Biomedical subjects

C Shin

Publications and source records attributed to C Shin.

At least 37 records · Page 2Linked to original sources

PubMed2000

Immunohistochemical study on the distribution of the voltage-gated calcium channel alpha(1B) subunit in the mature rat brain.

Many neuronal processes are regulated by calcium influx through voltage-gated calcium channels. Among these calcium channels, the N-type channel has been shown to play a significant role in the regulation of neurotransmitter release. This present report has demonstrated the distribution of the alpha(1B) subunit of the N-type calcium channel in the mature rat brain. The most striking findings were the highest immunoreactivity in the CA1 region of the hippocampus and the clear demarcation in the thalamus. Characteristic patterns of distribution were noted in the cerebral cortex, hippocampus, caudate-putamen, thalamus, and cerebellum. In the cerebral cortex, strong staining was seen in layers II-III and V. In the basal ganglia, the staining intensity was high in the caudate-putamen, whereas there was no immunoreactivity in the globus pallidus. Although the staining intensity was relatively low compared to that of the forebrain, moderate alpha(1B)-IR was found in the dorsal cochlear nucleus and mesencephalic trigeminal nucleus. The detailed features of this study will extend our current knowledge of alpha(1B) subunit distribution in terms of the number of neuroanatomical areas examined, by investigating alpha(1B) subunit protein expression, for the first time.

Animals↗

PubMed2000

Immunohistochemical study on the distribution of neuronal voltage-gated calcium channels in the rat cerebellum.

Many neuronal processes are regulated by calcium influx through voltage-gated calcium channels (VGCCs), including protein phosphorylation, gene expression, neurotransmitter release, and firing patterns of action potential. In the present study, we have used anti-peptide antibodies directed against a unique sequence in rat alpha(1A), alpha(1B), alpha(1C) and alpha(1D) subunits of VGCCs to determine their cellular distribution in normal rat cerebellum. Throughout the molecular layer, immunoreactivity for alpha(1B) and alpha(1D) subunits were found in the cell bodies of basket and stellate cells as well as in the neuropil. In the Purkinje cells, only alpha(1C)-IR was observed in the dendritic branches of Purkinje cells, whereas immunoreactivity for alpha(1B) and alpha(1D) subunits were rarely found in the cell bodies of Purkinje cells. Immunoreactivity for the alpha(1A), alpha(1B,) and alpha(1D) subunits were strong in the granule cell bodies, whereas alpha(1C)-IR was not prominent in the cell bodies. In the cerebellar nuclei, a distinct band of punctate immunoreactivity for the alpha(1A), alpha(1B), alpha(1C), and alpha(1D) subunits were observed. The overall results of the above localization study showed clearly that the alpha(1A), alpha(1B,) alpha(1C) and alpha(1D) pore forming subunits of VGCCs have differential distribution in the rat cerebellum. The present studies may provide useful data for such future investigations to understand the role of calcium channels in neurological pathways.

Animals↗

PubMed2000

Region-specific changes of NOS-IR cells in the basal ganglia of the aged rat.

Nitric oxide (NO) is a free radical postulated to act as a neurotransmitter, neuromodulator, or second messenger molecule in the central nervous system. Several findings suggest that NO production may be decreased in the aged rats. In the present study, we investigated regional discrepancies in changes with aging in the number of nitric oxide synthase-immunoreactive (NOS-IR) cells in the basal ganglia of the aged rat by immunocytochemistry. The number of NOS-IR neurons in the striatum and substantia innominata of the aged rat decreased. In contrast, the number of NOS-IR neurons in the subthalamic nucleus increased in the aged rat. On the other hand, the number of NOS-IR neurons in the nucleus accumbens and olfactory tubercle did not change. Taken together, important functional changes can be caused by the region-specific changes of NOS-IR neurons in the basal ganglia with aging.

Aging↗

PubMed2000

Reducing adolescents' aggressive and hostile behaviors: randomized trial effects of a brief family intervention 4 years past baseline.

