Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 685 records · Page 38Linked to original sources

PubMed1998

In vivo assay of protein-protein interactions in Hin-mediated DNA inversion.

In order to form the catalytic nucleoprotein complex called the invertasome in the Hin-mediated DNA inversion reaction, interactions of the DNA-binding proteins Hin and Fis are required. Assays for these protein-protein interactions have been exploited with protein cross-linkers in vitro. In this study, an in vivo assay system that probes protein-protein interactions was developed. The formation of a DNA loop generated by protein interactions resulted in transcriptional repression of an artificially designed operon, which in turn increased the chance of survival of Escherichia coli host cells in a streptomycin-containing medium. Using this system, we were able to assay the Hin-Hin interaction that results in the pairing of the two recombination sites and protein interactions that result in the formation of the invertasome. This assay system also led us to find that an individual Hin dimer bound on a recombination site can form a stable complex with Fis bound on the recombinational enhancer; this finding has never been observed in in vitro studies. Possible pathways toward the formation of the invertasome are discussed based on the assay results for a previously reported Hin mutant.

Bacterial Proteins↗

PubMed1998

Construction of retroviral vectors with improved safety, gene expression, and versatility.

Murine leukemia virus (MLV)-based retroviral vectors are the most frequently used gene delivery vehicles. However, the current vectors are still not fully optimized for gene expression and viral titer, and many genetic and biochemical features of MLV-based vectors are poorly understood. We have previously reported that the retroviral vector MFG, where the gene of interest is expressed as a spliced mRNA, is superior in the level of gene expression with respect to other vectors compared in the study. As one approach to developing improved retroviral vectors, we have systematically performed mutational analysis of the MFG retroviral vector. We demonstrated that the entire gag coding sequence, together with the immediate upstream region, could be deleted without significantly affecting viral packaging or gene expression. To our knowledge, this region is included in all currently available retroviral vectors. In addition, almost the entire U3 region could be replaced with the heterologous human cytomegalovirus immediately-early promoter without deleterious effects. We could also insert internal ribosome entry sites (IRES) and multicloning sites into MFG without adverse effects. Based on these observations, we have constructed a series of new, improved retroviral constructs. These vectors produced viral titers comparable to MFG, expressed high levels of gene expression, and stably transferred genes to the target cells. Our vectors are more convenient to use because of the presence of multicloning sites and IRESs, and they are also more versatile because they can be readily converted to various applications. Our results have general implications regarding the design and development of improved retroviral vectors for gene therapy.

Gene Deletion↗

PubMed1998

Endogenous calcitonin gene-related peptide modulates tachycardiac but not bradycardiac baroreflex in rats.

Effects of intracisternally administered human calcitonin gene-related peptide (8-37) [hCGRP-(8-37)], an antagonist, and hCGRP, an agonist of the CGRP receptor in the rat central nervous system, on baroreflex sensitivity (BRS) were studied in conscious male rats. Each rat sequentially received intracisternally injected 0.9% saline and then hCGRP-(8-37) at doses of 1, 2.5, and 5 nmol in a volume of 10 microliters at an interval of 15 min. Five minutes after each injection, sodium nitroprusside (SNP, 10 micrograms/kg) or phenylephrine hydrochloride (PE, 2 micrograms/kg) was intravenously administered to induce reflex tachycardia or bradycardia, respectively. Intracisternally administered hCGRP-(8-37) increased BRS of the reflex tachycardia induced by SNP in a dose-related manner but did not change the BRS after PE. Intracisternally injected hCGRP significantly decreased the BRS after SNP. The lowering effect of hCGRP on BRS after SNP was inhibited by hCGRP-(8-37) injected before hCGRP. These results suggest that endogenous CGRP in the lower brain stem is selectively involved in the tachycardiac but not the bradycardiac baroreflex and modulates the baroreflex in an inhibitory rather than facilitatory fashion.

Animals↗

PubMed1998

Evaluation of renal tubular functions in convalescent phase of hemorrhagic fever with renal syndrome.

