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Biomedical subjects

P Kim

Publications and source records attributed to P Kim.

At least 73 records · Page 4Linked to original sources

Binding preferences of the POU domain protein Brain-4: implications for autoregulation.

The POU domain-containing transcription factor Brain-4 (Brn-4, RHS-2) was examined for its sites of expression and DNA binding preferences. In the rat, Brn-4 is expressed in 76 and 65% of vasopressin neurons in the paraventricular and supraoptic nuclei, respectively; but in only 10% of corticotropin-releasing factor neurons in the paraventricular nucleus of the hypothalamus. From these data we speculate that genes expressed within vasopressinergic neurons are more likely to be regulated by Brn-4 than those in corticotropin-releasing factor neurons. Random oligonucleotide site selection indicates Brn-4 prefers binding the DNA element CAATATGCTAAT and is inflexible in its spacing requirement between putative CAATAT and TAAT half sites, preferring 2 nucleotides between these elements. Electrophoretic mobility shift and DNase I footprinting analyses show five regions between nucleotides -457 and +22 of the Brn-4 promoter that are bound by Brn-4. Furthermore, Brn-4 can transactivate from this region of the Brn-4 promoter, suggesting that Brn-4 expression may be autoregulated.

Adenine↗

A 45-year experience with surgical treatment of peptic ulcer disease in children.

Peptic ulcer disease (PUD) requiring surgical treatment has become rare with the availability of modern medical management. A retrospective study of all patients who required operations for PUD between 1949 and 1994 (n = 43) was done. The patients were classified into 3 groups: A (n = 38): pre-histamine-2 (H2) blocker era (1949-1975); B (n = 3): pre-hydrogen-potassium (H-K+) ATPase inhibitor era (1976-1988); C (n = 2): H-K+ ATPase inhibitor era (1989-1994). Data, analyzed using X2 analysis (P < .01), included preoperative medical therapy, surgical indications, type of operation performed, complications, and postoperative medical therapy. The indication for surgery in group A was bleeding (26), perforation (8), or obstruction (4); in group B the indication was obstruction (2) or perforation (1); in group C the indication was obstruction (1) or bleeding (1). The incidence of obstruction as an indication for surgery did not differ among the groups (P < .01). Two of the three patients who had surgery for obstruction in groups B and C had biopsy-proven Helicobacter pylori. The postoperative morbidity rate was lower for groups B and C, although not significantly. The relative mortality among the groups did not change (P > .01). Children with PUD can have complications similar to those of adults with PUD. Since the introduction of H2 antagonists, the recognition and treatment of H pylori, and the use of H-K+ ATPase inhibition, the incidence of operations for bleeding and perforation has decreased dramatically. However, the incidence of surgery for obstruction remains the same.

Anti-Ulcer Agents↗

What is the best way of assessing outcome after total knee replacement?

Variable definitions of outcome have been used in the past to assess the results after total joint replacement surgery. These differ in their approach to the measurement of outcome but all must be valid (they measure what they are designed to measure), reliable (they consistently produce the same score), and responsive (able to detect changes that may occur during a period). Responsiveness is crucial to distinguish those patients who benefit from a procedure from those who do not, and a more responsive test will theoretically be able to identify more subtle changes in patient status. The responsiveness of 6 different scoring systems was compared. The results are based on a cohort of 71 patients undergoing total knee arthroplasty in a 7-month period. Responsiveness was determined by performing a paired t test among each patient's scores at 0, 3, and 6 months. The size of the resulting t value represented the comparative responsiveness of the 6 tests. The highest value achieved was with the Western Ontario and McMaster Universities osteoarthritis index and the Knee Society clinical rating scale. The worst scores were achieved by Short Form-36 and time trade off, a utility method of measurement. If small differences between groups of patients are to be shown, measures of outcome that are more responsive to patient change should be used.

Activities of Daily Living↗

Impaired calcium regulation of smooth muscle during chronic vasospasm following subarachnoid hemorrhage.