OBJECTIVE: To examine the long-term effects of a brief family intervention on aggressive and hostile behaviors of adolescents in the general population. DESIGN: Randomized trial including 22 public schools assigned to the Iowa Strengthening Families Program or a control condition. Analyses supported sample representativeness and failed to show differential attrition effects 4 years after baseline. INTERVENTION: Seven-session intervention for parents and their sixth-grade children. MEASURES: The multi-informant, multimethod measures included independent observer ratings of adolescent aggressive and hostile behaviors in adolescent-parent interactions, family-member report of aggressive and hostile behaviors in those interactions, and adolescent self-report of aggressive and destructive conduct across settings. Data were collected during the 6th (preintervention and postintervention), 7th, 8th, and 10th grades. RESULTS: All measures showed a generally positive trend in intervention-control group differences over time. During 10th grade, significant intervention-control differences were found for adolescent self-report of aggressive and destructive conduct (P =. 01), with relative reduction rates ranging from 31.7% to 77.0%. Significant differences were shown for observer-rated aggressive and hostile behaviors in adolescent-parent interactions (P =.01); differences in family member reports of those behaviors were not significant. Supplemental analyses of both interactional behavior measures, specific to parent sex, indicated significant experimental group differences in interactions with mothers (P =.04 for both measures) but not with fathers. CONCLUSIONS: Brief family competency-training interventions designed for general populations can reduce aggressive and hostile behaviors in adolescents' interactions with parents and adolescent aggressive behaviors outside of the home setting. Thus, this type of intervention has important public health implications. Arch Pediatr Adolesc Med. 2000;154:1248-1257.

Adolescent↗

PubMed2000

Synergistic combinatorial stroke therapy: A quantal bioassay of a GABA agonist and a glutamate antagonist.

We sought to prolong the window for stroke treatment using synergistic combinatorial therapy. We used the intraluminal filament occlusion model in rats to cause focal cerebral ischemia and a quantal bioassay to measure efficacy. The GABA agonist muscimol and the glutamate antagonist MK-801 were used alone and in combination at various times after ischemia onset. At progressively longer treatment delay intervals (30, 60, 75, 120, 240, and 360 min), higher doses of the single drugs were required to achieve neuroprotection. In contrast, the combination 1.0 mg/kg muscimol plus 0.5 mg/kg MK-801 was effective at all delay intervals studied except the longest (P < 0.05 at each time). After 240 min from ischemia onset, the combination was more effective than either single agent (P < 0.05 for each drug dose), suggesting synergism. The neuroprotective effect could not be demonstrated using morphometry. The treatment effects were probably not due to hypothermia because brain temperatures recorded in awake, unregulated subjects remained normo- or slightly hyperthermic following all treatments. Awake subjects kept on a heating pad exhibited mild brain hyperthermia. The combination caused a drop and MK-801 caused a significant increase in mean arterial blood pressure (main effects F(5,172) = 29, P < 0.0001). The combination of a GABA agonist and glutamate antagonist appears to possess synergistic neuroprotective effects when treatment is delayed up to 240 min following the onset of cerebral ischemia. Temperature regulation causes hyperthermia in awake subjects. The quantal bioassay is one method suitable for studies of synergistic stroke therapy.

Animals↗

PubMed2000

Modeling factors influencing enrollment in family-focused preventive intervention research.

The reported study tests an extension of a previously supported model of family context and health belief predictors of parental inclination to enroll in preventive interventions. The extended model addresses limitations in the prior investigation; it examines the role of intervention-related beliefs and inclinations on actual enrollment in a skills training intervention research project. Model testing was conducted with a sample of 635 parents of 6th graders who completed a prospective participation factor survey and were recruited for an intervention research project 6 months later. The model fit was strong and all but one of the primary hypothesized effects were supported. Notably, both stated inclination to enroll in an intervention and in the research project had significant positive effects on actual project enrollment occurring 6 months later. Perceived intervention benefits and barriers had significant effects on both types of stated inclination to enroll. Examination of modification indices for the model suggested an additional path linking educational attainment with actual enrollment.