To evaluate renal tubular functions and to investigate the causative factors of urinary-concentrating defects in the late stage of hemorrhagic fever with renal syndrome (HFRS), 11 HFRS patients in the convalescent phase were studied and compared with 8 acute renal failure (ARF) patients in convalescence (disease controls) and 9 healthy adults preparing for kidney donation (normal controls, NC). Minimal urine osmolality induced by water loading was higher (p < 0.05) in HFRS (89.5 +/- 22.1 mosm/kg) and ARF patients (84.8 +/- 14.7 mosm/ kg) than in NC (47.8 +/- 4.6 mosm/kg), but the solute-free water clearance of HFRS patients (9.0 +/- 1.3%), measured at maximal diuresis, was not different from that of ARF patients (6.7 +/- 1.2%) or NC (10.5 +/- 1.4%). After 12-hour water deprivation + vasopressin stimulation, HFRS had lower urine osmolality (433.7 +/- 31.1 versus 850.0 +/- 35.1 mosm/kg; p < 0.05), urine-to-plasma osmolality ratio (1.47 +/- 0.11 versus 2.91 +/- 0.11; p < 0.05), and solute-free water reabsorption (0.53 +/- 0.07 versus 0.91 +/- 0.12%; p < 0.05) than NC. As compared with ARF patients (1.09 +/- 0.16%) or NC (1.49 +/- 0.16%), HFRS patients (0.43 +/- 0.20%) had lower solute-free water reabsorption measured at maximal antidiuresis induced by water deprivation + vasopressin stimulation + hypertonic saline infusion (p < 0.05). In HFRS, the plasma vasopressin level and plasma vasopressin/osmolality ratio increased from 3.9 +/- 0.8 to 6.1 +/- 1.1 pg/ml and from 0.013 +/- 0.003 to 0.020 +/- 0.004 pg/ml/mosm/kg after 12-hour water deprivation, respectively (p < 0.01). However, neither basal nor stimulated values of the plasma vasopressin level or plasma vasopressin/osmolality ratio was different among the 3 groups. HFRS patients were not different from ARF patients or NC in lithium clearance, urinary-acidifying capacity, and fractional excretions of sodium, potassium and bicarbonate. We conclude that in the convalescent phase of HFRS, the urinary-acidifying ability is not disturbed, the urinary-diluting defect is mild, and the urinary-concentrating capacity is obviously impaired. This study suggests that the most important factor contributing to the urinary-concentrating defect in HFRS is the reduced collecting duct responsiveness to vasopressin.

Acute Kidney Injury↗

PubMed1998

Localized in vivo 13C-NMR of glutamate metabolism in the human brain: initial results at 4 tesla.

Using optimized administration of 13C-labeled glucose, the time course of the specific activity of glucose was measured directly by in vivo 13C-NMR in the human brain at 4 Tesla. Subsequent label incorporation was measured at the C2, C3 and C4 positions of both glutamate and the well-resolved C2, C3 and C4 resonances of glutamine and at the C2 and C3 positions of aspartate. GABA was clearly observed for the first time in vivo, suggesting a substantial GABA turnover in the normal human visual cortex. Likewise, lactate C3 labeled with an estimated active pool size on the order of 0.5 mM. A model of cerebral glutamate metabolism is proposed which predicts that glutamatergic action ('neurotransmission'), pyruvate carboxylase flux, TCA cycle activity, glucose consumption and exchange across the mitochondrial membrane can be assessed simultaneously in the human brain.

Aspartic Acid↗

PubMed1998

Cardiac mitogen-activated protein kinase activities are chronically increased in stroke-prone hypertensive rats.

