gastric cancer cells.

Expression of transforming growth factor beta (TGF-beta) receptor type II (RII) is required for the growth-inhibitory effects of TGF-beta on proliferating epithelial cells. TGF-beta RII mutations have been identified in a broad spectrum of human epithelial malignancies, including colon and gastric cancers, and are highly correlated with development of TGF-beta resistance in cell lines derived from these tumors. In this study, the role of TGF-beta RII in regulating the tumorigenic potential of the SNU-638 human gastric cancer cell line was investigated by infecting these cells with retroviral construct (MFG) expressing TGF-beta RII. The SNU-638 cell line displays the DNA replication error phenotype and encodes a truncated, inactive TGF-beta RII protein. Infection of these cells with retroviral constructs expressing wild-type TGF-beta RII led to significant increases in TGF-beta RII mRNA and protein expression. These cells responded to exogenous TGF-beta with reduced proliferation compared to that of control cells infected with retroviral vector expressing chloramphenicol acetyltranferase. Addition of TGF-beta-neutralizing antibodies led to increased proliferation of wild-type TGF-beta RII-expressing SNU-638 cells but had no effect on control cells. The latter finding suggests that TGF-beta acts in an autocrine fashion to inhibit cell proliferation in SNU-638 cells. When transplanted into athymic nude mice, wild-type TGF-beta RII-expressing SNU-638 cells showed decreased and delayed tumorigenicity compared with control cells. This study suggests a strong association between the expression of wild-type TGF-beta RII and the degree of malignancy in human gastric cancer cells.

Animals↗
PubMed1997

Involvement of soluble proteinous factors in auxin-induced modulation of P-type ATPase in rice (Oryza sativa L.) seedlings.

The marked difference in auxin sensitivity between plant roots and shoots was studied in terms of auxin-induced stimulation of membrane P-type ATPase. The results suggest the existence in rice seedlings of, at least, two isoforms of soluble proteinous factors (SPF), SPF(I) and SPF(II), which are involved in the stimulatory action of auxin on the enzyme. It also is indicated that SPF(I) which mediates the auxin effect in low hormone concentration range (10(-10)-10(-7) M IAA) is the dominant isoform in roots, whereas SPF(II) which does in high hormone concentration range (10(-7)-10(-4) M IAA) is that in shoots.

Adenosine Triphosphatases↗
PubMed1997

Noninvasive comprehensive characterization of renal artery stenosis by combination of STAR angiography and EPISTAR perfusion imaging.

In a small fraction of patients with hypertension, the cause is stenosis of the renal artery. To date, there is no established noninvasive screening technique available to identify this population, for whom treatment with a surgical procedure or percutaneous transluminal angioplasty is often possible. In this study, the sensitivity and specificity of STAR angiography and EPISTAR perfusion imaging in characterizing renal artery stenosis were evaluated in an animal model. Qualitatively, STAR provided projection angiograms that were comparably sensitive to x-ray angiograms but obtained noninvasively. The sensitivity for detecting the stenosis was 100%. The specificity varied according to the definition of the threshold for significance, which varied 78-94%, depending on whether > 70% or > 50% diameter reduction was considered. Improvements in specificity will depend upon use of shorter echo times and higher spatial resolution. Our preliminary data indicate that EPISTAR provides sensitivity and specificity of 100% for characterizing stenosis with diameter reductions of > 70%.

Animals↗
PubMed1997

A solenoid-like coil producing transverse RF fields for MR imaging.

A solenoidal RF coil is presented that generates an RF field only perpendicular to the long axis, so that it can be used longitudinally in the usual superconducting solenoid magnet for NMR. This new design is superior to the traditional saddle coil or Helmholtz pair. Applications for the coil will include imaging of legs, arms, etc., as well as analytical application in high-resolution NMR. A tilted single-turn-solenoid, which has the plane of each loop tilted with respect to the cylinder axis, is implemented to generate an RF field with a component perpendicular to the coil-cylinder axis. The novel addition of an eddy-current coil eliminates the undesirable longitudinal component of the RF field, leaving an RF field entirely perpendicular to the coil-cylinder axis. By inserting the eddy coil, the spatial homogeneity of the transverse RF field is greatly improved, with significant increases in the H1 field strength and receiving sensitivity. Images with the eddy-coil-modified tilted solenoid are remarkably uniform in intensity over a large useful volume.