Adult↗

PubMed2000

Neurophysiologic basis of functional neuroimaging: animal studies.

Functional neuroimaging adds metabolic or biochemical information to that obtained with anatomic imaging, allowing localization of a neural function. Positron emission tomography and single photon emission tomography make use of radioactive tracers tagged to a molecule which can indicate glucose metabolism, oxygen consumption, or blood flow. Functional magnetic resonance imaging uses the different magnetic properties of oxyhemoglobin and deoxyhemoglobin to identify areas of increased blood flow, which, in turn, reflects neuronal activation. Magnetic resonance spectroscopic imaging, with magnetically labeled molecules, can be used to follow biochemical pathways. Functional neuroimaging is based on the experimental data that neuronal activation leads to increased metabolism. Uptake of glucose and oxygen increases to meet increased energy needs. The fractionally increased glucose appears to be taken up mostly by glia, which metabolize it through glycolysis. The end product, lactate, is released for neuronal uptake and subsequent oxidative phosphorylation. To meet these metabolic needs, blood flow increases to such an extent that overall capillary oxyhemoglobin concentration increases. This changes the magnetic signal in the region and permits functional magnetic resonance imaging studies. Recent data suggest that there is an initial decrease in the concentration of oxyhemoglobin which may be more spatially specific to the area of neuronal activation. Further refinements in functional neuroimaging will lead to improved understanding of the normal functional anatomy of the brain and will shed further light on the pathophysiology of many neurologic disorders.

Animals↗

PubMed2000

Effect of ganaxolone in a rodent model of cerebral hematoma.

BACKGROUND AND PURPOSE: Therapy with gamma-aminobutyric acid (GABA) agonists appears to improve outcome after experimental hematoma but with unacceptable side effects. We looked to synthetic GABA agonists, or positive GABA modulators, widely developed as anticonvulsants and anxiolytics, to find compounds that may be effective. Ganaxolone is a synthetic neuroactive steroid that positively modulates GABA. We sought to determine whether ganaxolone was beneficial using a model of intracerebral hematoma. METHODS: We stereotaxically injected varying doses of bacterial collagenase into the caudate nucleus of rats to induce blood-brain barrier failure and hematoma formation. Four hours later, we administered intravenously 15 or 30 mg/kg ganaxolone (n=23 each group), 20 mg/kg pregnanolone (n=21), or vehicle (n=30). Forty-eight hours after collagenase injection, we rated each animal using a standard rodent neurological examination. The ratings were compared with the amounts of injected collagenase using the quantal bioassay procedure. Other sets of animals were tested later for visuospatial learning. Brains were then prepared for histomorphometry, and brain volumes were estimated. RESULTS: We found that ganaxolone 30 mg/kg significantly increased the ED(50) in the bioassay, for a potency ratio of 1.8+/-0.41 compared with vehicle (P<0.05). Ganaxolone 15 mg/kg and pregnanolone did not affect neurological outcome. Ganaxolone 30 mg/kg did not clearly improve visuospatial learning several weeks after hemorrhage. Ganaxolone exhibited a weak effect on cerebral volumes 48 hours after stroke, but 3 months after hemorrhage no such effect could be detected. CONCLUSIONS: Ganaxolone improves neurological outcome 48 hours after intracerebral hematoma but not visuospatial learning several weeks after intracerebral hematoma. Histological evidence of damage was reduced at 48 hours but not at 3 months.

Animals↗

PubMed1999

Reactive astrocytes express p53 in the spinal cord of transgenic mice expressing a human Cu/Zn SOD mutation.