To examine chronic changes in mitogen-activated protein (MAP) kinases in cardiac hypertrophy, we determined the activities of two subfamilies of MAP kinases, including extracellular signal-regulated kinases (ERKs) and c-Jun NH2-terminal kinases (JNKs), in the heart of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) aged 5, 8, 14, and 24 weeks. MAP kinases were determined by using in-gel kinase assay. In both the left and right ventricles of WKY, the activities of ERKs (p44ERK and p42ERK) and JNKs (p46JNK and p55JNK) decreased significantly with age, indicating that aging remarkably downregulated cardiac MAP kinase activities. In SHRSP, left ventricular ERK and JNK activities were already significantly higher at the mild hypertensive phase than they were in the same age of WKY, and they remained higher until development of left ventricular hypertrophy. On the contrary, the right ventricle of SHRSP, which did not exhibit cardiac hypertrophy, had no significant increase in ERK or JNK activities compared with WKY, except for the slight increase in p55JNK in 24-week-old SHRSP. Antihypertensive treatment of SHRSP with imidapril, an angiotensin-converting enzyme inhibitor, decreased the left ventricular JNK activities (P<.01) but did not affect ERK activities, suggesting the contribution of hypertension or the renin-angiotensin system to the increase in JNKs. Our observations provide the first evidence that both ERK and JNK activities are higher in the left ventricle of SHRSP than WKY. However, further study is needed to elucidate the mechanism and the significance of the increased cardiac MAP kinases in SHRSP.

Aging↗

PubMed1998

Lung lymphocytes proliferate minimally in the murine pulmonary immune response to intratracheal sheep erythrocytes.

The importance of in situ lymphocyte proliferation for net accumulation of lung lymphocytes during pulmonary immune responses and in immunologic lung diseases remains uncertain. Accordingly, we studied the experimental pulmonary immune response of antigen-primed C57BL/6 mice to intratracheal challenge with the particulate antigen sheep red blood cells. Uptake of nucleotide analogs (bromodeoxyuridine in vivo and tritiated thymidine in vitro), expression of the cell activation antigens CD25 and CD69 by flow cytometry, and response to the antimitotic agent hydroxyurea (in vivo) were measured. Although many lung lymphocytes and CD4+ T cells were CD25+ and CD69+, indicating recent activation, all techniques demonstrated that lung lymphocytes proliferated minimally in vivo. Blockade of cell division by hydroxyurea administration for 24 h did not significantly decrease lung lymphocyte accumulation on Day 3 after challenge. Lung lymphocytes also proliferated minimally in vitro (even on macrophage removal and despite addition of exogenous interleukin [IL]-2 or IL-4). However, lung lymphocytes responded vigorously to mitogens (immobilized anti-CD3, phytohemagglutinin, or concanavalin A), excluding global unresponsiveness to restimulation. Thus, in this model of pulmonary immunity, accumulation of lung lymphocytes does not require local T-cell proliferation and presumably depends instead on recruitment.

Animals↗

PubMed1998

Testing the influence of the health belief model and a television program on nutrition behavior.

This study proposed to identify relevant factors of the health belief model (HBM) that provide motivation for people to engage in healthy dietary behavior. The impact of a TV program was also assessed using a longitudinal study with 300 participants and measuring the influence of path coefficients in the HBM that predicted salience, motivation, and healthy eating practices. Findings suggested that nutrition behavior was influenced by susceptibility and efficacy mediated through health motivation and salience. Program viewing boosted salience regardless of age, education, or household size by significantly increasing viewers' confidence in their nutrition knowledge base.

Journal Article↗

PubMed1998

Further characterization of thyroid hormone response elements in the human type 1 iodothyronine deiodinase gene.