Hand↗
PubMed1997

Novel neuropeptide Y receptor antagonists block vasoconstriction in the hamster cheek pouch microcirculation.

We investigated the efficacy of novel neuropeptide Y (NPY) antagonists to inhibit the microcirculatory dynamics of NPY in the hamster cheek pouch microcirculation using intravital microscopy and computer-assisted image analysis. Changes in arteriolar diameter served as an index of vasomotor alterations. Fluorescein isothiocyanate-labeled Dextran 150 served as a tracer for measurements of macromolecular transport. GW 383 and GW 1229, two novel NPY receptor antagonists, were applied topically in separate experiments. Pretreatment with 10(-5), 10(-6) and 10(-7) M GW 383 and with 10(-6) and 10(-8) M GW 1229 attenuated the vasoconstriction induced by 10(-7) M NPY in a dose-dependent manner. Furthermore, pretreatment with 10(-7) and 10(-8) M GW 1229 significantly inhibited the 10(-9) M NPY-induced vasoconstriction. At these doses, the NPY antagonists did not alter microvascular permeability. Our results demonstrate that the novel NPY antagonists inhibit the vasoconstriction induced by NPY in the hamster check pouch microcirculation. We suggest that the inhibition is due to binding of antagonists to Y1-type NPY receptors.

Animals↗
PubMed1997

Endothelin and atrial natriuretic peptide levels following radiocontrast exposure in humans.

Radiocontrast exposure is associated with vasoconstriction of the renal vascular bed and, in certain circumstances, with acute renal failure. This may be influenced by the volume of contrast infused or underlying disease, such as diabetes or renal failure. Changes in circulating vascular regulators, such as endothelin and atrial natriuretic peptide (ANP), may play a role in the development and/or prevention of acute renal failure. Nineteen patients undergoing arteriographic procedures were divided into two groups: large-volume contrast (> or = 150 mL; n = 7) and small-volume contrast (< 150 mL; n = 12). Circulating endothelin levels increased significantly (from 12.3 +/- 1.1 pmol/L to 19.4 +/- 2.2 pmol/L; P < 0.05) following large-volume contrast exposure (group 1) but not following small-volume contrast exposure (group 2) (13.9 +/- 1.7 pmol/L to 12.2 +/- 0.09 pmol/L). ANP levels increased significantly in both groups: 43 +/- 15 pg/mL to 75 +/- 21 pg/mL in group 1 and 33 +/- 16 to 106 +/- 39 pg/mL in group 2. Data from an additional eight patients with underlying diabetes mellitus and/or renal insufficiency also were obtained and were considered separately. Endothelin levels were higher at baseline and increased significantly after contrast (25.7 +/- 5 pmol/L to 55.4 +/- 18 pmol/L) despite the relatively small average volume of contrast infused (112 +/- 15 mL). ANP levels were also highest in these patients (211 +/- 43 pg/mL precontrast and 323 +/- 65 pg/mL postcontrast). No group had a significant change in serum creatinine following contrast exposure. In conclusion, large-volume radiocontrast exposure is associated with an increase in both circulating endothelin and ANP levels. Patients with underlying diabetes or renal insufficiency may have higher baseline levels and a greater tendency to increase endothelin after contrast exposure. While an increase in endothelin may contribute to renal vasoconstriction following radiocontrast exposure, simultaneous increases in ANP may serve to offset this response and protect against changes in renal function.

Adult↗
PubMed1997

Pruritus in chronic hepatitis C: association with high serum bile acids, advanced pathology, and bile duct abnormalities.