In a previous study, we reported increased NOS expression in the astrocytes in the spinal cord of SOD mutant transgenic mice that are used as ALS animal model. Recently, Messmer and Brune suggested that nitric oxide-induced apoptosis is intimately related with p53-dependent signaling pathway, and de la Monte et al. reported increased p53-immunoreactivity in the spinal cord of ALS patients. In the present study, we performed immunocytochemical studies to investigate the changes of p53-immunoreactivity in the brains of the mutant transgenic mice expressing a human Cu/Zn SOD mutation. Immunocytochemistry showed intensely stained p53-IR glial cells with the appearance of astrocytes in all levels of the spinal cord of the mutant transgenic mice, but no p53-IR glial cells were observed in the spinal cord of the control mice. P53-IR astrocytes were also detected in the brain stem of the mutant transgenic mice. In the medulla, they were observed in the medullary reticular formation, hypoglossal nucleus, vestibular nucleus, dorsal motor nucleus of the vagus and nucleus ambiguus. In the pons, their presences were noted in the pontine reticular formation, and trigeminal and facial nuclei. In the midbrain, astrocytes were detected in the mesencephalic reticular formation, red nucleus and periaqueductal gray matter. In the cerebellum, intensely stained p53-IR astrocytes were detected in the intracerebellar nuclei. In contrast to the mutant transgenic mice, no p53-IR astrocytes were detected in the brain stem and spinal cord of the control mice. Further multidisciplinary investigations involving p53-mediated cellular damage and pathogenesis of ALS are needed to clarify the importance of these results.

Animals↗

PubMed1999

Assessing a public health approach to delay onset and progression of adolescent substance use: latent transition and log-linear analyses of longitudinal family preventive intervention outcomes.

This study examined the effects of the Iowa Strengthening Families Program (ISFP) and the Preparing for the Drug-Free Years program (PDFY) on young adolescent transitions from nonuse of substances to initiation and progression of substance use. Analyses incorporated 3 waves of data collected over a 2.5-year period from 329 rural young adolescents. Outcomes were analyzed by using log-linear models that incorporated substance use status frequencies derived from latent transition analyses. Effects on delayed substance use initiation were shown for both the ISFP and the PDFY at a 2-year follow-up. Also at this follow-up, the PDFY showed effects on delayed progression of use among those previously reporting initiation.

Adolescent↗

PubMed1999

Modeling long-term parent outcomes of two universal family-focused preventive interventions: one-year follow-up results.

The present investigation extended prior work by R. Spoth, C. Redmond, and C. Shin (1998). These researchers reported findings that 2 universal family-focused preventive intervention programs each had direct effects on a proximal parenting outcome (intervention-targeted parenting behaviors) and indirect effects on 2 global and distal outcomes (parent-child affective quality and general child management) at posttesting. A replication of the previously tested parenting outcome model was conducted with 1-year follow-up data and procedures identical to those used in the earlier study. Results of the present study (N = 404 families) indicate that statistically significant effects on parenting outcomes were sustained through a 1-year period following the posttest.

Adolescent↗

PubMed1999

Assessment of functional MR imaging in neurosurgical planning.

BACKGROUND AND PURPOSE: Presurgical sensorimotor mapping with functional MR imaging is gaining acceptance in clinical practice; however, to our knowledge, its therapeutic efficacy has not been assessed in a sizable group of patients. Our goal was to identify how preoperative sensorimotor functional studies were used to guide the treatment of neuro-oncologic and epilepsy surgery patients. METHODS: We retrospectively reviewed the medical records of 46 patients who had undergone preoperative sensorimotor functional MR imaging to document how often and in what ways the imaging studies had influenced their management. Clinical management decisions were grouped into three categories: for assessing the feasibility of surgical resection, for surgical planning, and for selecting patients for invasive functional mapping procedures. RESULTS: Functional MR imaging studies successfully identified the functional central sulcus ipsilateral to the abnormality in 32 of the 46 patients, and these 32 patients are the focus of this report. In epilepsy surgery candidates, the functional MR imaging results were used to determine in part the feasibility of a proposed surgical resection in 70% of patients, to aid in surgical planning in 43%, and to select patients for invasive surgical functional mapping in 52%. In tumor patients, the functional MR imaging results were used to determine in part the feasibility of surgical resection in 55%, to aid in surgical planning in 22%, and to select patients for invasive surgical functional mapping in 78%. Overall, functional MR imaging studies were used in one or more of the three clinical decision-making categories in 89% of tumor patients and 91% of epilepsy surgery patients. CONCLUSION: Preoperative functional MR imaging is useful to clinicians at three key stages in the preoperative clinical management paradigm of a substantial percentage of patients who are being considered for resective tumor or epilepsy surgery.