The increased type 1 iodothyronine deiodinase expression in hyperthyroid patients increases the fraction of plasma T3 generated from T4 by the propylthiouracil-sensitive pathway. In this study, we extend our analysis of the thyroid hormone response elements (TREs) in the 5' flanking region of the human dio1 gene. The 5' TRE (TRE2), a direct repeat separated by 4 bp (DR+4) at -660 bp, arises from an A to G substitution in an Alu sequence, the first example of this phenomenon. An SP1 binding site immediately 5' to TRE2 increases basal expression of a 430-bp dio1 promoter-chloramphenicol acetyltransferase construct in the presence of unliganded thyroid hormone receptor, thus decreasing T3 responsiveness, but does not do so when this complex is placed in its more 5' wild-type location. The two octameric binding sites of TRE1, a retinoid X-receptor independent DR+10 structure at -90, can be exchanged or inverted without loss of T3 response potency, despite significant changes in thyroid hormone receptor binding, as assessed by gel shift assays. However, the retinoic acid response of the 716-bp dio1 5' flanking region is unaffected by elimination of TRE2 but is lost with mutations in TRE1. These findings indicate the importance of functional analyses of potential ligand-responsive transcription factors, as well as the influence of position, on TRE function and interaction with basal transcription factors. The unusual features of these TREs emphasize the need to consider alternatives to canonical half-site arrangements of receptor binding sites and contexts in the evaluation of T3- and retinoic acid-responsive genes.

Base Sequence↗

PubMed1998

Doppler echocardiographic assessment and cardiac gene expression analysis of the left ventricle in myocardial infarcted rats.

The purpose of this study was to examine cardiac geometry and function by Doppler echocardiography and to analyze mRNA expression of cardiac phenotype and extracellular matrix in myocardial infarcted rats. Doppler echocardiograms and hemodynamics were measured 2 weeks after myocardial infarction (MI). mRNA levels in the non-infarcted left ventricle (LV) and infarct site were measured by Northern blot analysis. LV internal diastolic dimension was greater in infarcted (MI) than in sham-operated rats (control) (MI 7.2+/-0.3 mm vs control 4.6+0.3 mm, p<0.01). The fractional shortening decreased in MI rats (MI 32+4% vs control 61+/-3%, p<0.01). Peak early filling velocity increased in MI rats (MI 91+/-5 cm/sec vs control 72+/-4 cm/sec, p<0.05), and deceleration rate of the early filling wave was more rapid in rats with MI (MI 25.1+/-2.8 m/sec2 vs control 12.4+/-1.7 m/sec2, p < 0.01). Late filling velocity decreased (MI 16+/-3 cm/sec vs control 35+/-6 cm/sec, p <0.05), resulting in a marked increase in the ratio of early filling to late filling (MI 7.1+/-1.2 vs control 2.5+/-0.4, p<0.01). mRNA levels for beta-myosin heavy chain (beta-MHC), a-skeletal actin, atrial natriuretic polypeptide (ANP), collagen types I and III, and matrix metalloproteinase 2 (MMP-2) in the non-infarcted LV increased significantly by 1.8-, 2.4-, 4.7-, 2.6-, 2.1- (all p<0.01) and 1.4-fold (p<0.05), respectively, compared with sham-operated myocardium. In the infarct site, mRNA levels for transforming growth factor (TGF)-beta1, collagen types I and III, and MMP-2 significantly increased by 3.2-, 11.0-, 9.7-, and 6.3-fold (all p<0.01), respectively, compared with sham-operated myocardium. Myocardial infarcted rat was characterized by cavity dilation and marked abnormalities of systolic and diastolic function, accompanied by a shift of myocytes to fetal phenotype and activation of collagen genes in the non-infarcted myocardium.

Actins↗

PubMed1998

Effect of manidipine hydrochloride, a calcium antagonist, on isoproterenol-induced left ventricular hypertrophy.