Pruritus is a common symptom of chronic cholestatic liver diseases but is considered rare in chronic hepatitis. We observed pruritus to be an unusually common complaint in patients with advanced chronic hepatitis C. We reviewed the records of 175 chronic hepatitis C patients to identify patients with severe, diffuse, unexplained pruritus; 12 consecutive prospective patients undergoing liver biopsy for chronic hepatitis C served as controls. Assessment included laboratory biochemical tests and assessment of liver pathology by stage, grade, hepatic activity index, and a bile duct score. Pruritus was present in nine (5.1%) patients. Serum AST, ALT, alkaline phosphatase, GGTP, total bilirubin, and ferritin were similar in pruritics and controls. Pruritics had higher serum bile acids (2028.4 +/- 223.1 mmol/liter vs 423.1 +/- 194.3, P < 0.001), higher transferrin saturation (57.5 +/- 6.8% vs 33.2 +/- 3.3, P < 0.01), and lower HCV RNA by bDNA (24.5 +/- 12.7 x 10(5) vs 172.7 +/- 54.1 x 10(5), P < 0.05). Pathology revealed cirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P < 0.01). Pruritics had higher pathologic stage (3.7 +/- 0.2 vs 2.2 +/- 0.4, P < 0.01), grade (4.4 +/- 0.2 vs 2.1 +/- 0.2, P < 0.001), activity index (14.3 +/- 1.9 vs 8.6 +/- 1.9, P < 0.025), and bile duct score (7.6 +/- 0.6 vs 4.7 +/- 0.4, P < 0.01). Of eight pruritics treated with IFN-alpha2b, two had complete ALT response and one relapsed. Pruritus followed a relapsing course and only three patients partially responded despite a variety of interventions. In conclusion, pruritus is a common complication of advanced CHC. Its presence is associated with high serum bile acids, advanced pathology and bile duct abnormalities. The clinical course of pruritus is relapsing and response to therapy is inconsistent. These features suggest that pruritus in CHC has a pathogenesis that may vary from that of chronic cholestatic diseases.

Antiviral Agents↗
PubMed1997

Identification of PAHX, a Refsum disease gene.

Refsum disease is an autosomal recessive disorder characterized by retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia and increased cerebrospinal fluid protein. Biochemically, the disorder is defined by two related properties: pronounced accumulation of phytanic acid and selective loss of the peroxisomal dioxygenase required for alpha-hydroxylation of phytanoyl-CoA2. Decreased phytanic-acid oxidation is also observed in human cells lacking PEX7, the receptor for the type-2 peroxisomal targetting signal (PTS2; refs 3,4), suggesting that the enzyme defective in Refsum disease is targetted to peroxisomes by a PTS2. We initially identified the human PAHX and mouse Pahx genes as expressed sequence tags (ESTs) capable of encoding PTS2 proteins. Human PAHX is targetted to peroxisomes, requires the PTS2 receptor for peroxisomal localization, interacts with the PTS2 receptor in the yeast two-hybrid assay and has intrinsic phytanoyl-CoA alpha-hydroxylase activity that requires the dioxygenase cofactor iron and cosubstrate 2-oxoglutarate. Radiation hybrid data place PAHX on chromosome 10 between the markers D10S249 and D10S466, a region previously implicated in Refsum disease by homozygosity mapping. We find that both Refsum disease patients examined are homozygous for inactivating mutations in PAHX, demonstrating that mutations in PAHX can cause Refsum disease.

Amino Acid Sequence↗
PubMed1997

Relative effects of aging and age-related macular degeneration on peripheral visual function.

The purpose of this study was to determine the extent of peripheral visual deficits in patients with early age-related macular degeneration (ARMD) using electrophysiological and psychophysical techniques. Dark-adaptation curves, electro-oculograms (EOGs), and electroretinograms (ERGs) were obtained from patients with early ARMD and from normally sighted control subjects. The control subjects' data were used to calculate age-dependent 95% confidence intervals for each measure of visual function. For the control subjects, performance on all our measures of visual function decreased with age. For the patients with early ARMD, the cone system absolute thresholds, EOG ratios, and cone-dominated ERG amplitudes and implicit times were within the range of normal age-related changes. Rod system absolute thresholds, cone-rod break times, and rod-dominated electroretinographic measures were abnormal in some patients. These results suggest that when the effects of aging are taken into account, some patients classified as early ARMD may not show significant changes in peripheral retinal function with standard clinical tests.

Aged↗