Adolescent↗

PubMed1998

Effect of cutaneous burn injury and resuscitation on the cerebral circulation in an ovine model.

The aim of our study was to evaluate the effects of a large cutaneous burn injury on the cerebral circulation. Anesthetized sheep (n = 8) were prepared with vascular catheters, a urinary catheter and a Richmond bolt for intracranial pressure monitoring. A scald injury was inflicted on 70 percent of total body surface area with hot water. Resuscitation was started 30 min after scald with Ringer's lactate to restore and maintain baseline oxygen delivery. Resuscitation maintained blood pressure, cardiac output and urine output at normal levels. Brain blood flow was measured with colored microspheres. During resuscitation intracranial pressure rose slowly from 10.6 +/- 1.5 to 17.0 +/- 4.0 mmHg (P < 0.05) and cerebral perfusion pressure was reduced from 86.4 +/- 6.8 to 64.1 +/- 2.8 mmHg (P < 0.05). During early resuscitation cerebrovascular resistance declined to maintain brain blood flow and oxygen delivery at baseline or better. After 6 h, mean cerebrovascular resistance was inappropriately increased during a period of reduced cerebral perfusion pressure which resulted in brain blood flow reductions of half the baseline levels. These data suggest that autoregulation maintains brain blood flow immediately after burn shock and early resuscitation, but the autoregulation may be less effective as burn resuscitation proceeds.

Animals↗

PubMed1998

Direct and indirect latent-variable parenting outcomes of two universal family-focused preventive interventions: extending a public health-oriented research base.

Recent literature underscores the need for studies of family-based preventive interventions oriented toward public health objectives. This article illustrates a program evaluation approach for the study of family intervention outcomes in general populations. Thirty-three rural schools were randomly assigned to 1 of 3 conditions: the Preparing for the Drug-Free Years Program (PDFY), the Iowa Strengthening Families Program (ISFP), and a minimal-contact control group. Self-report and observational data collected from 523 families were used to develop measurement models of 3 latent parenting constructs that included measurement method effects. Analyses were conducted to ensure initial and attrition-related group equivalencies and to assess school effects. Structural equation models of the hypothesized sequence of direct and indirect effects for both PDFY and ISFP were then fit to the data. All hypothesized effects were significant for both interventions. The discussion addresses the potential public health benefits of evaluation research on universal preventive interventions.

Adolescent↗

PubMed1998

Risk moderation of parent and child outcomes in a preventive intervention: a test and replication.

Family risk-related variations in proximal parent and young adolescent outcomes of a universal family-focused preventive intervention were examined using a cumulative index of risk incorporating sociodemographic characteristics and social-emotional adjustment measures. Results of an initial investigation involving 209 families of young adolescents suggested that intervention efficacy was largely unrelated to cumulative family risk. These findings were replicated with a second sample of 428 families. Implications for future intervention applications and outcome research are discussed.

Adolescent↗

PubMed1998

Genomic structure and sequence analysis of human HOXA-9.