The intracellular calcium level was determined in the canine basilar artery to investigate whether Ca2+ regulation of its smooth muscle is altered during chronic vasospasm following subarachnoid hemorrhage. A double-hemorrhage model was used. The occurrence of vasospasm was confirmed angiographically 7 days after initial hemorrhage. The intracellular calcium concentration ([Ca2+]i) of smooth muscle was measured using Fura-2. Fluorescence to excitation at 340 and 356 nm was monitored and the ration R340/356 was used as the indicator of [Ca2+]i. When the extracellular calcium concentration ([Ca2+]e) was increased from pCa 8 to 2, [Ca2+]i also increased. In the spastic arteries, the [Ca2+]e - [Ca2+]i curve was elevated as compared with the normal arteries. Treatment with ionomycin elevated the curve in the normal group, but it had little effect in the spastic arteries. Values of [Ca2+]i, calculated in multiples of Kd, were greater in the spastic arteries. Diltiazem (10(-5) mol/L) partially suppressed the augmented [Ca2+]i signal in the spastic arteries, whereas it did not affect the curve in the control group. These results indicate that the calcium regulation of smooth muscle is impaired after subarachnoid hemorrhage, which may contribute to the pathogenesis of chronic vasospasm.

Animals↗

Intramedullary angiographically occult vascular malformations of the spinal cord.

OBJECTIVE: This study was performed to elucidate the differences between angiographically occult vascular malformations of the spinal cord and the histological subtypes. METHODS: The cases of six patients with spinal intramedullary angiographically occult vascular malformations encountered during the past 10 years were examined regarding clinical course, neuroradiological manifestations, and surgical consideration. RESULTS: There were four cavernous malformations and two arteriovenous malformations. The cervical section of the spinal cord was involved in four cases, and the thoracic section of the spinal cord was involved in two. All of the patients had presented with motor weakness and sensory disturbance below the level of the lesion. Two distinct clinical courses were observed; they were neurological decline with repeated episodes of relapse and remission (four patients) and continuing neurological decline (two patients). Although a mixed-intensity core surrounded by a low-intensity rim is thought to be characteristic of cavernous malformations, we were not able to differentiate the histological types on the basis of magnetic resonance imaging findings alone. CONCLUSION: In cases of spinal intramedullary angiographically occult vascular malformations, even if clinical course and magnetic resonance imaging findings are consistent with cavernous malformation, other histological subtypes need to be considered. Surgery should be considered for symptomatic patients, because symptoms and signs that are probably caused by bleeding tend to worsen rather than stabilize.

Adolescent↗

AgNOR quantity in needle biopsy specimens of prostatic adenocarcinomas: correlation with proliferation state, Gleason score, clinical stage, and DNA content.

Aims-To define the relation between the quantity of silver stained nucleolar organiser regions (AgNORs) and histological grade, clinical stage, DNA content, and MIB-1 immunostaining in needle biopsy specimens of prostatic adenocarcinomas.Methods-Histological grade was determined according to the Gleason system. AgNOR quantity, DNA content and MIB-1 immunostaining were evaluated by image cytometry on routine histological sections stained with silver, Feulgen reaction and MIB-1 antibody, respectively.Results-The mean AgNOR area increased with increasing Gleason score. A significant difference was found in the AgNOR values between low, intermediate and high grade tumours. Patients with clinically localised tumour (stages A and B) had lower AgNOR values than patients with advanced disease (stages C and D), but the difference in the mean AgNOR values between the two groups was not statistically significant. Non-diploid tumours had a significantly higher mean (SD) AgNOR area than diploid tumours (3.68 (1.04) mum(2)v 2.73 (0.60) mum(2), respectively), while no significant difference was observed in the mean AgNOR values between aneuploid and tetraploid tumours (3.68 (1.04) mum(2)v 3.70 (1.05) mum(2)). When AgNOR and MIB-1-PI values were compared using linear regression analysis, a highly significant correlation was found.Conclusions-These data demonstrate that AgNOR quantity reflects the proliferative potential of prostatic adenocarcinomas, and is significantly related to histological grade and DNA content. The ease of application on routine sections, maintaining the morphological integrity of the tissue, the ability to evaluate selected histological areas of limited size and objective quantification by image cytometry make the AgNOR method particularly suitable for cell kinetic analysis in prostatic needle biopsy specimens.