We examined the effect of a calcium antagonist, manidipine hydrochloride, on cardiac hypertrophy and the expression of the atrial natriuretic peptide (ANP), transforming growth factor beta 1 (TGF-beta 1), and extracellular matrix protein genes in rats with isoproterenol-induced cardiac hypertrophy. Rats were continuously infused with saline or isoproterenol (0.5 mg/kg per day) for 7 days using an osmotic minipump. Treatment with manidipine hydrochloride (once a day at 3 mg/kg) began 1 day before minipump implantation and continued until the end of the experiments (each group; n = 6). After treatment, left ventricular weight was measured and mRNA was extracted and analyzed by Northern blot hybridization. Isoproterenol increased left ventricular weight (2.40 +/- 0.04 g/kg; p < 0.01) without increasing blood pressure. ANP, collagen type I and type III, and fibronectin mRNAs were increased 1.5-(p < 0.01), 1.9- (p < 0.01), 2.7- (p < 0.01), and 3.2-fold (p < 0.01), respectively, by isoproterenol infusion. However, TGF-beta 1, collagen type IV, and laminin B1 and B2 mRNA levels were unchanged by isoproterenol. Manidipine hydrochloride prevented isoproterenol-induced left ventricular hypertrophy (2.26 +/- 0.02 g/kg; p < 0.01) and expression of mRNA of ANP (0.9-fold of the control value; p < 0.01), collagen types I (1.1-fold; p < 0.01) and type III (1.6-fold; p < 0.01), and fibronectin (1.1-fold; p < 0.01). Thus, manidipine hydrochloride prevented cardiac hypertrophy and changes in the expression of genes for ANP and interstitial components of extracellular matrix induced by isoproterenol.

Animals↗

PubMed1998

Renal endothelin in FK506-induced nephrotoxicity in spontaneously hypertensive rats.

FK506, a major immunosuppressive agent, often causes nephrotoxicity accompanied by renal vasoconstriction. It is recognized that endothelin (ET) plays a role in the cyclosporin A-induced nephrotoxicity, but the involvement of ET in the FK506-induced renal dysfunction is still poorly understood. We elicited nephrotoxicity by daily administration of FK506 in spontaneously hypertensive rats, and we examined the renal gene expression of ET and its receptors and the effects of an ET receptor antagonist on FK506-induced renal dysfunction. FK506 administration (4 mg/kg/day, i.m.) for 14 days induced nephrotoxicity, including a renal vasoconstriction and a decrease in glomerular filtration rate. The renal dysfunction was accompanied by an increase in ET-1 mRNA levels, while ET(B)-receptor mRNA was unaffected. Continuous administration of an ET(A)/ET(B) antagonist, TAK-044 (3 mg/day, s.c.), which effectively blocked systemic and renal vascular responses to exogenously administered ET-1, partially attenuated the FK506-induced renal vasoconstriction. However the reduced glomerular filtration rate were not affected by TAK-044. Thus, although enhanced gene expression of ET-1 in the kidney is involved in the renal vasoconstriction, ET does not play a major role in the FK506-induced renal dysfunction.

Animals↗

PubMed1998

Angiotensin II type 1-receptor antagonist candesartan cilexitil prevents left ventricular dysfunction in myocardial infarcted rats.

The purpose of this study was to analyze the effect of the angiotensin II type 1-receptor antagonist candesartan cilexitil on left ventricular systolic and diastolic function and mRNA expression of contractile proteins, collagen, and Ca2+ handling protein in myocardial-infarcted rats. After myocardial infarction, the animals were randomly assigned to candesartan cilexitil-treated or untreated groups (MI). We performed Doppler-echocardiographic examination and measured the hemodynamics at four and twelve weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed. At four weeks in MI, left ventricular end-diastolic dimension increased (Control, 6.2+/-0.6 mm; MI, 8.7+/-0.6 mm; P < 0.01), fractional shortening decreased (Control, 41+/-5%; MI, 16+/-3%; P < 0.01) and E wave deceleration rate increased (Control, 14.3+/-2.0 m/sec2; MI, 23.3+/-2.3 m/sec2; P < 0.01). Candesartan cilexitil significantly prevented these changes. The mRNA expressions of beta-myosin heavy chain, alpha-skeletal actin, atrial natriuretic peptide, and collagens I and III in the non-infarcted left ventricle and right ventricle were increased at four weeks and were significantly suppressed by treatment with candesartan cilexitil. At four weeks, Na+-Ca2+ exchanger mRNA expression was increased, and candesartan cilexitil suppressed this increase. At twelve weeks, sarcoplasmic reticulum Ca2+-ATPase mRNA expression in the infarcted region including the adjacent non-infarcted left ventricle and right ventricle were decreased and candesartan cilexitil restored it to the control level. Candesartan cilexitil prevented the systolic and diastolic dysfunction and abnormal cardiac mRNA expression in myocardial-infarcted rats.