In order to understand the regulatory mechanisms establishing and maintaining HOXA-9 gene expression, structural information about the gene is a prerequisite. Therefore, we sequenced the 7.2-kb region of the human HOXA-9 gene and mapped the positions of two partial cDNAs consisting of one of two 5' exons, AB (358 bp) or CD (568 bp), and a common 3' exon (exon II), which are separated by 5.4- and 1.0-kb introns, respectively. When the amino acid sequence homologies were compared with those of other Hox genes belonging to the same paralogous group, exon CD exhibited the strongest homology: 73% of 91 aa residues exactly matched those of chicken Hoxa-9. An intermediate exon (90 bp) was detected within exon CD. It was surrounded by a splice acceptor and a donor at both the 5' and 3' ends, and one branchpoint site was found near the splice-acceptor site. Nucleotide sequence analysis along this region revealed two TATA boxes, one CAAT box, one GC box, and one each of the following binding sites--engrailed, eve-stripe2-hb3, and Krox20--just upstream of exon CD. A CpG island and two RARE repeats were detected within intron I. Northern blot analysis showed that at least four main transcripts were generated along this region: all fetal tissues tested (brain, lung, liver, and kidney) produced a 1.8-kb homeobox-containing transcript (HA-9A); a 2.2- and a 3.3-kb transcript were generated from exon CD and exon II (HA-9B), especially in fetal and adult kidneys as well as in adult skeletal muscle; the 1.0-kb transcript was likely to be generated by the intermediate exon in all adult and fetal tissues. Several weak bands without tissue specificity were likely to be contributed by the hybrid transcripts between HOXA-9 and the other HOXA gene(s). Together, these results may account for the unique degree of conservation of the HOX cluster in general.

Adult↗

PubMed1997

Occupational injury and illness in the United States. Estimates of costs, morbidity, and mortality.

OBJECTIVE: To estimate the annual incidence, the mortality and the direct and indirect costs associated with occupational injuries and illnesses in the United States in 1992. DESIGN: Aggregation and analysis of national and large regional data sets collected by the Bureau of Labor Statistics, the National Council on Compensation Insurance, the National Center for Health Statistics, the Health Care Financing Administration, and other governmental bureaus and private firms. METHODS: To assess incidence of and mortality from occupational injuries and illnesses, we reviewed data from national surveys and applied an attributable risk proportion method. To assess costs, we used the human capital method that decomposes costs into direct categories such as medical and insurance administration expenses as well as indirect categories such as lost earnings, lost home production, and lost fringe benefits. Some cost estimates were drawn from the literature while others were generated within this study. Total costs were calculated by multiplying average costs by the number of injuries and illnesses in each diagnostic category. RESULTS: Approximately 6500 job-related deaths from injury, 13.2 million nonfatal injuries, 60,300 deaths from disease, and 862,200 illnesses are estimated to occur annually in the civilian American workforce. The total direct ($65 billion) plus indirect ($106 billion) costs were estimated to be $171 billion. Injuries cost $145 billion and illnesses $26 billion. These estimates are likely to be low, because they ignore costs associated with pain and suffering as well as those of within-home care provided by family members, and because the numbers of occupational injuries and illnesses are likely to be undercounted. CONCLUSIONS: The costs of occupational injuries and illnesses are high, in sharp contrast to the limited public attention and societal resources devoted to their prevention and amelioration. Occupational injuries and illnesses are an insufficiently appreciated contributor to the total burden of health care costs in the United States.

Accidents, Occupational↗

PubMed1997

Rapid analysis for the isolation of novel genes encoding putative effectors to the position-specific regulatory element of murine Hoxa-7.

Hox genes are known to play a critical role in pattern formation during vertebrate development by being expressed at the specific time and in the specific position along the antero-posterior body axis. In order to understand the regulatory mechanism for the position-specific expression of murine Hoxa-7, yeast one-hybrid system was applied. DNA fragment conferring a position specificity to the Hoxa-7 gene was placed just upstream from the yeast CYC1 promoter and lacZ gene in a reporter. Selection of LacZ positive clones after cotransformation of the reporter and mouse embryonic cDNA library as an effector, which was designed to be expressed as fusion proteins to the GAL4 activation domain, allowed us to isolate putative factors interacting with the position-specific regulatory element of murine Hoxa-7. A total of 28 positive clones were screened from 5 x 10(5) yeast transformants. About 70% of the clones turned out to be novel and most of the candidate clones selected in this study showed a temporally restricted expression pattern during embryonic development, suggesting that this method could provide an efficient way for isolating novel genes whose expressions are temporally regulated during embryogenesis.

Animals↗