Journal Article↗

Crohn's disease and acute leukocytoclastic vasculitis of skin.

A 39-yr-old white male with a prolonged history of Crohn's disease presented with worsening diarrhea associated with an increasingly painful rash of both lower extremities as well as left ankle swelling. A skin biopsy revealed an acute leukocytoclastic vasculitis. Intravenous hydrocortisone followed by oral prednisone achieved a rapid remission of the both cutaneous and gastrointestinal manifestations. Long-term remission has been maintained with 6-mercaptopurine and mesalamine. The rare association between cutaneous vasculitis and Crohn's disease is discussed and earlier reported cases reviewed.

Adult↗

Nonsurgical delay of skin flaps: effect of a suture delay technique on blood flow and survival.

Surgical delay is the only clinical means of improving survival of skin flap tissue, but it has inherent risks and costs of a surgical procedure. This study tested the hypothesis that any method of disrupting the circulation at the distal perimeter of a planned skin flap would induce collateral circulation from the base of the flap and thereby improve flap survival. The suture delay technique was performed on rats, and two outcome measures were used: blood flow patterns and skin flap survival. Blood flow patterns were tested before and after the suture technique by means of the base occlusion test. Flap survival in the suture delay group was compared with survival in acute and surgical delay control groups. Flap survival in the suture delay group (95.6% +/- 0.6%, n = 22) was significantly greater than in the acute control group (85.7% +/- 1.6%, n = 22) and was not different from that in the surgical delay model (95.2% +/- 0.5%, n = 21). Laser Doppler studies demonstrated a change in blood flow patterns. This study supports the theory that the mechanism of the delay phenomenon is the development of collateral blood from the base of the flap and suggests that the benefits of delay can be achieved with minimal surgical trauma.

Animals↗

Functional changes in cultured strips of canine cerebral arteries after prolonged exposure to oxyhemoglobin.

The present study was undertaken to determine whether oxyhemoglobin (OxyHb) is responsible for the functional alterations in the cerebral arteries observed during chronic vasospasm after subarachnoid hemorrhage. Vascular strips of canine basilar arteries were kept in organ culture for 3 days with or without repetitive exposure to OxyHb (OxyHb-treated and control strips). Contractions elicited by high levels of potassium (80 mM) and uridine 5'-triphosphate (3 x 10(-4) M) were reduced in the OxyHb-treated group in a concentration-dependent manner. The relaxations evoked by nitric oxide and 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP) were not affected. Relaxations elicited by the calcium channel blocker, diltiazem, were attenuated in the OxyHb-treated rings. When the extracellular calcium concentration ([Ca2+]e) was changed from a concentration in the external solution of 10(-8) M to 10(-3) M, myogenic tension developed. Myogenic tension, expressed as a percentage of the maximum contraction in each segment, was augmented in the OxyHb-treated group at [Ca2+]e of 10(-5) M and 10(-4) M. There were no significant differences in passive compliance of the arterial wall between the two groups. These results demonstrated that prolonged exposure to OxyHb in vitro results in a decrease in contractile capacity and an increase in sensitivity to [Ca2+]e, in agreement with previous findings in spastic arteries. By contrast, impairment of the 8-bromo-cGMP-mediated relaxation pathway and increased stiffness of the arterial wall, which have been reported to occur in spastic arteries, were not induced by prolonged exposure to OxyHb in vitro.

Analysis of Variance↗

Selective inhibition of glutamate uptake by mercury in cultured mouse astrocytes.