Angiotensin Receptor Antagonists↗

PubMed1998

Assessment of cardiac function and gene expression at an early phase after myocardial infarction.

The purpose of this study was to examine left ventricular function and cardiac gene expressions at an acute phase after myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Two days after MI, we performed Doppler-echocardiography and measured the systolic and diastolic function. We then analyzed the contractile protein and extracellular matrix mRNAs of cardiac tissues in the infarcted region, including the adjacent noninfarcted myocardium (the adjacent noninfarcted myocardium) and the remote noninfarcted myocardium, by Northern blot hybridization. Fractional shortening decreased significantly to 28%. Peak early diastolic filling wave (E wave) velocity increased in MI rats (MI; 90 +/- 3 cm/s versus the control; 71 +/- 2 cm/s, p < 0.05), and the deceleration rate of the E wave velocity was more rapid in MI rats (MI; 22.0 +/- 2.6 m/s2 versus the control; 16.5 +/- 2.0 m/s2, p < 0.01). Atrial filling wave (A wave) velocity decreased, resulting in a marked increase in the ratio of E wave to A wave velocity (MI; 3.1 +/- 0.3 versus the control; 2.1 +/- 0.2, p < 0.01). In the adjacent noninfarcted myocardium, mRNA levels for alpha-skeletal actin, atrial natriuretic polypeptide (ANP), transforming growth factor-beta 1(TGF-beta 1), fibronectin, and collagen types I and III increased significantly. In the remote noninfarcted myocardium, mRNA levels for alpha-skeletal actin, ANP, and collagen types I and III increased, while mRNA levels for beta-myosin heavy chain, TGF-beta 1 and fibronectin did not change. We observed left ventricular dysfunction and different gene expression between adjacent noninfarcted myocardium and in the remote noninfarcted myocardium two days after MI. These findings suggest that cardiac gene expression after MI may be a compensation reaction for cardiac dysfunction induced by myocardial damage.

Animals↗

PubMed1998

Activation of glomerular mitogen-activated protein kinases in angiotensin II-mediated hypertension.

The in vivo signal transduction pathway, responsible for hypertension-induced glomerular injury, remains to be clarified. In this study, the effect of angiotensin II (Ang II)-induced hypertension was examined on glomerular mitogen activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK), and on glomerular transcription factors activator protein-1 (AP-1) and Sp 1. MAPK activities were determined by in-gel kinase assay. DNA binding activity of AP-1 and Sp 1 was determined by gel mobility shift assay. Continuous infusion of Ang II (1000 ng/kg per min, intravenously) to conscious rats rapidly increased BP, followed by the rapid and transient activation of glomerular p42 and p44 ERK and p46 and p55 JNK with the peak at 15 to 180 min. Glomerular AP-1 binding activity was increased 2.6-fold (P < 0.01) at 24 h after the start of Ang II infusion. Supershift analysis showed that the activated AP-1 complexes contained c-Fos and c-Jun proteins. On the other hand, glomerular Sp 1 DNA binding activity was not changed throughout 7 d of Ang II infusion. These results provided the first in vivo evidence that Ang II-induced hypertension causes the activation of glomerular ERK and JNK, leading to the activation of AP-1. Thus, ERK and JNK signaling cascades, via the activation of AP-1, may be implicated in the development of hypertension-induced glomerular injury.

Angiotensin II↗

PubMed1998

Effects of prednisolone on glomerular signal transduction cascades in experimental glomerulonephritis.

In vitro data support that activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) regulate the gene expression of numerous growth factors and cytokines involved in the development of glomerulonephritis (GN). However, the in vivo activation and role of these transcription factors are poorly understood. This study examines whether these transcription factors are activated in antithymocyte serum (ATS)-induced GN in vivo and whether prednisolone suppresses activation of them. As assessed by gel mobility shift assay, glomerular DNA binding activity of AP-1 containing both c-Jun and c-Fos and NF-kappaB composed of P-50 and P-65 subunits was significantly increased after ATS injection. Furthermore, as estimated by in-gel kinase assay, glomerular activity of extracellular signal-regulated kinases (ERK) and c-jun NH2-terminal kinases (JNK), which are mitogen-activated protein kinases (MAPK) known to activate AP-1 and NF-kappaB in vitro, was significantly increased after ATS injection, preceding the increase in AP-1 activity. Prednisolone treatment significantly prevented the increase in urinary protein and albumin excretion and glomerular cell proliferation in ATS-induced GN, indicating the beneficial effects of prednisolone on this GN. Prednisolone significantly suppressed the increased glomerular ERK and JNK activities and AP-1 binding activity, but not glomerular NF-kappa binding activity. This study provides the first evidence of the marked increase in glomerular MAPK activities, and AP-1 and NF-kappa binding activities in ATS-induced GN. The beneficial effect of prednisolone on this GN may be partially mediated by the suppression of MAPK, followed by the suppression of AP-1.

Animals↗

PubMed1998

Algorithms for resource allocation of substance abuse prevention funds based on composite risk-factor index score: a case study on state of Florida--Part 2.

The purpose of Part 2 is to develop a model for resource allocation of state prevention funds to be distributed to its substate jurisdictions based on the relative need for prevention services measured in terms of composite risk-factor index (COMRISK) scores computed for each county. The risk factors are extracted from an extensive review of risk and protective factors addressed in the prevention literature. Based on twenty-two risk and protective factors identified, we were able to explain 71.3 percent of the total variation in student drug using behavior observed at the individual level. By aggregating individual COMRISK scores to the county level, we were able to determine aggregated COMRISK index scores at the county level. By determining the proportion of each county's share of the total statewide COMRISK and by weighting the latter proportion by the population size of each county, we have devised Prevention Needs Index (PNI) score based on the risks for each county. Finally, the county's share of PNI score as a proportion of the total statewide PNI score is computed. The latter proportion is then multiplied by the total amount of prevention resources available at the state. In this way, we were able to develop an alternative resource allocation model solely based on risk and protective factors for determining prevention needs of each county, independent of composite index score of drug use (COMDRUG) presented in Part 1. A comparison of three models for resource allocation has shown a significant amount of similarity of the total funds computed for each county. Accordingly, no preference is made among the resource allocation models suggested, although it is emphasized that the final decision concerning the level of funding must be made on the selection of the resource allocation algorithms rather than the suggested amount of funding computed for each county.

Adolescent↗

PubMed1998

Toward a new paradigm in substance abuse and other problem behavior prevention for youth: youth development and empowerment approach.

The purpose of this article is to 1) address a paradigm shift taking place in the field of substance abuse prevention directed for youth and 2) to introduce an innovative approach to substance abuse and other problem behavior prevention that reflects this shift in prevention paradigm. The new path introduced is youth development and empowerment (YD&E) approach. In order to establish a conceptual foundation for this approach, this article 3) reviews the theoretical advances made in the field of substance abuse prevention during the last three decades. This is followed by a conceptualization of the processes of implementing the YD&E program by 4) specifying the mechanism used for the empowering processes and by 5) identifying the structural components of the youth empowerment model that serve the empowering processes. It is hoped that this article serves as a conduit for an improved approach to adolescent substance abuse prevention and youth development that goes beyond, rather than against, the traditional risk-factor approach. In this new approach, youths are viewed as assets and resources to our community rather than social problems or community liabilities. The organizing concept of this new paradigm is: social, economic, and public opportunity denied to youth is equal to social problems imposed on youth by adults.

Adolescent↗