We studied the effects of organic and inorganic mercury (Hg) on the uptake of L-[3H] glutamate (L-GLU) in cultured mouse astrocytes. Following exposure to mercuric chloride (MC) [0.2 approximately 5.0 microM], selective and dose-dependent inhibition of L-GLU uptake to 50% of control levels was observed, whereas 2-deoxyglucose (2-DG) uptake was not significantly affected. Methylmercuric chloride (MMC) also inhibited L-GLU uptake but 50% reduction was reached only at a concentration of 10 microM. Inhibition of L-GLU uptake by MMC appears to be closely linked to voltage-sensitive calcium channels as evidenced by the lack of L-GLU uptake inhibition by MMC in calcium-free medium or in the presence of the channel blocker verapamil. Exposure to a variety of divalent metallic ions, including CuCl2, FeCl2 and ZnCl2, did not affect L-GLU uptake in astrocytes in vitro. Exposure to PbCl2, however, resulted in a decline in L-GLU uptake, though to a much smaller degree than that observed with Hg compounds. Selective impairment of astroglial L-GLU transport may represent a critical early pathogenetic feature of Hg-induced neurotoxicity.

Animals↗

Violence victims' perception of functioning and well-being: a survey from an urban public hospital walk-in clinic.

This study assessed the health perceptions of self-reported violence victims in an urban minority population attending a walk-in clinic by using an anonymous, 1-week, cross-sectional survey. The Medical Outcome Study Short-Form (MOS SF-20) was used to assess functioning/well being, including the dimensions of physical functioning, role functioning, social functioning, mental health, health perceptions, and pain. Health perception main scores were calculated for each of the six health dimensions in the following four groups: patient-victims, patient-nonvictims, visitor-victims, and visitor-nonvictims. Odds ratios (OR) were calculated to assess the association of violence victimization and functioning/well-being. The mean scores of health status were consistently better among nonvictims for all of the six health concepts measured; patients who were victims showed lower mean scores than nonvictim patients. A similar pattern also was found in visitors' health status scores when victims were compared to nonvictims. The strongest association was found between violence victimization and mental health, and the least association was between the pain score and violence victimization. This study showed a substantial association between poor health and violence victimization in the patient population studied. Intervention is needed to prevent and decrease violence in order to minimize the impact of violence on the health of victims.

Chicago↗

Imaging of individual normal and regenerating optic fibers in the brain of living adult goldfish.

Retinal arbors in the tectum of living adult goldfish were imaged to determine whether the structural remodelling and refinement that occurs during development continues in adulthood. Individual optic fibers were labelled by making small injections of the lipophilic fluorescent dye DiI into ventral retina and viewing the exposed tectum through a fluorescence microscope equipped with a cooled CCD camera. Arbors were imaged in the living fish every 30-60 minutes for up to 7 hours. Normal adult goldfish showed no evidence of arbor remodelling during this period, though dynamic movements of varicosities present along axon segments were observed. For comparison, regenerating optic fibers were similarly imaged in fish that had undergone optic nerve crush 2-6 weeks previously. In these fish, dynamic structural changes were seen, including branch remodelling, extension and retraction of growth cones, and movement of varicosities.

Animals↗

Community-based perinatal care for disadvantaged adolescents: evaluation of The Resource Mothers Program.

This study compared the effects of a community-based lay home visiting initiative for pregnant adolescents, the Norfolk Resource Mothers Program, with the effects of a more traditional clinic-based program. The Resource Mothers Program (RMP) supports disadvantaged teens through the use of para-professional home visitors who are similar to the teens in race and socio-economic status. In addition to recruiting teens into the program and encouraging early prenatal care, the Resource Mothers Program provides teen mothers and their families with practical help and increases community awareness regarding infant mortality and adolescent pregnancy. When compared with a traditional clinic-based multi-disciplinary program (MDP) using health professionals, the Resource Mothers Program reached a higher percentage of high-risk adolescents (e.g., 75.5% RMP vs. 45.6% MDP clients aged 17 years old or under), promoted a higher level of prenatal care (e.g., 53.1% RMP vs. 32.6% MDP clients beginning prenatal care before the fourth month of pregnancy), and resulted in pregnancy outcomes that favored the MDP but were comparable (e.g., 89.8% RMP vs. 93.5% MDP client babies were over 2500 grams at birth).

Adolescent↗

Prevalence of violence victimization among patients seen in an urban public hospital walk-in clinic.

OBJECTIVES: To study the prevalence of serious physical interpersonal violence and to identify the types of perpetrators, the frequency of occurrence, the time since the violence occurred, the risk profiles, and other factors related to victimization. METHODS: One-week survey of all consecutively registered patients and their visitors in an urban public hospital adult walk-in clinic, using an anonymous self-administered questionnaire. RESULTS: Of the 1,504 patients, 1,041 (69.2%) completed the questionnaire. The reported experience of serious physical violence victimization for the whole study population, both patients (n = 1,041) and visitors (n = 155), was 47.9% (573/1,196). A violence victim was more likely to be male [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.11, 1.78], African-American (OR = 1.27, 95% CI: 0.98, 1.63), aged 45 years or younger (OR = 1.55, 95% CI: 1.19, 2.03), and single (OR = 1.47, 95% CI: 1.16, 1.86). Alcohol use and drug use were clearly associated with violence victimization, with prevalence ORs of 2.26 (95% CI: 1.80, 2.85) for alcohol and 3.68 (95% CI: 2.66, 5.09) for drugs. CONCLUSION: A history of serious physical violence victimization is common in inner-city hospital walk-in clinic patients. Walk-in clinics in urban areas of high violence, therefore, may prove to be important places for intervention and prevention of violence.

Adult↗

Loss of relaxations, metabolic failure and increased calcium permeability of smooth muscle during chronic cerebral vasospasm.

In the canine basilar artery during chronic vasospasm following subarachnoid hemorrhage, endothelium-dependent relaxations were diminished. Release of endothelium-derived relaxing factor (EDRF), as measured by a bioassay method, was unchanged. Relaxation to nitric oxide (NO) in preparations without endothelium was smaller in the spastic arteries. Production of cyclic GMP, measured by radioimmunoassay, was reduced in the spastic arteries; the impaired production was accompanied by decrease in GTP, the substrate for the production of cyclic nucleotide. The contents of other high-energy phosphates, such as creatine phosphate and ATP were also markedly reduced. Close temporal correlation between the metabolic failure and development of vasospasm was observed. Sarcolemmal regulation of intracellular calcium concentration was impaired in the pathological condition, suggesting a link between the metabolic failure and the pathological protracted contractions. Metabolic changes, and resultant affected viability of smooth muscle cells are likely to be an important factor in the pathogenesis of chronic vasospasm.

Adenosine Triphosphate↗

Further characterization of an amsacrine-resistant line of HL-60 human leukemia cells and its topoisomerase II. Effects of ATP concentration, anion concentration, and the three-dimensional structure of the DNA target.

The characterization of type II topoisomerases from amsacrine-sensitive (HL-60) and amsacrine-resistant (HL-60/AMSA) human leukemia cells was extended. The intercalator resistance and etoposide sensitivity of the HL-60/AMSA cells themselves were confirmed, and the stability of this pharmacologic phenotype over many hundreds of cell generations was demonstrated. Prolonging exposure of HL-60/AMSA cells to amsacrine did not alter their sensitivity relative to that of HL-60 cells. Improved methods of immunoblotting allowed clear demonstration that the topoisomerase II within these cells exhibited sensitivity and resistance characteristics that mirrored those of the cells and the isolated enzymes themselves. Additional biochemical characterization of the type II topoisomerases indicated that both enzymes relaxed supercoiled DNA in a distributive fashion and that the ATP concentrations at which optimal catalytic activity of the two enzymes was exhibited were identical. The enzymes differed, however, in their activity optima in buffers of various type and ionic strength. Furthermore, the inability of the HL-60/AMSA enzyme to exhibit enhanced DNA cleavage in the presence of amsacrine could be overcome if the DNA target molecule contained a bend cloned into its polylinker region. By contrast, a bend in a DNA plasmid containing no polylinker was resistant to amsacrine-enhanced cleavage in the presence of HL-60/AMSA topoisomerase II, as was a plasmid containing a polylinker with no bend. This suggests that an unusual DNA conformation (a bend) in a specific DNA context (a polylinker) may be a favored site for topoisomerase II action. It also suggests a mechanism by which the sites and extent of topoisomerase II activity can be controlled in cells.

Adenosine Triphosphate↗

Polarized secretion of thrombospondin is opposite to thyroglobulin in thyroid epithelial cells.

In addition to thyroglobulin, primary thyrocytes secrete into the culture medium significant quantities of p500, a protein so named because of its M(r) > or = 500,000. Epithelial monolayers cultured on porous filters serve as a useful model system in which to study protein secretion. From these monolayers, thyroglobulin, the precursor in thyroid hormonogenesis, was released with apical predominance, while p500 was found mostly in the basolateral medium. Thyrocyte exposure to thyrotropin augmented selectively thyroglobulin but not p500 production. By contrast, exposure to cycloheximide actually augmented p500 production, a response observed for immediate-early proto-oncogenes. Using thyrocyte conditioned medium, the p500 protein was purified to homogeneity. Peptide sequencing of tryptic fragments of purified p500 showed identity to thrombospondin. Immunoprecipitation of thrombospondin from media bathing primary thyrocytes and the FRTL5 cell line quantitatively recovered p500, confirming its identity and indicating an epithelial origin. Gel filtration of secreted thrombospondin eluted at a high molecular weight, suggesting complexation with components of the extracellular matrix. Further, immunofluorescence showed cellular codistribution of thrombospondin and thyroglobulin, although thrombospondin exhibited predominantly an extracellular, basolateral deposition. It seems likely that thrombospondin production by thyrocytes plays a role in the growth or development of the thyroid epithelium.

Animals↗

Temporal profile and significance of metabolic failure and trophic changes in the canine cerebral arteries during chronic vasospasm after subarachnoid hemorrhage.

To investigate the pathogenetic significance of metabolic failure observed in spastic cerebral arteries after subarachnoid hemorrhage (SAH), the temporal profile of alterations in the arterial content of high-energy phosphates was studied. A canine model of double hemorrhage was used. Constriction of the basilar artery was measured angiographically on Days 3, 5, 7, and 14 after SAH in separate groups of animals. Adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), guanosine triphosphate (GTP), guanosine diphosphate, creatine phosphate (CrP), and creatine (Cr) levels in the arteries were assayed using high-performance liquid chromatography. A time-dependent development of angiographic spasm was confirmed. A mild vasospasm was seen in the group studied 3 days after SAH, progressed in the Day 5 group, remained comparably severe in the Day 7 group, and resolved partially in the Day 14 group. The content of high-energy phosphates (ATP, GTP, and CrP) declined rapidly over the course of the study, and a significant reduction in ATP, GTP, and CrP was observed in the Day 3 group. Levels of ATP and CrP decreased further in the Day 5 and 7 groups. The decrement in GTP was completed in the early phase; a significant reduction took place in the Day 3 group, with no progression thereafter and no recovery through Day 14. Total adenylate (ATP + ADP + AMP) and total creatine (Cr + CrP) content diminished markedly over the course of the study. These results indicate that metabolic failure and trophic disturbance in the cerebral artery occurs with a rapid onset following SAH and progresses in close association with the development of vasospasm, suggesting a significant causal relationship with the pathogenesis.

Adenosine Triphosphate↗